Devices and methods for cardiovascular reflex control

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DESCRIPTION

Devices for cardiovascular reflex control.

Field of the invention

The present invention generally relates to medical devices and methods for use in the treatment and / or management of cardiovascular and renal disorders. Specifically, the present invention relates to devices and methods for controlling the baroreflex system for the treatment and / or management of cardiovascular and renal disorders and their underlying causes and conditions.

Background of the invention

Cardiovascular disease is a major contributor to patient illness and mortality. It is also a primary cause of health care spending, costing more than $ 326 billion each year in the United States. Hypertension, or high blood pressure, is a major cardiovascular disorder estimated to affect more than 50 million people in the United States alone. Of these with hypertension, less than 30% are reported to have their blood pressure under control. Hypertension is a leading cause of heart attack and failure. It is the primary cause of death in more than 42,000 patients a year and is listed as a primary or contributing cause of death in more than 200,000 patients a year in the United States. According to the above, hypertension is a serious health problem that requires significant research and development for its treatment.

Hypertension can occur when the body's smallest blood vessels (arterioles) become constricted, causing an increase in blood pressure. Because the blood vessels constrict, the heart must work harder to keep the blood flowing at higher pressures. Although the body can tolerate short periods of increased blood pressure, sustained hypertension can eventually result in damage to multiple organs in the body, including the kidneys, brain, eyes, and other tissues, causing a wide variety of diseases associated with it. High blood pressure can also damage the lining of the blood vessels, speeding up the process of arteriosclerosis and increasing the likelihood that a blood clot can develop. This could lead to a heart attack and / or heart attack. Sustained high blood pressure can eventually result in an enlarged and deteriorating heart (hypertrophy) which can lead to heart failure.

Heart failure is the ultimate common expression of a variety of cardiovascular disorders, including ischemic heart disease. It is characterized by the inability of the heart to pump enough blood to meet the body's needs resulting in fatigue, reduced capacity for exercise, and poor survival. An estimated 5,000,000 people in the United States suffer from heart failure, leading directly to 39,000 deaths per year and contributing to another 225,000 deaths per year. It is also estimated that more than 400,000 new cases of heart failure are diagnosed each year. Heart failure accounts for more than 900,000 hospital admissions annually, and is the most common discharge diagnosis in patients over 65 years of age. The cost of treating heart failure in the United States has been reported to exceed $ 20 billion annually. According to the above, heart failure is also a serious health problem that requires significant research and development for its treatment and / or management.

Heart failure results in the activation of a number of body systems to compensate for the inability of the heart to pump enough blood. Many of these responses are mediated by an increase in the level of activation of the sympathetic nervous system, as well as the activation of multiple other neurohormonal responses. Generally speaking, this activation of the sympathetic nervous system signals the heart to increase cardiac rate and force of contraction to increase cardiac output. It tells the kidneys to expand blood volume by retaining sodium and water; and signals the arterioles to constrict to raise blood pressure. Cardiac, renal, and vascular responses increase the workload of the heart further accelerating myocardial damage and exacerbating the state of heart failure. Accordingly, it is desirable to reduce the level of activation of the sympathetic nervous system in order to stop or at least minimize this vicious cycle and therefore treat or manage heart failure.

A number of drug treatments have been proposed for the management of hypertension, heart failure, and other cardiovascular disorders. They include vasodilators to lower blood pressure and ease the workload of the heart, diuretics to reduce fluid overload, inhibitors and blockers of the body's neurohormonal responses, and other medications.

Various surgical procedures have been proposed for these diseases. For example, heart transplantation has been proposed for patients suffering from severe refractory heart failure. Alternatively, an implantable medical device such as a ventricular assist device (VAD) can be implanted in the chest to increase the pumping action of the heart. Alternatively, an intra-aortic balloon pump can be used to maintain heart function for short periods of time, but typically no longer than a month. Other surgical procedures are also available.

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The carotid sinus wall, a structure at the bifurcation of the common carotid arteries, has been known for decades to contain stress receptors (baroreceptors) that are sensitive to blood pressure. These receptors send signals through the carotid sinus nerve to the brain, which in turn regulates the cardiovascular system to maintain normal blood pressure (the baroreflex), in part through activation of the sympathetic nervous system. Electrical stimulation of the carotid sinus nerve (baromarker) has previously been proposed to reduce blood pressure and the workload of the heart in the treatment of elevated blood pressure and angina. For example, US Patent No. 6,073,048 to Kieval et al. describes a baroreflex modulation system and a method for stimulating the baroreflex arc based on various cardiovascular and pulmonary parameters.

Although each of these alternatives provides benefits in some way, each of the therapies has its own disadvantages. For example, drug therapy is often incompletely effective. Some patients may not respond (refractory) to medical therapy. Drugs frequently have unwanted side effects and may need to be administered in complex regimens. These and other factors contribute to poor patient compliance with medical therapy. Drug therapy can also be expensive, adding to health care costs associated with these disorders. In the same way, surgical attempts are very expensive, may be associated with significant patient morbidity and mortality, and may not alter the natural history of the disease. Baromarkers have not gained acceptance, either. Various problems with electrical stimulation of the carotid sinus nerve have been reported in the medical literature. These include invasive surgical procedure to implant nerve electrodes, and postoperative pain in the jaw, throat, face, and head during stimulation. In addition, it has been noted that high voltages that are sometimes required for nerve stimulation can damage the nerves of the carotid sinus. In accordance with the foregoing, there continues to be a substantial and long felt need for new devices and methods for treating and / or managing high blood pressure, heart failure, and their associated cardiovascular and nervous system disorders.

Situations may arise in which raising a patient's blood pressure is beneficial. For example, the patient may be experiencing a period of reduced blood pressure, or hypotension. Conditions associated with symptomatic hypotension include vasovagal reactions, orthostatic hypotension, and dysautonomia. Alternatively, it may be advantageous to increase the blood pressure of a patient in whom the blood pressure may be normal or close to normal, for example in claudication syndromes. Therefore, there is also a need for a therapy that can acutely increase a patient's blood pressure.

A first aspect of the invention is defined in claim 1. A second aspect is set out in claim 14. The invention further provides a system as set forth in claim 1.

To attack hypertension, heart failure, and their associated cardiovascular and nervous system disorders, a number of devices, systems, and methods are described by which blood pressure, nervous system activity, and neurohormonal activity can be regulated in such a manner. selective and controllable activating baroreceptors. Through selective and controlled activation of baroreceptors, it is possible to reduce excessive blood pressure, activation of the sympathetic nervous system, and neurohormonal activation, thereby minimizing their deleterious effects on the heart, bascular system, and other organs and tissues.

Systems and methods are described for treating a patient by inducing a baroreceptor signal to affect a change in the baroreflex system (eg, reduced cardiac rate, reduced blood pressure, etc.). The baroreceptor signal is activated or modified in some other way by selectively activating the baroreceptors. To accomplish this, the disclosed system and methods utilize a baroreceptor activation device positioned close to a baroreceptor in the carotid sinus, aortic arch, heart, common carotid arteries, subclavian arteries, and / or bracheocephalic artery. According to the invention, the baroreceptor activation device is located in the right and / or left carotid sinus (near the bifurcation of the common carotid artery) and / or the aortic arch. The present invention is described with reference to the location in the carotid sinus.

Generally speaking, the baroreceptor activation device can be activated, deactivated, or otherwise modulated to activate one or more baroreceptors and induce a baroreceptor signal or a change in the baroreceptor signal to thereby affect a change in the system. baroreflex. The baroreceptor activation device can be activated, deactivated, or otherwise modulated continuously, periodically, or by episodes. The baroreceptor activation device can comprise a wide variety of devices that use mechanical, electrical, thermal, chemical, biological, or other means to activate the baroreceptor. The baroreceptor can be activated directly, or activated indirectly through adjacent vascular tissue. The baroreceptor activation device can be positioned within the vascular lumen (eg, intravascularly), outside the vascular wall (eg, extravascularly), or within the vascular wall (eg, intramurally). To maximize therapeutic efficacy, a mapping method can be employed to precisely locate or position the baroreceptor activation device.

The embodiments use electrical means to activate the receiver, and various electrode designs are provided. Electrode designs are particularly suitable for connection to the carotid arteries in or near the carotid sinus, and can be designed to minimize extraneous tissue stimulation.

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A control system can be used to generate a control signal that activates, deactivates or otherwise modulates the activation device of the baroreceptor. The control system can operate in an open circuit mode or in a closed circuit mode. For example, in open circuit mode, the patient and / or physician can directly or remotely interface with the control system to prescribe the control signal. In closed-loop mode, the control signal can be a response to feedback from a sensor, where the response is dictated by a predefined or programmable algorithm that defines a stimulus regime.

The stimulus regimen is preferably selected to promote long-term efficacy and to minimize power requirements. It is theorized that uninterrupted activation of baroreceptors may result in less responsive baroreceptors and / or the baroreflex system over time, thereby decreasing the effectiveness of therapy. Therefore, the stimulus regimen can be selected to modulate, for example, the baroreceptor activation device in such a way that the baroreceptors maintain their responsiveness over time. Specific examples of stimulus regimens that promote long-term efficacy are described in more detail below.

To attack low pressure and other conditions that require increased blood pressure, the present invention provides a number of devices, systems, and methods by which blood pressure can be selectively and controllably regulated by inhibiting or damping signals from the blood pressure. baroreceptor. By selectively and controllably inhibiting or damping baroreceptor signals, we describe how to reduce the conditions associated with low blood pressure.

Brief description of the drawings

Figure 1 is a schematic illustration of the upper torso of a human body showing the major arteries and veins and associated anatomy;

Figure 2A is a cross-sectional schematic illustration of the carotid sinus and baroreceptors within the vascular wall;

Figure 2B is a schematic illustration of the baroreceptors within the vascular wall and the baroreflex system;

Figure 3 is a schematic illustration of a baroreceptor activation system;

Figures 4A and 4B are schematic illustrations of a baroreceptor activation device in the form of an internal inflatable balloon that mechanically induces a baroreceptor signal;

Figures 5A and 5B are schematic illustrations of a baroreceptor activation device in the form of an external pressure cuff that mechanically induces a baroreceptor signal;

Figures 6A and 6B are schematic illustrations of a baroreceptor activation device in the form of an internal deformable wire frame that mechanically induces a baroreceptor signal;

Figures 6C and 6D are cross-sectional views of alternate embodiments of the wire member illustrated in Figures 6A and 6B;

Figures 7A and 7B are schematic illustrations of a baroreceptor activation device in the form of a deformable wire frame that mechanically induces a baroreceptor signal;

Figures 7C and 7D are cross-sectional views of alternative arrangements of the wire member illustrated in Figures 7A and 7B;

Figures 8A and 8B are schematic illustrations of a baroreceptor activation device in the form of an external flow regulator that artificially creates back pressure to induce a baroreceptor signal;

Figures 9A and 9B are schematic illustrations of a baroreceptor activation device in the form of an internal flow regulator that artificially creates back pressure to induce a baroreceptor signal;

Figures 10A and 10B are schematic illustrations of a baroreceptor activation device in the form of a magnetic device, which mechanically induces a baroreceptor signal;

Figures 11A and 11B are schematic illustrations of a baroreceptor triggering device in the form of a transducer that mechanically induces a baroreceptor signal;

Figures 12A and 12B are schematic illustrations of a baroreceptor activation device in the form of a fluid delivery device which can be used to deliver an agent that chemically or biologically induces a baroreceptor signal;

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Figures 13A and 13B are schematic illustrations of a baroreceptor activation device in the form of an internal conductive structure which electrically or thermally induces a baroreceptor signal;

Figures 14A and 14B are schematic illustrations of a baroreceptor activation device in the form of an internal conductive structure, activated by an internal inductor, which electrically or thermally induces a baroreceptor signal;

Figures 15A and 15B are schematic illustrations of a baroreceptor activation device in the form of an internal conductive structure, activated by an internal inductor located in an adjacent vessel, which electrically or thermally induces a baroreceptor signal;

Figures 16A and 16B are schematic illustrations of a baroreceptor activation device in the form of an internal conductive structure, activated by an external inductor, which electrically or thermally induces a signal from a baroreceptor;

Figures 17A and 17B are schematic illustrations of a baroreceptor activation device in the form of an external conductive structure which electrically or thermally induces a baroreceptor signal;

Figures 18A and 18B are schematic illustrations of a baroreceptor activation device in the form of an internal bipolar conductive structure which electrically or thermally induces a baroreceptor signal;

Figures 19A and 19B are schematic illustrations of a baroreceptor activation device in the form of an electromagnetic field response device that electrically or thermally induces a baroreceptor signal;

Figures 20A and 20B are schematic illustrations of a baroreceptor activation device in the form of an external Peltier device which thermally induces a baroreceptor signal;

Figures 21A - 21C are schematic illustrations of a preferred arrangement of an inductively activated electrically conductive structure;

Figures 22A-22F are schematic illustrations of various possible electrode arrangements around the carotid sinus for extravascular electrical activation;

Figure 23 is a schematic illustration of a serpentine-shaped electrode for extravascular electrical activation;

Figure 24 is a schematic illustration of a plurality of electrodes aligned orthogonal to the direction of wrapping around the carotid sinus for extravascular electrical activation;

Figures 25-28 are schematic illustrations of various multichannel electrodes for extravascular electrical activation;

Figure 29 is a schematic illustration of an extravascular electrical activation device including a tether and anchor disposed around the carotid sinus and common carotid artery;

Figure 30 is a schematic illustration of an alternative extravascular electrical actuator including a plurality of fins and a spine;

Figure 31 is a schematic illustration of an electrode arrangement for extravascular electrical activation;

Figure 32 is a schematic illustration of an alternative lead fragment for use with an electrode device such as that shown in Figure 31;

Figure 33 is a schematic illustration of the right carotid artery showing a bulge in the vascular wall which is a typical carotid sinus marking;

Figure 34 is a schematic illustration of a baroreceptor activation device disposed around the carotid artery which can be used to map the baroreceptors therein;

Figure 35 is a schematic cross-sectional view taken along line 35-35 in Figure 34, showing a mapping coordinate system for the left and right carotid arteries;

Figures 36 and 37 are graphs illustrating the variability of the baroreceptor response around the right and left carotid arteries respectively;

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Figure 38 illustrates a blood pressure signal, an ECG signal, and a control / output signal as a function of time; Y

Figures 39-41 are various graphs illustrating the effectiveness of various stimulus regimes.

Detailed description of the invention

The following detailed description of the invention should be read with reference to the drawings in which similar elements in the different drawings are numbered in the same way. The drawings, which are not necessarily to scale, are only illustrative.

To better understand the invention, it may be useful to explain some part of the basic vascular anatomy associated with the cardiovascular system. With reference to Figure 1 which is a schematic illustration of the upper torso of a human body 10 showing some of the major arteries and veins of the cardiovascular system. The left ventricle of the heart 11 pumps oxygenated blood to the aortic arch 12. The right subclavian artery 13, the right common carotid artery 14, the left common carotid artery 15 and the left subclavian artery 16 branch from the aortic arch 12 proximal to the descending thoracic aorta 17. Although relatively short, a distinguishable vascular segment called bracheocephalic artery 22 connects the right subclavian artery 13 and the right common carotid artery 14 to the aortic arch 12. The right carotid artery 14 branches into the right external carotid artery 18 and the right internal carotid artery 19 into the right carotid sinus 20. Although not shown for clarity purposes only, the left carotid artery 15 branches similarly in the external carotid artery and the left internal carotid artery in the left carotid sinus.

From the aortic arch 12, oxygenated blood flows into the carotid arteries 18/19 and the subclavian arteries 13/16. From the carotid artery 18/19, oxygenated blood circulates through the head and cerebral vasculation and oxygen-depleted blood returns to the heart 11 through the jugular veins, of which only the right internal jugular vein 27 is shown by clarity purposes. From the subclavian arteries 13/16, oxygenated blood circulates through the superior peripheral vasculation and oxygen-depleted blood returns to the heart via the subclavian veins, of which only the right subclavian vein 23 is shown, also for purposes of clarity. The heart 11 pumps oxygen-depleted blood through the pulmonary system where it is reoxygenated. The reoxygenated blood returns to the heart 11 which pumps the reoxygenated blood into the aortic arch as described above, and the cycle repeats.

Within the arterial walls of the aortic arch 12, the common carotid arteries 14/15 (near the right carotid sinus 20 and the left carotid sinus), the subclavian artery 13/16, and the bracheocephalic artery 22 are the 30 baroreceptors. For example, as best seen in Figure 2A, baroreceptors 30 reside within the vascular walls of the carotid sinus 20. Baroreceptors 30 are a type of strain receptor used by the body to sense blood pressure. An increase in blood pressure causes the arterial wall to stretch, and a decrease in blood pressure causes the arterial wall to return to its original size. Such a cycle is repeated with each beat of the heart. Since the baroreceptors 30 are located within the arterial wall, they are able to sense the deformation of the adjacent tissue, which is indicative of a change in blood pressure. Baroreceptors 30 located in the right carotid sinus 20, the left carotid sinus, and the aortic arch 12 play the most significant role in detecting the blood pressure that affects the baroreflex system 50, which is described in more detail with reference to Figure 2B. .

Reference is now made to Figure 2B, which shows a schematic illustration of baroreceptors 30 arranged in a generic vascular wall 40 and a schematic flow diagram of the baroreflex system 50. The baroreceptors 30 are profusely distributed within the arterial walls 40 of the vessels. main arteries previously described, and generally form a tree 32. Baroreceptor shaft 32 comprises a plurality of baroreceptors 30, each of which transmits signals from the baroreceptor to brain 52 via nerve 38. Baroreceptors 30 are so profusely distributed and arboreal within vascular wall 40 that discrete baroreceptor trees 32 they are not easily discernible. At this point, those skilled in the art will appreciate that the baroreceptors 30 shown in Figure 2B are primarily schematic for purposes of illustration and discussion.

The signals from the baroreceptors are used to activate a number of body systems that collectively can be referred to as the baroreflex system 50. The baroreceptors 30 are connected to the brain 52 through the nervous system 51. Thus, the brain 52 is capable of detecting changes in blood pressure, which is indicative of cardiac output. If the cardiac output is insufficient to meet the demand (that is, the heart 11 is unable to pump enough blood), the baroreflex system 50 activates a number of body systems, including the heart 11, kidneys 53, vessels 54 and other organs. / fabrics. Such activation of the baroreflex system 50 generally corresponds to an increase in neurohormonal activity. Specifically, the baroreflex system 50 initiates a neurohormonal sequence that signals the heart 11 to increase cardiac rate and increase force in order to increase cardiac output, signals the kidneys 53 to increase blood volume by retaining sodium and water, and indicates to vessels 54 which are constricted to raise blood pressure. Cardiac, renal, and vascular responses increase blood pressure and cardiac output 55 and thus increase the workload of the heart. In a patient with heart failure, this further accelerates myocardial damage and exacerbates the heart failure state.

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To attack the problems of hypertension, heart failure, other cardiovascular disorders and kidney disorders, a number of devices, systems and methods are described by which the baroreflex system 50 is activated to reduce excessive blood pressure, the activity of the autonomic nervous system. and neurohormonal activation. In particular, a number of devices, systems and methods are described by which the baroreceptors 30 can be activated, thereby indicating an increase in blood pressure and directing the brain 52 to reduce the body's blood pressure and blood level. sympathetic nervous system and neurohormonal activation, and increase the activation of the parasympathetic nervous system, thus having a beneficial effect on the cardiovascular system and other body systems.

Referring to Figure 3, a system is generally provided that includes a control system 60, a baroreceptor activation device 70, and a sensor 80 (optional), which generally operate as follows. Sensor 80 senses and / or monitors a parameter (eg, cardiovascular function) indicative of the need to modify the baroreflex system and generates a signal indicative of the parameter. The control system 60 generates a control signal as a function of the received sensor signal. The control signal activates, deactivates, or otherwise modulates the baroreceptor activation device 70. Typically, activation of device 70 results in activation of baroreceptors 30. Alternatively, deactivation or modulation of baroreceptor activation device 70 may cause modification of the activation of baroreceptors 30. The baroreceptor activation device 70 can comprise a wide variety of devices that use mechanical, electrical, thermal, chemical, biological, or other means to activate the baroreceptors 30. Thus, when sensor 80 detects a parameter indicative of the need to modify the activity of the baroreflex system (eg, excessive blood pressure), control system 60 generates a control signal to modulate (eg, activate) the monitoring device. activation 70 of the baroreceptor thereby inducing a baroreceptor signal 30 that is sensed by the brain 52 to make excessive blood pressure evident. When sensor 80 detects a parameter indicative of normal body function (eg, normal blood pressure), control system 60 generates a control signal to modulate (eg, deactivate) baroreceptor activation device 70.

As mentioned above, the baroreceptor activation device 70 can comprise a wide variety of devices that utilize mechanical, electrical, thermal, chemical, biological, or other means to activate the baroreceptors 30. Specific examples of the generic baroreceptor activation device 70 are discussed with reference to Figures 4-21. In most cases, particularly the mechanical activation illustrations, the baroreceptor activation device 70 indirectly activates one or more baroreceptors 30 by stretching or deforming the vascular walls 40 that surround the baroreceptors 30. In some other instances, particularly non-mechanical activation examples, the baroreceptor activation device 70 can directly activate one or more baroreceptors 30 by changing the electrical, thermal or chemical environment or potential across the baroreceptors 30. It is also possible that changing the electrical, thermal, or chemical potential across the tissue surrounding the baroreceptors 30 may cause the surrounding tissue to stretch or otherwise deform, thereby mechanically activating the baroreceptors 30. In other cases, particularly of biological activation, a change in the function or sensitivity of the baroreceptors 30 can be induced by changing the biological activity in the baroreceptors 30 and altering their intracellular flattening and function.

All specific embodiments of the baroreceptor activation device 70 are suitable for implantation, and are preferably implanted using a percutaneous minimally invasive translumenal approach and / or a minimally invasive surgical approach, depending on whether device 70 is disposed intravascularly, extravascularly, or within vascular wall 40. The baroreceptor activation device 70 can be positioned anywhere in the baroreceptors 30 that affect the baroreflex system 50 which are numerous, such as in the heart 11, in the aortic arch 12, in the common carotid arteries 18/19 near the carotid sinus 20, in the subclavian arteries 13/16 or in the bracheocephalic artery 22. The baroreceptor activation device 70 can be implanted such that the device 70 is positioned immediately adjacent to the baroreceptors 30. Alternatively, the baroreceptor activation device 70 can be outside the body such that the device 70 is positioned at a short distance but close to the baroreceptors 30. Preferably, the baroreceptor activation device 70 is implanted near the right carotid sinus 20 and / or the left carotid sinus (near the bifurcation of the common carotid artery) and / or the aortic arch 12, where the baroreceptors 30 impact significant in the baroreflex system 50. For purposes of illustration only, the present invention is described with reference to the baroreceptor activation device 70 positioned near the carotid sinus 20.

Optional sensor 80 is operatively coupled to control system 60 via electrical sensor wire 82. Sensor 80 may comprise any suitable device that measures or monitors a parameter indicative of the need to modify the activity of the baroreflex system. For example, sensor 80 may comprise a physiological meter or transducer that measures ECG, blood pressure (systolic, diastolic, average, or pulse pressure), blood volume flow rate, blood flow rate, blood pH, O content.₂ or CO₂, mixed venous oxygen saturation (SVO₂), vasoactivity, nerve activity, tissue activity or composition. Examples of suitable transducers or meters for sensor 80 include ECG electrodes, a piezoelectric pressure transducer, an ultrasonic flow rate transducer, an ultrasonic volumetric flow rate transducer, a thermodilusion flow rate transducer, a pressure transducer by capacitance, a membrane pH electrode, an optical detector (SVO2) or a strain gauge. Although only sensor 80 is shown, multiple sensors 80 of the same or different types at the same or different locations may be used.

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Sensor 80 is preferably positioned in a heart chamber 80, or in / on a major artery such as the aortic arch 12, a common carotid artery 14/15, a subclavian artery 13/16, or the bracheocephalic artery 22, in such a way that the parameter of interest can be easily established. Sensor 80 may be disposed within the body such as in or on an artery, vein, or nerve (eg, the vagus nerve) or disposed outside the body, depending on the type of transducer or meter used. Sensor 80 may be separate from or combined with baroreceptor triggering device 70. For illustration purposes only, sensor 80 is shown positioned over the right subclavian artery 13.

By way of example, control system 60 includes a control block 61 comprising a processor 63 and memory 62. Control system 60 is connected to sensor 80 via sensor cable 82. Control system 60 is also connected to sensor 80. connected to the activation device 70 of the baroreceptor by means of an electrical control cable 72. Thus, the control system 60 receives a sensor signal from the sensor 80 via a sensor cable 82, and transmits a control signal to the baroreceptor activator 70 via a control cable 72.

Memory 62 can contain data related to the sensor signal, control signal, and / or values ​​and commands provided by input device 64. Memory 62 can also include software that contains one or more algorithms that define one or more functions. or relationships between the control signal and the sensor signal. The algorithm can dictate on or off control signals depending on the sensor signal or a mathematical derivative thereof. The algorithm can dictate an on or off control signal when the sensor signal falls below a predetermined lower threshold value, rises above a predetermined upper threshold value, or when the sensor signal indicates a physiological event. specific.

As previously mentioned, the baroreceptor activation device 70 can activate the baroreceptors 30 mechanically, electrically, thermally, chemically, biologically, or in other ways. In some cases, the control system 60 includes a driver 66 to provide the desired power mode for the baroreceptor activation device 70. For example, if the baroreceptor activation device 70 uses pneumatic or hydraulic actuation, the driver 66 may comprise a pressure / vacuum source and the cable 72 may comprise fluid lines. If the baroreceptor activation device 70 uses electrical or thermal actuation, the pulse cable 66 may comprise a power amplifier or the like and the cable 72 may comprise electrical wires. If the baroreceptor activation device 70 utilizes chemical or biological actuation, the impeller 66 may comprise a fluid reservoir and a pressure / vacuum source and the lead 72 may comprise a fluid line. In other cases, driver 66 may not be necessary, particularly if processor 63 generates an electrical signal strong enough for low-level electrical or thermal actuation of baroreceptor driver 70.

Control system 60 may operate as a closed loop using feedback from sensor 80, or as an open loop using commands received by input device 64. Open loop operation of control system 60 preferably uses some feedback from transducer 80, but it can also operate without feedback. Commands received by input device 64 can directly influence the control signal or can alter the software and related algorithms contained in memory 62. The patient and / or treating physician can provide commands to input device 64. The Screen 65 can be used to view sensor signal, control signal and / or software / data contained in memory 62. The control signal generated by the control system 60 may be continuous, periodic, episodes, or a combination thereof, as dictated by an algorithm contained in memory 62. The algorithm contained in memory 62 defines a stimulus regime the which dictates the characteristics of the control signal as a function of time, and thus dictates the stimulation of the baroreceptors as a function of time. Continuous control signals include a pulse, a pulse train, a triggered pulse, and a triggered train of pulses, all of which are generated continuously. Examples of periodic control signals include each of the control signals described above that have a designated start time (eg, start every minute, hour, or day) and a designated duration (eg, one second, one minute, one hour). Examples of episode control signals include each of the continuous control signals described above that are triggered by an episode (e.g., trigger by the patient / physician, an increase in blood pressure above a certain threshold, etc. .).

The stimulus regime governed by the control system 60 can be selected to promote long-term efficacy. It is theorized that uninterrupted or otherwise unchanged activation of baroreceptors 30 may result in the baroreceptors and / or the baroreflex system responding less efficiently over time, thereby decreasing the long-term effectiveness of the therapy. Therefore, the stimulus regimen can be selected to activate, deactivate, or otherwise modulate the baroreceptor activation device 70 in such a way that therapeutic efficacy is maintained over the long term.

In addition to maintaining therapeutic efficacy over time, the stimulus regimens of the present invention can be selected by reducing the power requirements / consumption of the system 60. As will be described in more detail below, the stimulus regimen may dictate that the baroreceptor activation device 70 be activated initially at a relatively higher energy and / or power level, and subsequently activated at a higher energy level. and / or relatively lower power. The first level achieves the desired initial therapeutic effect, and the second (lower) level maintains the desired therapeutic effect for a long time. By reducing the level of energy and / or power after the initial desired therapeutic effect is achieved, the power required or consumed by the activation device 70 is also reduced in the long term. This can be correlated to

ES 2 330 833 T3 systems that have greater longevity and / or reduced size (due to reductions in the size of the power source and associated components).

Another advantage of the stimulus regimens described is the reduction of unwanted collateral tissue stimulation. As mentioned above, the stimulus regimen may dictate that the baroreceptor activation device 70 is initially activated with a relatively high energy and / or power level to achieve the desired effect, and subsequently activated at a relatively high energy level and / or power. / or relatively low power to maintain the desired effect. By reducing the level of energy and / or power output, the stimulus may not travel as far from the target site, thereby reducing the likelihood that adjacent tissues such as the muscles of the neck and head will be inadvertently stimulated.

Such style regimes can be applied to all of the baroreceptor activation devices described herein. In addition to baroreceptor activation devices 70, such stimulation regimes can be applied to stimulation of carotid sinus nerves or other nerves that affect the baroreflex system. In particular, the stimulus regimes described here can be applied to the baromacemaker (that is, electrical stimulation of the carotid sinus nerve), which has been proposed to reduce blood pressure and the workload of the heart in the treatment of blood pressure. discharge and angina. For example, the stimulus regimes of the present invention can be applied to the baromacemaker system described in US Patent No. 6,073,048 to Kieval et al.

The stimulus regimen can be described in terms of the control signal and / or the output signal of the baroreceptor trigger 70. Generally speaking, changes in the control signal result in corresponding changes in the output of the baroreceptor activation device 70 which affects corresponding changes in the baroreceptors 30. The correlation between changes in the control signal and changes in the baroreceptor activation device 70 may be proportional or non-proportional, direct or indirect (inverse), or any other known or predictable mathematical relationship. For purposes of illustration only, the stimulus regimen can be described herein in such a way as to assume that the output of the baroreceptor activation device 70 is directly proportional to the control signal.

A first general approach to a stimulus regimen that promotes long-term efficacy and reduces power requirements / consumption involves the generation of a control signal that causes the baroreceptor activation device 70 to have a first output level of relatively high energy and / or power, and subsequently change the control signal to cause the baroreceptor driver 70 to have a relatively lower second energy and / or power output level. The first output level can be selected and maintained long enough to achieve the desired initial effect (for example, a reduction in heart rate and / or blood pressure), after which the output level can be reduced to the second. level long enough to maintain the desired effect for the desired period of time.

For example, if the first output level has a power and / or energy value of X₃, the second output level may have a power and / or energy value of X₂, where X₂ is less than X₃. In some cases, X₂ it can be equal to 0, so that the first level is "on" and the second level is "off". It is recognized that power and energy refer to two different parameters, but can, in at least some context, be used interchangeably. Generally speaking, power is a time derivative of energy. Thus, in some cases, a change in one of the parameters (power or energy) may not correlate to the same or similar change in the other parameter. It is contemplated that a change in one or both of the parameters may be adequate to obtain the desired result of promoting long-term efficacy.

It is also contemplated that more than two levels may be used. Each level can additionally increase the energy or power output to achieve the desired effect or decrease the energy or power output to retain the desired effect. For example, in some cases, it may be desirable to have additional reductions in the output level if the desired effect can be sustained at lower power or energy levels. In other cases, particularly when the desired effect is to decrease or is otherwise not sustained, it may be desirable to increase the output level until the desired effect is restored, and subsequently decrease the output level to maintain the effect.

The transition from each level can be a staged function (for example, a single stage or a series of stages), a gradual transition over a period of time, or a combination thereof. Additionally, signal levels can be continuous, periodic, or episodes as previously discussed.

The output level (power or energy) of the baroreceptor activation device 70 can be changed in a number of different ways depending on the activation mode used. For example, in the mechanical activation embodiments described herein, the output level of the baroreceptor activation device 70 can be changed by changing the force / pressure output, tissue travel distance, and / or tissue travel rate. . In the thermal activation embodiments described herein, the output level of the baroreceptor activation device 70 can be changed by changing the temperature, the temperature increase rate, or the temperature decrease rate (dissipation rate). In the chemically and biologically activated embodiments described herein, the output level of the baroreceptor activation device 70 can be changed by changing the volume / concentration of the administered dose and / or the dose delivery rate.

ES 2 330 833 T3

In embodiments with electrical drive using an unmodulated signal, the output level (power or energy) of the baroreceptor drive 70 can be changed by changing the voltage, current, and / or duration of the signal.

The output signal of the baroreceptor activation device 70 may be, for example, constant current or constant voltage. In embodiments with electrical drive using a modulated signal, where the output signal comprises, for example, a series of pulses, various pulse characteristics can be changed individually or in combination to change the power or energy level of the output signal. Such pulse characteristics include, but are not limited to: pulse width (PA), pulse frequency (PF), pulse width or duration (PW), pulse waveform (square, triangle, sinusoidal, etc.) , pulse polarity (for bipolar electrodes) and pulse phase (monophasic, biphasic).

In electrically actuated embodiments where the output signal comprises a pulse train, various other signal characteristics can be changed in addition to the pulse characteristics described above. As illustrated in Figure 38, the control or output signal 410 may comprise a pulse train 412 that generally includes a series of pulses 414 that are presented in pulses 416. Characteristics of pulse train 412 that can be changed include, but are not limited to: pulse width (equal to pulse width if constant within pulse packet 416), pulse waveform (i.e. variation of the amplitude of the pulse within the pulse packet 416), pulse frequency (BF), and pulse width or duration (BW). Signal 410, or a portion thereof (for example, pulse 416 within pulse train 412), may be triggered by any of the events previously discussed, or by a particular portion of the blood pressure signal 450 or the signal ECG 460 (for example, R wave is shown in Figure 38), or other physiological indicator of time. If signal 410 or a portion thereof is triggered, the trigger event can be changed and / or the delay of the trigger event can be changed.

A second general approach for a stimulus regimen that promotes long-term efficacy and reduces power requirements / consumption involves the use of a baroreceptor activation device 70 that utilizes multiple output means (eg, electrodes) or the use of of multiple baroreceptor activation devices 70 having single or multiple output means. Basically, the stimulation regimen according to this approach requires an alternate activation of two or more devices 70 or means of exit, which are positioned in different anatomical locations. The activation of the alternation can be achieved by alternating the control signal between the devices or the output means. As used in this context, toggle activation includes switching between individual output means, switching between sets of output means and individual output means, and switching between different sets of output means. By alternating activation between two or more different anatomical sites, the exposure of any single anatomic site to an output signal is reduced.

More specifically, a first device 70 or outlet means may be connected to a first baroreceptor location, and a second device 70 or outlet means may be connected to a second baroreceptor location, where the first location is different from the second location. , and the control signal alternates upon activation of the first and second output devices or means. Although described with reference to the two (first and second) devices 70 or output means, more than two may be used. By way of example, not limitation, a first outlet device 70 or means can be connected to the right carotid sinus, and a second outlet device 70 or means can be connected to the left carotid sinus. Alternatively, a first outlet device 70 or means can be connected to the left internal carotid artery and a second outlet device 70 or means can be connected to the right internal carotid artery. As yet another alternative, the first and second output devices 70 or means may be arranged next to each other but separated by a small distance (eg, electrodes with multiple points of contact). In each instance, the control signal alternates the activation of the first and second output devices or means to reduce the exposure of the signal for each anatomical location. Those skilled in the relevant art will recognize that there are many possible anatomical combinations within the scope of this embodiment that are not specifically mentioned herein for the sake of simplicity only.

A third general modality for a stimulus regimen that promotes long-term efficacy and reduces power requirements / consumption involves changing the domain characteristics over time and / or the characteristics of the therapy trigger events. For example, a periodic control signal that has a designated start time (for example, start every minute, hour, or day; specific time of day) and a designated duration (for example, one second , one minute, one hour) can have a change in designated start time and / or duration. Alternatively, an episode control signal that is triggered by an episode (e.g. patient / physician activation, a particular part of the ECG signal, an increase in blood pressure above a certain threshold, specific time of day, etc.) may have a change in the delay from the trigger event or a change in the trigger event itself. For the latter alternative, the trigger event can be provided by a feedback control using sensor 80. As a further alternative, the control signal can be asynchronous, where the start time, duration or delay of a baseline event is asynchronous (for example, random).

Any of the above modalities can be used alone or in combination. The use of a combination of modalities can further promote long-term efficiency and can further reduce power requirements / consumption.

ES 2 330 833 T3

To demonstrate the effectiveness of this first modality described above, an animal experiment was carried out using a baroreceptor activation device 70 in the form of an extravascular electrical activation device applied bilaterally (right and left) to the carotid sinus 20. The result of this experiment is illustrated in Figure 39, which shows the control signal (volts) 410, the heart rate (beats per minute) 420, the mean arterial pressure (mmHg) 430 and the arterial pressure (mmHg) 440 on a graph as a function of time. Control signal 410 comprised a pulse train having a pulse width of 2.5 volts, an initial pulse width or duration of 1.0 milliseconds, and a pulse frequency of 100 Hz applied during a first period 401 of approximately 4 minutes. During this first period 401, blood pressure 430/440 and heart rate 420 were significantly reduced. Subsequently, the pulse duration was changed to 0.25 milliseconds and applied for a 402 second period of approximately 2 minutes, while the other parameters remained unchanged. During this second period 402, the reduced blood pressure 430/440 and the heart rate 420 were maintained. After the second period 402, the pulse train was turned off for a period of time 403. During this third period 403, blood pressure 430/440 and heart rate 420 began to gradually rise to their pre-test values. This stimulation regimen demonstrated that the desired therapeutic effect can be maintained after reducing the pulse width of the stimulus device.

Another demonstration of the effectiveness of this first modality is illustrated in Figure 40, which shows the results of an animal experiment using a baroreceptor activation device 70 in the form of a bilaterally applied extravascular electrical activation device (right and left) to the carotid sinus 20. Figure 40 shows the control / output signal (volts) 410, heart rate (beats per minute) 420, mean arterial pressure (mmHg) 430, and arterial blood pressure (mmHg) 440 graphically as a function of time. Control signal 410 comprised a pulse train having a pulse width of 2.5 volts, a pulse duration of 1.0 milliseconds, and an initial pulse frequency of 100 Hz applied during a first period 401 of approximately one minute. During this first period 401, heart rate 420 and blood pressure 430/440 were significantly reduced. The control signal 410 was switched to a pulse frequency of 10 Hz, while the pulse width and duration remained unchanged, during a second period 402 of approximately 4 minutes. During this second period 402, the reduced heart rate and blood pressure were substantially maintained. The control signal 410 was changed back to a pulse frequency of 100 Hz, while the pulse width and duration remained unchanged, for a third period 403 of approximately 40 seconds. During this third period 403, heart rate 420 and blood pressure 430/440 were further reduced. The control signal 410 was changed back to a pulse frequency of 10 Hz, while the pulse width and duration remained unchanged, for a fourth period 404 of approximately 1.5 minutes. During this fourth period 404, the reduced heart rate 420 and the blood pressure 430/440 were substantially maintained. After the fourth period 404, the pulse train was disconnected for a fifth period of time 405. During this fifth time period 405, blood pressure 430/440 and heart rate 420 began to gradually increase to their pre-test values.

A demonstration of the effectiveness of the second modality is illustrated in Figure 41, which shows the results of an animal experiment where a baroreceptor activation device 70 in the form of an extravascular activation device with electrodes was used. A first electrode was connected to the right carotid sinus and a second electrode was connected to the left carotid sinus. Figure 41 shows the control signal (volts) 410, the heart rate (beats per minute) 420, the average blood pressure (mmHg) 430 and the blood pressure (mmHg) 440 on a graph as a function of time. The control / output signal 410 comprised a pulse train having a pulse width of 4.0 volts, a pulse duration of 1.0 milliseconds, and a pulse frequency of 100 Hz applied for a period of 60 seconds 406 left side. During this period 406, heart rate 420 and blood pressure 430/440 were significantly reduced. Control signal 410 was switched to the right side for a period 408 of 60 seconds, while keeping the heart rate and blood pressure low. Control signal 410 was switched between the left and right sides for a total period of 10.5 minutes during which the reduced heart rate and blood pressure were substantially maintained. These experiments demonstrate the effectiveness of the general modalities described previously, each of which involves a stimulus regimen, in promoting long-term efficacy. These stimulus regimes generally involve reducing the output level of the baroreceptor activation device after the initial desired effect is established (first modality), alternating activation between two or more output devices or means positioned in different anatomical locations. (second modality), and / or changing the time domain characteristics and / or the characteristics of the therapy trigger event (third modality). All of these modalities have the common goal of promoting long-term efficacy by maintaining the baroreflex response.

The control system 60 can be implemented in whole or in part. For example, the complete control system 60 can be carried externally by the patient using transdermal connections to sensor cable 82 and control cable 72. Alternatively, control block 61 and driver 66 can be implanted with input device 64 and the screen 65 can be worn externally by the patient using transdermal connections between them. As a further alternative, transdermal connections can be replaced by having transmitters / receivers work together to communicate remotely between components of control system 60 and / or sensor 80 and baroreceptor activator 70.

With general reference to Figures 4-21, schematic illustrations of specific embodiments of the baroreceptor activation device 70 are shown. The design, function and use of these specific modalities, in addition

ES 2 330 833 T3 of control system 60 and sensor 80 (not shown) are the same as described with reference to Figure 3, unless otherwise noted or apparent from the description. Furthermore, the anatomical features illustrated in Figures 4-20 are the same as discussed with reference to Figures 1, 2A and 2B, unless otherwise indicated. In each arrangement, the connections between the 60/70/80 components can be physical (eg, wires, tubes, cables, etc.) or remote (eg, transmitter / receiver, inductive, magnetic, etc.). For physical connections, the connection can travel intra-arterially, intravenously, subcutaneously, or through other natural tissue pathways.

Reference is now made to Figures 4A and 4B which show schematic illustrations of a baroreceptor activation device 100 in the form of an inflatable intravascular balloon. The inflatable balloon device 100 includes a helical balloon 102 that is connected to a fluid line 104. An example of a similar helical balloon is described in U.S. Patent No. 5,181,911 to Shturman, the full disclosure of which is incorporated herein as reference. Balloon 102 preferably has a helical geometry or any other geometry that allows blood perfusion therethrough. Fluid line 104 is connected to driver 66 of control system 60. In this arrangement, driver 60 comprises a pressure / vacuum source (ie, an inflation device) that selectively inflates and deflates helical balloon 102. Upon inflation, helical balloon 102 expands, preferably increasing its outer diameter only, to mechanically activate baroreceptors 30 by stretching or otherwise deforming them and / or vascular wall 40. Upon deflation, helical balloon 102 returns to its relaxed geometry such that the vascular wall 40 returns to its nominal state. Thus, by selectively inflating the helical balloon 102, the baroreceptors 30 adjacent thereto can be selectively activated.

As an alternative to pneumatic or hydraulic expansion using a balloon, a mechanical expansion device (not shown) can be used to expand or dilate vascular wall 40 and thereby mechanically activate baroreceptors 30. For example, the mechanical expansion device may comprise an interwoven tubular wire structure that expands diametrically when longitudinally compressed as described in U.S. Patent No. 5,222,971 to Willard et al. This tubular structure can be intravascularly arranged and allows blood to be perfused through the wire mesh. The driver 66 may comprise a linear actuator connected by actuation cables at opposite ends of the frame. When the opposite ends of the tubular structure are brought closer together by the actuation of the cables, the diameter of the structure increases to expand the vascular wall 40 and activate the baroreceptors 30.

Reference is now made to Figures 5A and 5B which show schematic illustrations of a baroreceptor activation device 120 in the form of an extravascular pressure yoke. The pressure yoke device 120 includes an inflatable yoke 122 that is connected to a fluid line 124. Examples of yokes similar to 122 are described in US Patent No. 4,256,094 to Kapp et al. and United States Patent No. 4,881,939 to Newman, the full disclosures of which are incorporated herein by reference. Fluid line 124 is connected to driver 66 of control system 60. Driver 66 comprises a pressure / vacuum source (ie, an inflatable device), which selectively inflates and deflates yoke 122. Upon inflation, yoke 122 expands, preferably by increasing the internal diameter only, to mechanically activate baroreceptors 30 by stretching or otherwise deforming them and / or vascular wall 40. Upon deflation, yoke 122 returns to its relaxed geometry so so that the vascular wall 40 returns to its nominal state. Thus, by selectively inflating the inflatable yoke 122, the baroreceptors 30 adjacent thereto can be selectively activated.

Impeller 66 can be actuated automatically by control system 60 as discussed above, or it can be actuated manually. An example of an externally actuated pressure / vacuum source is described in US Patent No. 4,709,690 to Haber. Examples of transdermally actuated pressure / vacuum sources are described in U.S. Patent No. 4,586,501 to Claracq, U.S. Patent No. 4,828,544 to Lane et al, and US Patent No. 5,634,878 to Grundei et al.

Those skilled in the art will recognize that other external compression devices can be used in place of the inflatable yoke device 120. For example, a solenoid actuated piston can apply compression to the vascular wall. An example of a solenoid actuated piston device is described in U.S. Patent No. 4,014,318 to Dokum et al, and an example of a hydraulically or pneumatically actuated piston device is described in US Patent No. 4,586,501 to Claracq. Other examples include a rotary ring compression device such as that described in US Patent No. 4,551,862 to Haber, and an electromagnetica lly actuated compression ring device such as that described in US Patent No. 5,509,888 to Haber. Miller.

Reference is now made to Figures 6A and 6B which show schematic illustrations of a baroreceptor activation device 140 in the form of a deformable intravascular framework. The deformable structure device 140 includes a wire, braid, or other graft-like structure 142 disposed in the vascular lumen. The deformable structure 142 includes one or more individual structural members connected to an electrical cable 144. Each of the structural members that forms the deformable structure 142 may comprise a shape memory material 146 (eg, nickel titanium alloy) as illustrated in Figure 6C, or a bimetallic material 148 as illustrated in Figure 6D. Electrical cable 144 is connected to driver 66 of control system 60. Driver 66 comprises a pot generator or amplifier An electrical source that selectively delivers electrical current to structure 142 which resistively heats structural members 146/148. Structure 142

ES 2 330 833 T3 can be unipolar as shown using the surrounding tissue as ground, or bipolar or multipolar using wires connected to each end of structure 142. Electrical power can also be delivered to structure 142 inductively as shown. described below with reference to Figures 14-16.

As the electrical current is applied to the shape memory material 146, it is heated by resistivity causing a phase change and a corresponding shape change. As the electrical current is applied to the bimetallic material 148, it is heated by resistivity causing a differential in thermal expansion and a corresponding change in shape. In either case, the 146-148 material is designed in such a way that the change in f The form causes expansion of structure 142 to mechanically activate barorecepores 30 by stretching or otherwise deforming them and / or vascular wall 40. Upon removal of electrical current, material 146/148 cools and structure 142 returns to its geometry relaxed in such a way that the baroreceptors 30 and / or the vascular wall 40 return to their nominal state. Thus, by selectively expanding structure 142, baroreceptors 30 adjacent to it can be selectively activated.

Reference is now made to Figures 7A and 7B which show schematic illustrations of a baroreceptor activation device 160 in the form of an extravascular deformable structure. The extravascular deformable structure device 160 is substantially the same as the intravascular deformable structure device 140 described with reference in Figures 6A and 6B, except that the extravascular device 160 is available. This is around the vascular wall, and therefore compresses rather than expands, the vascular wall 40. The deformable structure device 160 includes a wire, braid, or other graft-like structure 162 that comprises one or more individual structural members connected to an electrical cable 164. Each of the structural members may comprise a shape memory material 166 ( eg nickel titanium alloy) as illustrated in Figure 7C or a bimetallic material 168 as illustrated in Figure 7D. Structure 162 can be unipolar as shown using surrounding tissue as ground, or bipolar or multipolar using wires connected to each end of structure 162. Electrical power can also be delivered to structure 162 inductively as described below with reference. to Figures 14-16.

When the electrical current is applied to the shape memory material 166 it is heated by resistivity c causing a phase change and a corresponding change in its shape. As the electrical current is applied to the bimetallic material 168, it is heated by resistivity causing a differential in thermal expansion and a corresponding change in its shape. In either case, the 166/168 material is designed in such a way that the change in its shape causes constriction of the structure 162 to mechanically activate the baroreceptors 30 by compressing or otherwise deforming the baroreceptors 30 and / or the wall. vascular 40. By removing the electrical current, the material 166/168 cools and the structure 162 returns to its relaxed geometry such that the baroreceptors 30 and / or the vascular wall 40 return to their nominal state. Thus, by selectively compressing structure 162, baroreceptors 30 adjacent to it can be selectively activated.

Reference is now made to Figures 8A and 8B which show schematic illustrations. attics of a baroreceptor activation device 180 in the form of an extravascular flow regulator that artificially creates a back pressure adjacent to the baroreceptors 30. The flow regulating device 180 includes an external compression device 182, which may comprise any of the external compression devices described with reference to Figures 5A and 5B. External compression device 182 is operatively connected to driver 66 of control system 60 via cable 184, which may comprise a fluid line or electrical cable, depending on the type of external compression device 182 used. The external compression device 182 is disposed around the distal vascular wall of the baroreceptors 30. For example, the external compression device 182 may be located at the distal points of the external or internal carotid arteries 18/19 to create a back pressure adjacent to it. s baroreceptors 30 in the carotid sinus region 20. Alternatively, the external compression device 182 may be located in the right subclavian artery 13, the right common carotid artery 14, the left common carotid artery 15, the left subclavian artery 16, the brachiocephalic artery 22 to create back pressure adjacent to the baroreceptors 30 in the aortic arch 12.

As the external compression device 182 actuates, the vascular wall is constricted thereby reducing the size of the vascular lumen therein. By reducing the size of the vascular lumen, the proximal pressure of the external compression device 182 is increased thereby by expanding the vascular wall. Thus, by selectively activating the external compression device 182 to constrict the vascular lumen and create back pressure, the baroreceptors 30 can be selectively activated.

Reference is now made to Figures 9A and 9B which show illus Schematic drawings of a baroreceptor activation device 200 in the form of a regular intravascular flow which artificially creates a back pressure adjacent to the baroreceptors 30. The intravascular flow regulator device 200 is substantially similar in function and use as the extravascular flow regulator 180 described with reference to Figures 8A and 8B, except that the intravascular flow regulator device 200 is disposed in the vascular lumen.

The intravascular flow regulator 200 includes an internal valve 202 for at least partially closing the distal vascular lumen of the baroreceptors 30. By at least partially closing the distal vascular lumen of the baroreceptors 30, a proximal back pressure of the internal valve 202 is created in such a manner. such that the vascular wall expands to activate baroreceptors 30. The internal valve 202 can be positioned in any of the locations described with reference above the external compression device 182, except that the internal valve 202 is positioned

ES 2 330 833 T3 within the vascular lumen. Specifically, the internal compression device 202 may be located in distal portions of the external or internal carotid arteries 18/19 to create back pressure adjacent to the baroreceptors 30 in the region of the carotid sinus 20. Alternatively, the internal compression device 202 may be located in the right subclavian artery 13, the right common carotid artery 14, the left common carotid artery 15, the left subclavian artery 16, or the brachiocephalic artery 22 to create back pressure adjacent to the baroreceptors. 30 in the aortic arch 12.

Internal valve 202 is operably coupled to driver 66 of control system 60 via electrical cable 204. Control system 60 can be selectively open, closed, or change the flow resistance of the valve. vula 202 as described in more detail hereinafter. Internal valve 202 may include valve leaflets 202 (bi-leaf or tri-leaf) which rotate within housing 208 about an axis between an open position and a closed position. The closed position can be fully closed or partially closed, depending on the desired amount of back pressure to be created. The internal opening and closing valve 202 can be selectively controlled by altering the resistance to the rotation of the leaflets 206 or by altering the opening force of the leaflets 206. The rotational resistance of the leaflets 206 can be altered using carried electromagnetically actuated metal bearings. by the housing 208. The opening force of the flakes 206 can be altered by using electromagnetic wires in each of the flakes to selectively magnetize the flakes such that they either repel or attract each other. another, thus facilitating the opening and closing of the valve, respectively.

A wide variety of intravascular flow regulators can be used in place of the internal valve 202. For example, internal inflatable balloon devices such as described in US Patent No. 4,682,583 to Burton et al and US Patent No. US No. 5,634,874 to Grundei et al, may be adapted for use in place of valve 202. Such inflatable balloon devices can be operated in a similar manner as the inflatable yoke 122 described with reference to Figure 5. Specifically, in this embodiment, the impeller 66 would comprise a pressure / vacuum source (ie, an inflation device). which selectively inflates and deflates the inner balloon. Upon inflation, the balloon expands to partially occlude blood flow and create back pressure to mechanically activate the baroreceptors 30 by stretching or deforming them accordingly. somehow and / or vascular wall 40. Upon deflation, the inner balloon returns to its normal profile so that flow is not impeded and back pressure is removed. Thus, by selectively inflating the inner balloon, the proximal baroreceptors 30 can be selectively activated creating back pressure.

Reference is now made to Figures 10A and 10B which show schematic illustrations of a baroreceptor activation device 220 in the form of magnetic particles 222 disposed in vascular wall 40. Magnetic particles 222 may comprise magnetically responsive materials (that is, , iron-based materials) and can be magnetically neutral or magnetically active. Preferably, the magnetic particles 222 comprise permanent magnets having an elongated cylinder shape with north and south poles to respond strongly to magnetic fields. The magnetic particles 222 are actuated by a wire electromagnetic 224 which is operably coupled to driver 66 of control system 60 via electrical cable 226. Electromagnetic wire 224 may be implanted as shown, or located outside the body, in which case the driver 66 and the rest of the control system 60 would also be located outside the body. By selectively activating the electromagnetic wire 224 to create a magnetic field, the magnetic particles 222 can be repelled, attracted, or rotated. Alternatively, the magnetic field created by electromagnetic wire 224 can be alternated such that magnetic particles 222 vibrate within vascular wall 40. When magnetic particles are repelled, attracted, they are caused to rotate, vibrate, or move in some other way. By the magnetic field created by the electromagnetic wire 224, the baroreceptors 30 are mechanically activated.

The electromagnetic wire 224 is preferably placed nte as close as possible to magnetic particles 222 in vascular wall 40, and can be placed intravascularly, extravascularly, or at any of the alternative locations discussed with reference to the inducer shown in Figures 14-16. Magnetic particles 222 can be implanted into vascular wall 40 by injecting a ferro-fluid or suspension of ferroparticles into the vascular wall adjacent to baroreceptors 30. To increase biocompatibility, particles 222 can be coated with a polymeric ceramic or other material. inert material. The injection of the fluid carrying the magnetic particles 222 is preferably carried out percutaneously.

Reference is now made to Figures 11A and 11B which show schematic illustrations of a baroreceptor activation device 240 in the form of one or more transducers 242. Preferably, the transducers 242 comprise an arrangement. tion that surrounds the vascular wall. Transducers 242 can be positioned intra or extravascularly adjacent to baroreceptors 30. In this embodiment, the transducers 242 comprise devices that convert the electrical signals into some physical phenomenon, such as mechanical vibration or acoustic waves. Electrical signals are provided to transducers 242 via electrical cables 244 which are connected to driver 66 of control system 60. By selectively activating transducers 242 to create a physical phenomenon, baroreceptors 30 can be mechanically activated.

Transducers 242 may comprise an acoustic transmitter which transmits sonic or ultrasonic sound waves to vascular wall 40 to activate baroreceptors 30. Alternatively, transducers 242 may comprise a piezoelectric material which vibrates the vessel wall to activate baroreceptors 30 . What

IT IS 2 330 833 T3 A further alternative, transducers 242 may comprise an artificial muscle that flexes by application of an electrical signal. An example of an artificial muscle transducer comprises a plastic impregnated with a lithium perchlorate electrolyte disposed between sheets of polypyrrole, a conductive polymer. Such plastic muscles can be electrically activated to cause deflection in different directions depending on the polarity of the applied current.

Reference is made to Figures 12A and 12B which show schematic illustrations of a baroreceptor activation device 260 in the form of a local fluid delivery device 262 suitable for delivering a fluid chemical or biological agent to the adjacent vascular wall. baroreceptors 30. Local fluid delivery device 262 can be located intravascularly, extravascularly, or intramurally. Pa For purposes of illustration only, the local fluid delivery device 262 is positioned extravascularly.

Local fluid delivery device 262 may include proximal and distal seals 262 that retain fluid agent disposed in lumen or cavity 268 adjacent to vascular wall. Preferably, local fluid delivery device 262 completely surrounds vascular wall 40 to maintain an effective seal. Those skilled in the art will recognize that local fluid delivery device 262 can comprise a wide variety of implantable drug delivery devices or pumps known in the art.

The local fluid delivery device 260 is connected to a fluid line 264 that is connected to the impeller 66 of the control system 60. In this embodiment, the impeller 66 comprises a pressure / vacuum source and a fluid reservoir containing the age nte desired biological chemical fluid. The chemical or biological fluid agent can comprise a wide variety of stimulant substances. Examples include veratridin, bradykinin, prostaglandins, and related substances. Such stimulatory substances activate baroreceptors 30 directly or increase their sensitivity to other stimuli and therefore can be used in combination with the other baroreceptor activation devices described herein. Other examples include growth factors and other agents that modify the function of the baroreceptors 30 or the cells of the vascular tissue surrounding the baroreceptors 30 causing the baroreceptors 30 to activate or causing the alteration of their responsiveness or pattern of activation to others. stimuli. Injectable stimulators that are remotely introduced, as described in U.S. Patent No. 6,061,596 which is incorporated herein as re ferences can be used with the present invention.

Alternatively, fluid delivery device 260 can be used to deliver a photochemical that is essentially inert until activated by light to have a stimulatory effect as described above. In this embodiment, fluid delivery device 260 would include a light source such as a light-emitting iodine (LED), and driver 66 of control system 60 would include a pulse generator for the LED combined with a pressure source. / vacuum and a previously described fluid reservoir. The photochemical would be delivered with fluid delivery device 260 as described above, and the photochemical would be activated, deactivated, or modulated by activating, deactivating, or modulating the LED.

As a further alternative, the fluid delivery device 260 can be used to deliver a fluid warm or hot (eg, saline) to thermally activate the baroreceptors 30. In this embodiment, the impeller 66 of the control system 60 would include a heat generator to heat the fluid, combined with a pressure / vacuum source and a reservoir. of fluid previously described. Hot or warm fluid would be delivered and preferably circulated with fluid delivery device 260 as described above, and the temperature of the fluid would be controlled by pusher 66.

Reference is now made to Figures 13A and 13B which show schematic illustrations of a baroreceptor activation device 280 in the form of an intravascular electrically conductive structure or electrode 282. The electrode structure 282 may comprise a self-expanding or expandable wire with balloon, tissue, or other graft-like structure disposed in the vascular lumen. The structure of electro do 282 can serve the dual purpose of maintaining the lumen throughput level while also releasing electrical stimuli. To this end, the electrode structure 282 can be implanted using a conventional intravascular graft and filter delivery techniques. Preferably, the electrode structure 282 comprises a geometry that allows blood to be perfused therethrough. The electrode structure 282 comprises an electrically conductive material that can be selectively insulated to contact the interior surface of vascular wall 40 at desired locations, and limit external electrical contact with blood flowing through the vessel and other tissues.

Electrode structure 282 is connected to electrical cable 284 which is connected to driver 66 of control system 60. Driver 66, in this embodiment, may comprise a power amplifier, pulse generator, or the like. To selectively deliver electrical control signals to structure 282. As previously mentioned, the electrical control signal generated by driver 66 can be continuous, periodic, episodes, or a combination of the foregoing, as dictated by an algorithm contained in memory 62 of control system 60. The control signals Continuous include a constant pulse, a constant pulse train, a triggered pulse, and a triggered train of pulses. The periodic control signals include each of the continuous control signals described above having a designated start time and a designated duration. The per-episode control signals include each of the above-described continuous control signals which are triggered by one episode.

ES 2 330 833 T3

By selectively activating, deactivating, or otherwise modulating the electrical control signal transmitted by the electr structure For 282, electrical energy can be delivered to the vascular wall to activate baroreceptors 30. As previously discussed, activation of baroreceptors 30 can occur directly or indirectly. In particular, the electrical signal supplied to vascular wall 40 by electrode structure 282 can cause the vascular wall to stretch or deform in some other way thereby indirectly activating the baroreceptors 30 disposed there. Alternatively, electrical signals delivered to the vascular wall by electrode structure 282 can directly activate baroreceptors 30 by changing the electrical potential across baroreceptors 30. In either case, the electrical signal is supplied to vascular wall 40 immediately adjacent to baroreceptors 30. It is also contemplated that electrode structure 282 can supply thermal energy using a semiconductor material that has a high resistance. a such that the electrode structure 282 resistively generates heat as electrical energy is applied.

Various alternative embodiments are contemplated for electrode structure 282, including its design, implanted location, and method of electrical activation. For example, electrode structure 282 can be unipolar as shown in Figures 13A and 13B using the surrounding tissue as ground, or bipolar using wires connected to each end of structure 282 as shown in Figures 18A and 18B. In Figures 18A and 18B, electrode structure 282 includes two or more individual electrically conductive members 283/285 that are electrically isolated at their respective cross points using insulating materials. Each of the members 283/285 is connected to a separate conductor contained within the electrical cable 284. Alternatively, a bipole arrangement may be used as described. e in more detail with reference to Figure 21. As a further alternative, a multipolar arrangement may be used when three or more electrically conductive members are included in structure 282. For example, a tripolar arrangement may be provided for an electrically conductive member having a polarity arranged between two electrically conductive members having the opposite polarity.

In terms of electrical drive, electrical signals can be supplied directly to electrode structure 282 as described with reference to Figures 13A and 13B, or supplied indirectly using an inductor as illustrated in Figures 14-16 and 21. Embodiments of Figures 14-16 and 21 utilize an inductor 286 that is operatively connected to driver 66 of control system 60 via electrical cable 284. Inductor 286 comprises an electrical winding that creates a magnetic field 287 (as described see Figure 21) around electrode structure 282. Magnetic field 287 can be alternated by alternating the direction of current flow through inductor 286. Accordingly, inductor 286 can be used to create a current flow in electrode structure 282 to thereby supply electrical signals to vascular wall 40 to directly or indirectly activate baroreceptors 30. Inductor 286 can be covered. with an electrically insulating material to eliminate direct electrical stimulation of the tissues surrounding inducer 286. An inductively coupled electrode structure 282 is described in more detail with reference to Figures 21A-21C.

The embodiments of Figures 13-16 can be modified to form a cathode / anode arrangement. Specifically, the electrical inductor 286 would be connected to the driver 66 as shown in Figures 14-16 and the electrode structure 282 it would be connected to driver 66 as shown in Figure 13. With this arrangement, electrode structure 282 and inductor 286 can be any suitable geometry and do not need to be wired for induction purposes. Electrode structure 282 and inductor 286 would comprise a cathode / anode or anode / cathode pair. For example, when activated, cathode 282 can generate a primary stream of electrons that travels through the interelectrode space (vascular tissue and baroreceptors 30) toward anode 286. The cathode is preferably cold, as opposed to thermionic, during electron emission. Electrons can be used to electrically or thermally activate the baroreceptors 30 as previously discussed.

The electrical inductor 286 is preferably disposed as close as possible to the structure of the electrode 282. For example, the inductor 286 may be disposed adjacent to the vascular wall as illustrated in Figures 14A and 14B. Alternatively, inducer 286 may be disposed in an adjacent vessel as illustrated in Figures 15A and 15B. If electrode structure 282 is disposed in carotid sinus 20, for example, inducer 286 may be disposed in internal jugular vein 21 as illustrated in Figures 15A and 15B. In the embodiment of Figures 15A and 15B, the electrical inductor 286 may comprise a structure similar to the electrode structure 282. As a further alternative, the electrical inductor 286 may be disposed outside the patient's body but as close as possible to the electrode structure 282. If the electrode structure 282 is disposed in the carotid sinus 20, for example, the electrical inductor 286 may be disposed on the right or left side of the patient's neck as illustrated in Figures 16A and 16B. In the embodiment of Figures 16A and 16B, where the electrical inductor 286 is disposed outside the body of For the patient, the control system 60 may also be disposed outside the patient's body.

In terms of implant location, electrode structure 282 may be arranged intravascularly as described with reference to Figures 13A and 13B, or arranged extravascularly as described with reference to Figures 17A and 17B, which show schematic illustrations of a baroreceptor activation device 300 in the form of an electrically conductive extravascular electrode or structure 302. Except as described herein, the extravascular electrode structure 302 is the same in design, function, and use as the intravascular electrode structure 282. The electrode structure 302 may comprise a wire, braid, or other structure capable of surrounding the vascular wall. Alternatively, the electrode structure 302 may comprise one or more

ES 2 330 833 T3 electrode patches distributed around the external surface of the vascular wall. Since the electrode structure 302 is disposed on the outer surface of the vascular wall, intravascular delivery techniques may not be practical, but minimally invasive surgical techniques will suffice. The extravascular electrode structure 302 can receive electrical signals directly from the driver 66 of the control system 60 via electrical cable 304, or indirectly using an inductor (not shown) as described with reference to Figures 14-16.

Reference is now made to Figures 19A and 19B which show schematic illustrations of a baroreceptor activation device 320 in the form of electrically conductive particles 322 disposed in the vascular wall. This is substantially the same as the arrangements described with reference to Figures 13-18, except that the electrically conductive particles 322 are arranged within the vascular wall, as opposed to electrically conductive structures 282/302 that are disposed on either side of the vascular wall. Furthermore, this arrangement is similar to the arrangement described with reference to Figure 10, except that the electrically conductive particles 322 are not necessarily magnetic as is the case with magnetic particles 222, and the electrically conductive particles 322 are driven by an electromagnetic field at instead of a magnetic field.

In this embodiment, the driver 66 of the control system 60 comprises an electromagnetic transmitter such as a radio frequency or microwave transmitter. Electromagnetic radiation is created by transmitter 66 which is operatively coupled to antenna 324 via electrical wire 326. Electromagnetic waves are emitted by antenna 324 and received by electrically conductive particles 322 disposed on the vascular wall. r 40. The electromagnetic energy creates an oscillating current flow within the electrically conductive particles 322 and depending on the intensity of the electromagnetic radiation and the resistivity of the conductive particles 322, it can cause the electrical particles 322 to generate heat. The electrical or thermal energy generated by electrically conductive particles 322 can directly activate baroreceptors 30, or indirectly activate baroreceptors 30 via surrounding vascular wall tissue.

Electromagnetic radiation transmitter 66 and antenna 324 may be disposed on the patient's body, with antenna 324 disposed adjacent to conductive particles in vascular wall 40 as illustrated in Figures 19A and 19B. Alternatively, antenna 324 may be arranged in any of the positions described with reference to the electrical inductor shown in Figures 14-16. It is also contemplated that the electromagnetic radiation transmitter 66 and antenna 324 can be used in combination with the electrically conductive intravascular and extravascular structures 282/302 described with reference to Figures 13-18 to generate thermal energy on either side of the vascular wall.

Alternatively, the electromagnetic radiation transmitter 66 and antenna 324 can be used without the electrically conductive particles 322. Specifically, electromagnetic radiation transmitter 66 and antenna 324 can be used to deliver electromagnetic radiation (eg, RF, microwaves) directly to baroreceptors 30 or tissue adjacent thereto to cause localized heating, thereby thermally inducing a signal from baroreceptors 30.

Reference is now made to Figures 20A and 20B which show schematic illustrations of a baroreceptor activation device 340. in the form of a Peltier effect device 342. The Peltier effect device 342 can be positioned extravascularly as illustrated, or it can be positioned intravascularly similar to an intravascular graft or filter. Peltier effect device 342 is operatively connected to driver 66 of control system 60 via electrical cable 344. Peltier effect device 342 includes two dissimilar metals or semiconductors 343/345 separated by a heat transfer junction 347. In this particular embodiment, driver 66 comprises a power source that supplies electrical energy to dissimilar metals or semiconductors 343/345 to create current flow through thermal junction 347.

When current is supplied in an appropriate direction, a cooling effect is created at the thermal junction 347. There is also a heating effect created at the thermal junction between the individual wires 344 connecting cted to dissimilar metals or semiconductors 343/345. This heating effect, which is proportional to the cooling effect, can be used to activate baroreceptors 30 by positioning the junction between electrical leads 344 and dissimilar metals or semiconductors 343/345 adjacent to vascular wall 40.

Reference is now made to Figures 21A-21C which show schematic illustrations of a preferred embodiment of an inductively activated electrode structure 282 for use with the embodiments described with reference to Figures 14-16. In this embodiment, current flow in electrode structure 282 is induced by a magnetic field 287 created by inductor 286 that is operatively coupled to driver 66 of control system 60 via electrical wire 284. Electrode structure 282 preferably comprises a self-expanding multi-strand braid structure including a plurality of individual members 282a, 282b, 282c and 282d. However, the electrode frame structure 282 may simply comprise a single wire.

Each of the individual wire members 282a-282d comprising the electrode structure 282 consists of a plurality of individual wire turns 281 connected end-to-end as illustrated in Figures 21B and 21C. Figure 21C is a detailed view of the connection between adjacent turns of wire 281 as shown in Figure 21B. Each turn of wire 281 comprises electrically insulated or receiving wires

ES 2 330 833 T3 in which a flow current is established when a changing magnetic field 287 is created by inductor 286. Inductor 286 is preferably covered with an electrically insulating material to eliminate direct electrical stimulation of the surrounding tissues. inductor 286. The current flow through each turn d The wire 281 results in a potential drop 288 between each end of the turn of wire 281. With a defined potential drop at each junction between adjacent turns of wire 281, a current flow cell is created in the vessel wall adjacent to each junction. Thus an arrangement or plurality of bipoles is created by the electrode structure 282 and distributed evenly around the vascular wall. Each turn of wire 281 comprises an electrically conductive wire material 290 surrounded by an electrically insulating material 292. The end of each turn of wire 281 is connected by electrically insulated material 294 such that each turn of wire 281 remains electrically insulated. Insulating material 294 mechanically bonds but electrically insulates turns of wire 281 so that each turn 281 responds with a similar potential drop 288 when current flow is induced by the magnetic field cam biant 287 of inductor 286. An exposed portion 296 is provided at the end of each turn of wire 281 to facilitate contact with the tissue of the vascular wall. Each portion 296 comprises an insulated electrode in contact with the vascular wall. The changing magnetic field 287 of inductor 286 generates a potential drop in each turn of wire 281 thereby creating small cells of current flow in the vascular wall corresponding to adjacent exposed regions 296. The creation of multiple current cells along the inner wall of the blood vessel serves to create a cylindrical region of relatively high current density such that the baroreceptors 30 are activated. However, the cylindrical current density field rapidly reduces to a negligible current density near the outer wall of the vessel wall, which serves to limit the leakage of foreign currents to minimize or eliminate an ac unwanted activation of extravascular tissues and structures such as nerves or muscles.

Reference is now made to Figures 22A-22F which show schematic illustrations of various possible electrode arrangements around the carotid sinus 20 for extravascular electrical activation embodiments, such as the baroreceptor activation device 300 described with reference to Figures 17A and 17B. The electrode designs illustrated and described hereinafter may be particularly suitable for connection to the carotid arteries in or near the carotid sinus, and may be designed to minimize stimulation of foreign tissues.

In Figures 22A - 22F, the carotid arteries are shown, including the common 14, external, and internal 19 carotid arteries. The location of the carotid sinus 20 can be identified by a bulge marked 21, which is typically located in the internal carotid artery. rna 19 just distal to the bifurcation, or extending through the bifurcation from the common carotid artery 14 to the internal carotid artery 19.

The carotid sinus 20, and in particular the carotid sinus bulge 21, may contain a relatively high density of baroreceptors 30 (not shown) in the vascular wall. For this reason, it may be desirable to position the electrodes 302 of the trigger device 300 on and / or around the breast bulge 21 to maximize the response of the baroreceptors and to minimize the stimulation of foreign tissues.

It should be understood that device 300 and electrodes 302 are purely schematic, and only a portion of which may be shown, for purposes of illustrating various positions of electrodes 302 on and / or around the carotid sinus 20 and the pons. twenty-one. In each of the embodiments described herein, the electrodes 302 may be monop olar (the electrodes are cathodes, the surrounding tissue is the anode or earth), bipolar (cathode-anode pairs), or tripolar (anode-cathode-anode sets). Specific extravascular electrode designs are described in more detail below.

In Figure 22A, the electrodes 302 of the extravascular electrical actuator 300 extend around a portion of the entire circumference of the sinus 20 in a circular fashion. In Figure 22B, the electrodes 302 of the extravascular electrical actuator 300 extend around a portion or the entire circumference of the sinus 20 in a helical fashion. In the helical arrangement shown in Figure 22B, the electrodes 302 can be wrapped around the sinus 20 any number of times to establish the desired contact and covering of the electrode 302. In the circular arrangement shown in Figure 22A, a single pair of electrodes 302 can be wrapped around sinus 20, or a The plurality of pairs of electrodes 302 can be wrapped around the sinus 20 as shown in Figure 22C to establish greater contact and coverage of the electrode 302.

The plurality of pairs of electrodes 302 may extend from a proximal point of sinus 20 or bulge 21 to a distal point of sinus 20 or bulge 21 to ensure activation of baroreceptors 30 through sinus region 20. Electrodes 302 they can be connected to a single channel or to multiple channels as will be discussed in more detail later. The plurality of pairs of electrodes 302 can be selectively activated for purposes of targeting a specific area of ​​the sinus 20 to increase the response of the baroreceptors, or for purposes of reducing the exposure of areas of tissue to activation to maintain the response of the baroreceptors over a long term.

In Figure 22D, the electrodes 302 extend around the cir full breast circumference 20 in a crisscross shape. The criss-cross arrangement of electrodes 302 makes contact with the internal and external carotid arteries 18 around the carotid sinus 20. Similarly, in Figure 22E, the electrodes 302 extend around all or a portion of the circumference of the sinus 20, including the internal 19 and external 18 carotid arteries at the bifurcation, and in some cases the common carotid artery 14 In Figure 22F, the electrodes 302 extend

ES 2 330 833 T3 around all or a portion of the circumference of sinus 20, including the internal 19 and external 18 distal carotid arteries of the bifurcation. In Figures 22E and 22F, the extravascular electrical actuation devices 300 are shown including a substrate or base structure 306 that can encapsulate and isolate the electrodes 302 and can provide means for connecting the sinus 20 as described in more detail below. . <

From the above discussion with reference to Figures 22A-22F, it will be apparent that there are a number of suitable arrangements for the electrodes 302 of the trigger device 300, with respect to the carotid sinus 20 and associated anatomy. In each of the examples given above, the electrodes 302 are wrapped around a portion of the carotid structure, which may require a deformation of the electrodes 2 from their relaxed (eg, straight) geometry. To reduce or eliminate such deformations, the electrodes 302 and / or the base structure 306 can have a relaxed geometry that substantially conforms to the shape of the carotid anatomy at the point of attachment. In other words, the electrodes 302 and base structure 310 can be preconfigured to conform to the carotid anatomy in a substantially relaxed state. Alternatively, the electrodes 302 may have a geometry and / or orientation that reduces to the amount of voltage at the electrode 302.

For example, in Figure 23, the electrodes 302 are shown in a serpentine or wavy shape. The serpentine shape of the electrodes 302 reduces the amount of stress suffered by the electrode material when it is wrapped around a carotid structure. Furthermore, the serpentine shape of the electrodes increases the surface area of ​​contact of the electrode 302 with the carotid tissue. Alternatively, the electrodes 302 may be arranged to be substantially orthogonal to the direction of the sheath (that is, substantially parallel to the axis of the carotid arteries) as shown in Figure 24. In this alternative, the electrodes 302 each have a length and a width or diameter, where the length is substantially greater than the width or diameter. Electrodes 302 each have an axis parallel longitudinal to the length thereof, where the longitudinal axis is orthogonal. to the direction of the sheath and substantially parallel to the longitudinal axis of the carotid artery around which the device 300 is wrapped. As with the multiple electrode embodiments previously described, the electrodes 302 can be connected to a single channel or to channels multiple as discussed in more detail below.

Reference is again made to Figures 25-28 which schematically illustrate various multiple channel electrodes for the extravascular electrical actuator 300. Figure 25 illustrates a six (6) electrode arrangement including six (6) spaced apart elongated electrodes 302 that extend adjacent and parallel to one another. Electrodes 302 are each connected to multichannel cable 304. Some of the electrodes 302 may be common, thereby reducing the number of channels required in the cable 304.

Base structure or substrate 306 may comprise a matte Flexible and electrically insulating material suitable for implantation, such as silicone, perhaps reinforced with a flexible material such as polyester textile. Base 306 may be of a length suitable to wrap around all (360 °) or a portion (ie, less than 360 °) of the circumference of one or more of the carotid arteries adjacent to the carotid sinus 20. Electrodes 302 may extend around a portion (that is, less than 360 ° such as 270 °, 180 °, or 90 °) of the circumference of one or more of the carotid arteries adjacent to the carotid sinus 20. To this end, the Electrodes 302 may have a length that is less than (eg, 75%, 50%, or 25%) than the length of the base 206. Electrodes 302 can be parallel, orthogonal, or oblique to the length of base 306, which is generally orthogonal to the axis of the carotid artery around which it is arranged.

Electrodes 302 may comprise rounded wire, rectangular tape lar or sheet formed of an electrically conductive and radiopaque material such as platinum. Base structure 306 substantially encapsulates electrodes 302, leaving only an exposed area for electrical connection to extravascular carotid sinus tissue. For example, each electrode 302 may have a partially recessed base 206 and may have an exposed side along all or a portion of its length for electrical connection to carotid tissue. Electrical pathways through carotid tissues can be defined by one or more pairs of elongated electrodes 302.

In all of the embodiments described with reference to Figures 25-28, the multichannel electrodes 302 can be selectively activated for mapping purposes and to target a specific area of ​​the carotid sinus 20 to determine the best combination of electrodes 302 (e.g., individual pairs, or groups of pairs) to activate the maximum response of the ba roreceptors, as described here in various places. In addition, multiple channel electrodes 302 can be selectively activated for purposes of reducing the exposure of tissue areas to activation to maintain long-term efficacy as described, as described in various parts herein. For these purposes, it may be useful to use more than two (2) electrode channels. Alternatively, the electrodes 302 can be connected to a single channel whereby the baroreceptors are activated uniformly across the sinus region 20.

An alternative multiple channel electrode design is illustrated in Figure 26. In this embodiment, device 300 includes sixteen (16) individual electrode pads 302 connected to a 16 channel cable 304 via 4 channel connectors 303. In this embodiment, the circular pads of the electrode 302 are partially encapsulated by the base structure 306 to leave one face of each button electrode 302 exposed for electrical connection to carotid tissues. With this arrangement, the electrical pathways through the carotid tissues can be defined by one or more pairs (bipolar) or groups (tripolar) of electrode pads 302.

ES 2 330 833 T3

A variation of the multiple channel pad electrode design is illustrated in Figure 27. In this embodiment, device 300 includes sixteen (16) individual circular pad electrodes 302 surrounded by sixteen (16) rings 305, which collectively may be referred to as 302/305 concentric electrode pads. Pad electrodes 302 are connected to 17 channel cable 304 through 4 channel connectors 303 and rings 305 are commonly connected to 17 channel cable 304 through single channel connector 307. In this embodiment, the circular-shaped electrodes 302 and the rings 305 they are partially encapsulated by base structure 306 to leave one face of each electrode pad 302 and one face of each ring 305 exposed for electrical connection to the carotid tissues. Alternatively, two rings 305 may surround each electrode 302, the rings 305 being commonly connected. With these arrangements, electrical pathways through the carotid tissues can be defined between one or more pairs of electrode pads 302 / rings 305 as assemblies to create localized electrical pathways.

Another variation of the multi-channel pad electrode design is illustrated in Figure 28. In this embodiment, device 300 includes an IC control chip 310 connected with a 3-channel cable 304. Control chip 300 is also connected to sixteen (16) individual pad electrodes 302 via 4-channel connectors 303. The control chip 310 allows the number of channels in the cable 304 is reduced using a coding system. Control system 60 sends a coded control signal that is received by chip 310. Chip 310 converts the code and enables or disables selected electrode pairs 302 in accordance with the code.

For example, the control signal may comprise a pulse waveform, where each pulse indicates a different code. The code for each pulse causes chip 310 to enable one or more pairs of electrodes, and disable the remaining electrodes. Thus, the pulse is transmitted only to the enabled electrode pair corresponding to the code sent with that pulse. Each subsequent pulse will have a different code than the preceding pulse such that chip 310 enables and disables a different set of electrodes 302 corresponding to the different code. Thus, virtually any number of electrode pairs can be selectively activated using control chip 310, without the need for d There is a separate channel in cable 304 for each electrode 302. By reducing the number of channels in cable 304, the size and cost of the cable can be reduced.

Optionally, the IC chip 310 can be connected to a feedback sensor 80, taking advantage of the same functions as described with reference to Figure 3. In addition, one or more of the electrodes 302 can be used as feedback sensors when they are not present. enabled for activation. For example, such a feedback sensing electrode can be used to measure and monitor electrical conduction in the vascular wall to provide data analogous to an ECG. Alternatively, such a feedback sensing electrode can be used to sense a change in impedance due to changes in blood volume during a pulse pressure to provide data indicative of heart rate, blood pressure, or other physiological parameter.

Reference is now made to Figure 29 which schematically illustrates an extravascular electrical activation device 300 that includes a support collar or anchor 312. In this embodiment, the activation device 300 is wrapped around the internal carotid artery 19 and the carotid sinus 20, and the support collar 312 is wrapped around the common carotid artery 14. Trigger 300 is connected to support collar 312 by wires 304, which act as a loose tether. With this arrangement, the collar 312 isolates the activation device from the movements and forces transmitted by the cables 304 proximal to the support collar, such as those that can be encountered by movements of the control system 60 and / or driver 66. As an alternative to support collar 312, a strain relief (not shown) may be connected to base frame 306 of trigger device 300 at the junction between wires 304 and base 306. In either embodiment, position d device 300 with respect to carotid anatomy may be better maintained despite movements of other parts of the system.

In this embodiment, the base structure 306 of the trigger device 300 may comprise a molded tube, a tubular extrusion, or a sheet of material wrapped in the form of a tube using a suture flap 308 with sutures 309 as shown. Base structure 306 can be formed from a flexible, biocompatible material such as silicone, which can be reinforced with a flexible material such as a polyester textile available under the trade name DA-CRON to form a composite structure. The internal diameter of the base frame 306 may correspond to the external diameter of the carotid artery at the implantation site eg 6-8mm. The wall thickness of the base structure 306 can be very thin to maintain flexibility and a low profile, for example less 1 mm. If device 300 is to be disposed around a breast protrusion 21, it may be correspondingly formed as a protrusion on the base structure to give additional support and assistance in positioning.

Electrodes 302 (shown in phantom lines) can comprise round wire, rectangular tape, or sheets, formed from an electrically conductive, radiopaque material such as platinum or platinum-iridium. The electrodes can be molded into the base frame 306 or adhesively connected to the internal diameter thereof, leaving a portion of the electrode arranged for electrical connection to the carotid tissues. Electrodes 302 can span less than the total internal circumference (eg, 300 °) of base frame 306 to avoid shortening. Electrodes 302 can have any of the shapes and arrangements previously described. For example, as shown in Figure 29, you can use two rectangular ribbon electrodes 302, each having a width of 1 mm spaced 1.5 mm from each other.

ES 2 330 833 T3

The support collar 312 can be formed similarly to the base structure 306. For example, the support collar can comprise molded tube, a tubular extrusion, or a sheet of material wrapped in the form of a tube using a suture flap 315 with sutures 313 as shown. Support collar 312 can be formed from a flexible, biocompatible material such as silicone, which can be reinforced to form a composite structure. The cables 304 are secured to the support collar 312, leaving a space in the cables 304 between the support collar 312 and the activation device 300.

In all of the extravascular embodiments described herein including electrical activation, it may be desirable to secure the activation device to the vascular wall using sutures or other means. fixation os. For example, sutures 311 can be used to maintain the position of the electrical actuator 300 relative to the carotid anatomy (or other vascular site containing baroreceptors). Such sutures 311 can be connected to base structure 306, and pass through all or a portion of the vascular wall. For example, sutures 311 can be braided around base structure 306, through the adventitia of the vascular wall, and tied. If the base frame 306 comprises a patch or otherwise partially surrounds the carotid anatomy, the corners and / or ends of the base frame can be sutured, with additional sutures evenly distributed therebetween. In order to minimize the propagation of a hole or tear through the base structure 306, a reinforcing material such as a polyester fabric can be embedded in the silicone material. In addition to sutures, other fixing means such as staples or a biocompatible adhesive for example.

Reference is now made to Figure 30 which schematically illustrates an alternative extravascular electrical trigger device 300 that includes one or more electrode edges 316 interconnected by spine 317. Optionally, a support collar 312 having one or more ( no electrodes) ridges 316 in order to isolate the activation device 300 from movements and forces transmitted by the proximal cables 304 of the support collar 312.

The ridges 316 of the activation device 300 are sized to conform to the carotid anatomy, such as the internal carotid artery 19 adjacent to the carotid sinus 20. Similarly, the ridges 316 of the support collar 312 can be sized such that they fit around the carotid anatomy, such as the common carotid artery 14 proximal to the carotid sinus 20. Edges 316 can be separated placed over a carotid artery and closed around it to secure device 300 to the carotid anatomy.

Each of the edges 316 of the device 300 includes an electrode 302 on the internal surface thereof for electrical connection to the carotid tissue. The ridges 316 provide insulating material around the electrodes 302, leaving only an internal portion exposed to the vascular wall. Electrodes 302 are coupled to multi-channel wire 304 through spine 317. The spine 317 also acts as a tether for the edges 316 of the support collar 312, which does not include the electrodes since their function is to provide support. The functions of the multiple channel electrode 302 discussed with reference to Figures 25-28 are equally applicable to this embodiment.

The ends of ridges 316 may be connected (eg, sutured) after being arranged around an arter ia carotid, or may remain open as shown. If the ends remain open, the ridges 316 can be formed of a relatively soft material to ensure mechanical protection around the carotid artery. For example, edges 316 can be formed of polyethylene, polypropylene, PTFE, or other similar insulating and biocompatible material. Alternatively, the edges 316 can be formed of a metal such as stainless steel or a nickel titanium alloy, as long as the metallic material is electrically isolated from the electrodes 302. As a further alternative, the ridges 316 may comprise an insulating and biocompatible polymeric material with the structural integrity provided by the metal reinforcement (eg, stainless steel, nickel titanium alloy, etc.). In the latter alternative, the electrodes 302 may comprise the metallic reinforcement.

Reference is now made to Figure 31 which illustrates a schematic It is just a specific example of an electrode device for an extravascular electrical actuator 300. In this specific example, the base structure 306 comprises a silicone sheet that has a length of 5.0 inches, a thickness of 0.007 inches, and a width of 0.312 inches. Electrodes 302 comprise a platinum ribbon having a length of 0.47 inches, a thickness of 0.0005 inches, and a width of 0.040 inches. Electrodes 302 are adhesively connected to one side of silicone sheet 306.

Electrodes 302 are connected to a lead from a modified bipolar endocardial pacemaker, available under the trade name CONIFIX from Innomedica (now BIOMEC Cardiovascular, Inc.), model number 501112. The proximal end of lead 304 is connected to control system 60 or to impeller 66 as previously described. The pacemaker lead is modified by removing the lead from the pacemaker to form the cable body 304. The MP35 wires are pulled from the distal end thereof to form two wires 318 positioned side by side with a diameter of approximately 0.020 inches. The wires 318 are then connected to the electrodes using 316 stainless steel clamp terminals laser welded to one end of the platinum electrodes 302. The distal end of the cable 304 and the connection between the wires 318 and the ends of the electrodes 302 They are encapsulated in silicone.

The cable 304 illustrated in Figure 31 comprises a coaxial type cable that includes two coaxially arranged wire cables spaced apart on two separate wires 318 for joining with the electrodes 302. A construction of

Alternative cable 304 is illustrated in Figure 32. Figure 32 illustrates an alternative cable body 304 that may be formed in a curvilinear shape such as a sinus configuration, prior to implantation. The co Curvilinear configuration readily accommodates a change in distance between device 300 and control system 60 or driver 66. Such a change in distance can be encountered during flexion and / or extension of the patient's neck after implantation.

In this alternative embodiment, the cable body may comprise two or more conductive wires 304a arranged coaxially or collinearly as shown. Each conductive wire 304a may comprise a multifilament structure of suitable conductive material such as stainless steel or MP35N. An insulating material can surround the wire conductors 304a individually and / or collectively. For purposes of illustration only, a pair of electrically conductive wires 304a is shown having an insulating material that surrounds each wire 304a individually. The insulated wires 304a can be connected by a spacer 304b comprising, for example, an insulating material. A ca Additional mass of suitable insulating material may surround each of the conductors 304a. The insulating jacket may be shaped to have the same curvilinear shape as the insulated wires 304a to help maintain the shape of the cable body 304 during implantation.

If a sinusoidal configuration is chosen for the curvilinear shape, the amplitude (A) can range from 1mm to 10mm and preferably ranges from 2mm to 3mm. The wavelength (WL) of the sinusoid can vary from 2mm to 20mm, preferably it ranges from 4mm to 10mm. The curvilinear or sinusoidal shape can be formed by a heated process, using an arrangement that holds the wire 304 in the desired shape while the wire is exposed to heat. Sufficient heat is used to heat the conductive wires 304 and / or the surrounding insulating material. After cooling, the wire 304 can be removed from the device, and the wire 304 maintains the desired shape.

If a sinusoidal configuration is chosen for the curvilinear shape, the amplitude (A) may range from 1mm to 10mm, and preferably ranges from 2mm to 3mm. The wavelength (WL) of the sinusoid can range from 2mm to 20mm, and preferably ranges from 4mm to 10mm. The curvilinear or sinusoidal shape can be formed by a heating definition procedure that uses a device that holds the wire 304 in the desired shape while the wire is exposed to heat. Sufficient heat is used to heat the conductive wires 304a and / or the surrounding insulating material. After cooling, the wire 304 can be removed from the device, and the wire 304 retains the desired shape.

To attack low blood pressure and other conditions that require increased blood pressure, some of the previously described baroreceptor activation devices can be used to selectively and c blood pressure can be controlled by inhibiting or damping baroreceptor signals. By selectively and controllably inhibiting or damping baroreceptor signals, the present invention reduces the conditions associated with low blood pressure as previously described. Specifically, this would work to increase blood pressure and the level of activation of the sympathetic nervous system by inhibiting or damping the activation of baroreceptors.

This can be accomplished using mechanical, thermal, electrical, and chemical or biological means. Mechanical means can be triggered from the pressure pulse of the heart to mechanically limit the deformation of the arterial wall. For example, any of the previously described 120/160 external compression devices can be used to limit deformation of the arterial wall. Alternatively, the external compression device may limit Simply put the diametrical expansion of the vascular wall adjacent to the baroreceptors without the need for a trigger or control signal.

Thermal means can be used to cool the baroreceptors 30 and adjacent tissue to reduce the response of the baroreceptors and therefore dampen the signals from the baroreceptors. Specifically, the signals from the baroreceptor 30 can be damped either by directly cooling the baroreceptors 30, to reduce their sensitivity, metabolic activity and function, or by cooling the surrounding vascular wall tissue thereby causing the wall to be less responsive to increases in blood pressure. An example of this modality is using the cooling effect of the Peltier 340 device. Specifically, the heat transfer junction 347 can be positioned adjacent the vascular wall to provide a cooling effect. The cooling effect can be used to dampen signals generated by baroreceptors 30. Another example of this embodiment is using fluid delivery device 260 to deliver a cold or icy fluid (eg, saline). In this arrangement, the driver 66 would include a heat exchanger to cool the fluid and the control system 60 can be used to regulate the temperature of the fluid, thereby regulating the degree of damping of the signal from the baroreceptor 30.

Electrical means can be used to inhibit activation of baroreceptor 30 by, for example, hyperpolarization of cells at or near baroreceptors 30. Examples of cell hyperpolarization devices and methods are described in U.S. Patent No. 5,814,079 Kieval, and US Patent No. 5,800,464 to Kieval. Such electrical means can be implemented using any of the arrangements discussed with reference to Figures 13-18 and 21. <

Chemical or biological means can be used to reduce the sensitivity of the baroreceptors 30. For example, a substance that reduces the sensitivity of the baroreceptors can be administered using the device.

ES 2 330 833 T3 fluid administration 260 previously described. The desensitizing agent may comprise, for example, tetrodotoxin or other excitable tissue inhibitor. From the foregoing, it should be apparent to those skilled in the art that the disclosure provides a number of devices, systems, and methods by which blood pressure, nervous system activity, and neurohormonal activity can be selectively regulated and Controllable by activating baroreceptors or inhibiting / damping baroreceptor signals. It can be used to increase or decrease blood pressure, sympathetic nervous system activity, and neurohormonal activity, as required for mini mize harmful effects on the heart, vascular system, and other organs and tissues.

The previously described baroreceptor activation devices can also be used to provide antiarrhythmic effects. It is well known that the myocardial susceptibility to the development of conduction disturbances and malignant cardiac arrhythmias is influenced by the balance between stimulation of the sympathetic and parasympathetic nervous systems to the heart. That is, elevated sympathetic nervous system activation, coupled with decreased parasympathetic system stimulation, increases myocardial irritability and the likelihood of arrhythmia. Thus, by decreasing the level of activation of the sympathetic nervous system and improving the level of activation of the parasympathetic, the devices, systems and methods of the present invention can be used to provide a protective effect against the development of conduction disturbances. cardiac ion.

For each of those applications, it may be desirable to focus the results of the activation device 70 on portions of the carotid sinus 20 that are rich in baroreceptors 30, and minimize the results delivered to portions of the carotid sinus 20 with little or no baroreceptor 30. By focusing the results in such a way, the activation of the baroreceptors can be maximized and the required output device (that is, the required output power or energy of the baroreceptor activation device 70) can be minimized. In particular, the rate of baroreceptor activation at device output (A / O) can be maximized. Furthermore, by focusing the output as such, the activation of foreign tissues can be minimized, energy consumption (by device 70) can be minimized, and the rate of degradation of the baroreceptor response can be minimized.

It has been found that the proportion On A / O is a function of the position of the baroreceptor activation device. In particular, the A / O ratio has been found to vary around the circumference of the carotid artery near the carotid sinus 20, perhaps due to variations in the location or density of the baroreceptors. Although described herein with reference to the carotid sinus 20, the A / O ratio is also likely to vary across all anatomical locations containing baroreceptors as previously described.

In order to position the baroreceptor activation device 70 to maximize the A / O ratio, a mapping technique can be employed. For example, device 70 can be oriented in two or more different positions and / or in two or more different anatomical locations. More specifically, the outlet means of device 70 may be arranged in two or more different positions / locations. The means of egress are generally refer to the structure through which the stimulus is transferred to the tissue surrounding the baroreceptors. In electrical drive embodiments, for example, the output means may comprise electrodes.

At each position / location, device 70 can be activated to a specified level, and the degree of activation of the baroreceptor can be observed or measured. The degree of baroreceptor activation can be determined interferentially by measuring changes in heart rate, blood pressure, and / or other physiological parameters indicative of baroreceptor activation. The resulting measurements can be used to generate an A / O ratio for each position / location. The A / O ratios for each location can be drawn graphically to generate a map. The A / O ratios can be compared, and the position / location that has the most desirable A / O ratio can be selected for the device. itive 70. To illustrate the mapping method, you can refer to Figures 33-35. By way of example, not limiting, the mapping method is described with specific reference to arteries, but the method is equally applicable to all anatomical structures that contain baroreceptors. Figure 33 shows the right carotid arteries including the common 14, internal 18 and external 19 arteries. The carotid sinus 20 can be highlighted by a bulge 21, which typically extends from the common carotid artery 14 to the internal carotid artery 18 near the bifurcation. The carotid sinus 20 contains a significant number of baroreceptors, the number and density of which can vary around the circumference and along the length of the sinus 20. As such it is desirable to determine the optimal position of the baroreceptor activation device 70, both in terms of circumferential and longitudinal position.

The map method eo described herein is equally applicable to all baroreceptor activation devices 70 regardless of the mode of activation (mechanical, electrical, thermal, chemical, biological, or other means) and regardless of their position in vivo (intravascular, extravascular, intramoral). By way of example, not limitation, device 70 is shown in Figure 34 as an extravascular electrical device 500 having two electrodes 520 that contact the outer wall of carotid sinus 20 at two different locations. Device 500 includes a molded silicone shell 512. The housing 512 carries two metal strips 510 that are spaced approximately 4mm apart and are formed of platinum tape (0.040 inch wide by 0.0005 inch thick by 10mm long). The metal strips 510 are insulated by the housing 502 except in the exposed 1 mm wide area 516. The metal strips 510 in the exposed area 516 define two electr ears 520 that come into contact with the outer surface of the carotid artery. Cables 514 couple metal strips 510 to cable 502 which is connected to a control system 60 as previously described with reference to Figure 3.

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With device 500 disposed around the carotid arteries as shown in Figure 34, device 500 can be activated to produce an output signal from electrodes 520, which in turn activates the baroreceptors, as evidenced by a change in heart rate and / or blood pressure. The position and / or location of the electrodes 520 is recorded along with the amount of output (eg power) and the corresponding change in heart rate, blood pressure and / or other physiological parameters indicative of activation of the baroreceptors. From this information, the A / O ratio can be determined for this position / location. particular.

Electrodes 520 of device 500 are then oriented in a different position (eg, by rotation) and / or placed in a different anatomical location, and the same measurements are made. These steps are repeated to collect the desired amount of data, which can be drawn graphically to generate a map in order to determine an optimal position / location. The A / O ratios can be compared, and the position / location that has the most desirable A / O ratio can be selected for device 500. As an alternative to device 500, a handheld probe or similar device can be used that incorporate 520 electrodes to allow easier handling and quicker changes between different locations / positions.

In order to keep track of the circumferential positions around the carotid arteries, a coordinate system such as the one s e shown in Figure 35. Figure 35 is a schematic cross-sectional view taken along line 35-35 in Figure 34, showing a mapping coordinate system for the left carotid artery 15 and the right carotid artery 14 . In this coordinate system, the left carotid artery 15 and the right carotid artery 14 are viewed in cross section looking from the patient's head toward the feet, with zero degrees of positioning anteriorly and 180 ° of positioning posteriorly. The center or apex of the left pons 21L identifying the left carotid sinus 20L is typically located at 110 ° to 160 °. The center or apex of the right pons 21R identifying the right carotid sinus 20R is typically located at 200 ° to 250 °. This coordinate system is particularly useful for mapping the circumference of the carotid arteries, as well as other tubular arteries and organs.

In order to i To further lighten this method, an animal experiment using device 500 was carried out on the left and right carotid arteries of an animal. Device 500 was wrapped around the carotid artery near the carotid sinus 20 at the bifurcation of the internal 18 and external 19 carotid arteries, substantially as shown in Figure 34. Using the coordinate system described with reference to Figure 35, the center of the pons 21L of the left carotid sinus 20L for this animal was located at 120 °, and the center of the pons 21R of the right carotid sinus 20R was located at 200 °. .

Electrodes 520 were rotated around the left carotid artery at 90 °, 120 °, 180 °, and 270 ° positions. Electrodes 520 were rotated around the right carotid artery at positions at 155 °, 180 °, 200 °, 220 °, and .255 °. At each position, the 520 electrodes were activated by a 4 volt signal. ios, and mean arterial pressure (MAP) and heart rate (HR) were measured. The data on the right side is graphically illustrated in Figure 36 and the data on the left side is graphically illustrated in Figure 37.

These data suggest that the response (that is, the degree of activation of the baroreceptors) is inhomogeneous and unpredictable around the circumference of the carotid arteries. However, from these data, it is possible to locate both hot spots (large A / O ratio) and dead spots (low A / O ratio) around the circumference of the carotid arteries. For example, on the right side, there appears to be a dead zone at 355 ° and 180 ° and a dead center around 255 °. Also on the right side, there appears to be a hot zone at 390 ° and 220 °. On the left side, there appears to be a hot zone from 90 ° to 180 °, and a dead center near 270 °. Thus, there is a variability of the A / O ratio around the circumference of the carotid arteries, between the right and left sides, and probably between patients. Due to this variability, the mapping method described here may be beneficial in positioning the baroreceptor activation device for an optimal A / O ratio.

It is also contemplated that device 500 may have many individually controllable electrodes 520 disposed around a large area of ​​the carotid sinus (eg, around the entire circumference), as described elsewhere herein. Electrodes 520 can be activated individually, and the corresponding baroreceptor response for each electrode can be determined. Electrodes 520 having the most desirable A / O ratios can then be selected for chronic use. This method negates the need to reposition or relocate the device to find the optimal A / O ratio. This method also allows the selection of the electrodes are changed after implantation without the need to change the position / location of the device 500 in a subsequent clinical procedure.

Those skilled in the art will recognize that the present invention may manifest itself in a variety of ways other than the specific embodiments described and contemplated herein. Accordingly, differences in shape and detail can be made without departing from the present invention as described in the appended claims.