Ultraminiature integrated cardiac pacemaker and distributed pacing system

ULTRA MINIATURE INTEGRATED CARDIAC PACEMAKER AND : DISTRIBUTED CARDIAC PACING SYSTEM

BACKGROUND OF THE INVENTION . ,

FIELD OF THE INVENTION ׳ י'< '

The present invention concerns an ultra miniature integrated pardiac pacemaker and :

distributed cardiac pacing system. The invention provides an ultra miniature integrated . cardiac pacemaker and distributed cardiac pacing system that allows pacing of the heart . without the need for conventional lead wires that connect the electrodes and the main body, of the pacemaker, and allows implantation by catheter manipulation wi(hout incising :the chest wall, which avoids imposing an extra burden on the user.

In this invention, “ultra miniature” refers to the minute size of the pacemakeftp the extent that it can be attached to the tip of a catheter.

DESCRIPTION OF RELATED ART '.:.'

A cardiac pacemaker is a device that controls the rhythm of the heart by detiveiiiig electrical impulses to the heart, and is indicated for use in patients with, symptoms of.: ׳ ״ bradyarrhythmia.

A conventional cardiac pacemaker includes the main body of the cardiac pacpriiaker׳ (generator), lead wires, and electrodes that transmit a stimulating pulse to the myocardium; The main body of the cardiac pacemaker and the electrodes are connected by lead wires.

However, conventional pacemakers have the following problems.

Since the main body of the cardiac pacemaker and the electrodes are connected׳ by lead wires, cases of breaking of the lead wires have occurred. Breakage^ the lead wires results in defective pacing. In addition, there have been also cases of venous obstruction by the lead wires.

Moreover, during the early stages after implantation of the cardiac pacemaker, a shift in position of the electrodes may cause defective pacing. When a shift in posilion of

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the electrodes occurs, a second operation has to be performed, which adds .extra strain for ן the patient.

Furthermore, if there is a defective hermetic sealing structure at the junction between . the cardiac pacemaker main body and the lead wires, this may lead to defective pacemaker 5 movement. Problems with electrical safety have also occurred.

In the Unexamined Japanese Patent Publication Heisei No. 5245215־, !.cardiac pacemaker is described in which the signals for cardiac stimulation are delivered from the cardiac pacemaker main body to the stimulation electrodes by wireless transmission, thus eliminating the lead wires between the cardiac pacemaker main body and the electrodes.

However, even for this type of cardiac: pacemaker, surgical implantation of the pacemaker cannot be avoided, and there have been cases in which skin necrosis occurred ; at the cardiac pacemaker implantation site.

Also, in the above-mentioned cardiac pacemaker, although wireless communication is conducted between the pacemaker main body and the electrodes, there is no communication between the electrodes. Synchrony between the multiple electrodes being: used is controlled by the pacemaker main body.

The present invention was developed in order to solve the above problems, and 10 provide an ultra miniature integrated cardiac pacemaker and distributed, cardiac pacing system with the following features: the generator function of electee stimulus by the 20 pacemaker main body is integrated with the electrodes, thus allowing pacing of the heart without the need for conventional lead wires connecting the electrodes .and pacemaker main body. By integrating the control unit of the pacemaker main body and the electrodes, there is no need to implant the pacemaker main body, which avoids imposing an extra burden on the user.

SUMMARY OF THE INVENTION

The ultra miniature integrated cardiac pacemaker of the.present.invention requires no chest incision, and is implanted in the heart׳ by attaching it to the tip. of a catheter and extracting the catheter after implanting.

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In one; embodiment, the pacemaker includes a control unit that outfits control signals, a heart stimulating means that responds to the control signal and electrically stimulates the heart tissue, an eleetrocardiogrtphic information detecting fneahs that detects the electrocardiographic information and outputs it to the control unit, and a power unit that supplies the driving power.

The control unit outputs the control signals based on electrocardiographic information.

The power unit is preferably a biological fuel cell that extracts electrons from oxidative reactions of biological fuels. The biological fuel cell is composed of an anode electrode and a cathode electrode. The anode electrode is coated with immobilized oxidative enzymes for biological fuels and mediators. The biological fuel cell uses blood and/or body fluid as an electrolyte solution and utilizes biological fuels and oxygen in blood and/or body fluid.

In another embodiment of the present invention, an ultra miniature integrated cardiac 15 pacemaker includes a control unit that outputs control signals, a heart stimulating means that responds to the control signal and electrically stimulates the heart tissue, an electrocardiographic information detecting means that detects the electrocardiographic information and outputs it to the control unit, a transmitting means that modulates the electrocardiographic information and control signals to be sent outside, and a power unit 20 that supplies the driving power.

The control unit outputs the control signals based on electrocardiographic information.

The power unit is preferably a biological fuel cell that extracts elections from oxidative reactions of biological fuels. The biological feel cell is composed of an anode 25 electrode and a cathode electrode. The anode electrode is coated with immobilized oxidative enzymes for biological feels and mediators. The biological feel cell uses blood and/or body fluid as an electrolyte solution and utilizes biological feels and oxygen in blood and/or body fluid.

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In a third embodiment, an ultra miniature integrated cardiac paeema^w inpluties a control unit that outputs control signals, a heart stimulating means that responds, to the control signal and electrically stimulates the heart tissue, an electrocardiographic / information detecting means that detects the electrocardiographic information and outputs 5 it to the control unit, a receiving means that receives and demodulates the infotmatron sent 60m outside, and a power unit that supplies the driving power. It is designed such that the information sent from outside is input into the control unit.

The control unit outputs control signals based on information sent from outside and/or electrocardiographic information.

The power unit is preferably a biological fuel cell that extracts electrons from oxidative reactions of biological fuels. The biological fuel cell is composed of an anode electrode and a cathode electrode. The anode electrode is coated with immobilized oxidative enzymes for biological fuels and mediators. The biological fuel cell uses.blood and/or body fluid as an electrolyte solution and utilizes biological fuels and oxygen, in blood and/or body fluid.

In yet another embodiment, an ultra miniature integrated cardiac pacemaker includes a control unit that outputs control signals, a heart stimulating means that responds 10 the control signal and electrically stimulates the heart tissue, an electrocardiographic information detecting means that detects the electrocardiographic information and outputs 20 it to the control unit, a transmitting means that modulates the electrocardiographic information and control signals to be sent outside, a receiving means that receives and demodulates the information sent from outside, and a power unit that supplies the driving current. It is designed such that the information sent from outside is input into the control unit.

The control unit outputs control signals based on information sent from outside and/or electrocardiographic information.

The power unit is preferably a biological fuel cell that extracts electrons from oxidative reactions of biological fuels. The biological fuel cell is composed of an anode electrode and a cathode electrode. The anode electrode is coated with immobiliied

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>ללכלו(43 2005-01-24 16:01 FROM oxidative «ray־.« for bioio^f־ ־!־״nd m־<u־t־ra. n־bi10־gi־am־־u^M־<־d _md/OT body fluid as electrolyte solution and utilizes Hologic«! Ms and ״xy₈״־ and/or body fluid.

Another embodiment discloses a cardiac pacing system ineluding an ultra miniature 5 integratedcardiacpacemakerplaoedintheatrialmyocardium.

Π» ultra miniature integrated cardiac pacemaker is equipped with a control unit that outputs control signals, a power unit that supplies die drivmg power, a heart stimuiatiti g means that responds to ihe cental signals and electrically stimulates lhe atrial myocardium, and an electrocardiographic information detecting means that detects the tO electrocardiographic information including at least intracardiac P wave information;

The power unit is preferably a biological fuel cell that extracts electrons from oxidative reactions of biological fads. The biological fitel cell is composed of an anode electrode and a cathode electrode. He anode electrode is coated with immobilized oxidative enzymes for biological fuels and mediators. The biological fiiel cell uses blood. 15 and/or body fluid as an electrolyte solution and utilizes biological fuels end oxygeii in blood and/or body fluid.

The control unit is equipped with a stimulation timing determining means that decides the timing of stimulation to generate control signals, and a stimulation timing changing means that changes the timing of stimulation to generate control signals. It !is 20 characterized by the ability to change the timing of stimulation to generate the control signal, in case intracardiac P wave information is detected within a preset time interval.

Yet another embodiment concerns a distributed cardiac pacing system incl tiding an electrocardiographic information detecting device placed in the atrial myocardium and an ultra miniature integrated cardiac pacemaker placed in the ventricular myocardium.

The electrocardiographic information detecting device is equipped with an electrocardiographic information detecting means that detects the electrocardiographic, information including at least intracardiac P wave information, a transmitting means that modulates the electrocardiographic information detected and sends the information to the ± w4־ TO 00101097236114101 P-51

200516:01 24־01־ FROM +3)^3970-.43:, AjJ ultra miniature integrated cardia־ pacemaker, and a power unit that , supplies the driving current

The power unit is preferably abidlogiaJ fuel cell that extracts electrons from oxidative reactions ofbiological ftels. Ute biological fuel cell is composed of ananbde 5 electrode and a cathode electrode. The anode electrode is coated with immobilized oxidative enzymes for biological fods ־nd mediators. The biological foel cell uses blood and/or body fluid as an electrolyte solution and utilizes biological fuels and oxygen in blood and/or body fluid.

The ultra miniature integrated cardiac pacemaker is equipped with a receiving means 10 that receives and demodulates the electrocardiographic information sent from the electrocardiographic information detection device, a control unit that outputs control signals, a power unit that supplies the driving power, and a heart stimulating means that responds to the control signal and electrically stimulates the ventricular myocardium.

The power unit is preferably a biologidal foel cell that extracts elections from 15 oxidative reactions ofbiological fuels. The biological foci cell is composed ofan anode electrode and a cathode electrode. The anode electrode is coated with immobilized enzjroes for biological fuels and mediators, ־the biological fuel cell uses blood and/or body fluid as an electrolyte solution and utilizes biological fttels and oxygen in blood and/or body fluid.

The control unit is equipped with a stimulation timing determining means that .

decides the timing of stimulation to generate the control signals, and a stimulation timing changing means that changes the timing of stimulation to generate the control signals.

It is characterized by a mechanism to generate control signals when intracardiac . QRS complex information is not detected within a given time after the detection of 25 intracardiac P wave, and suppress the control signals when QRS comptex information is. detected within a given time after the detection of intracardiac P wave information.

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Another embodiment disoloset. distributed ־־rii־־ pacing ־ystent in!־l״di״g;a first: ₁dtra_Im₁>i»turai11tegra»i“^ltoP^Ket'^l^:’¹^^inte^^d^^M^^”*^l*^sp!Olliritra miniature integrated cardiac pacemaker placed in the ventricular myodutthunu

The first ultra miniature integrated cardiac pacemaker is equipped with a control umt. 5 that outputs control signals, a power unit that supplies the driving power, a heart : stimulating means that responds to the control signal and electrically stimulates the atrial myocardium, an electrocardiographic information detecting means that detects the electrocardiographic information including et least intracardiac P wave in&amp;rmatton, a transmitting means that modulates the electrocardiographic mfbrmation and sends*־ 10 information to the second ultra miniature integrated cardiac pacemaker, and a recriving means that receives and demodulates the electrocardiographic informations־»! from the second ultra miniature integrated cardiac pacemaker.

The power unit is preferably a biological fuel cell that extracts electrons from oxidative reactions of biological fuels. The biological fuel cell is composed of an anode.

electrode and a cathode electrode. The anode electrode is coated with, immobilized oxidative enzymes for biological fuels and mediators. The biological fiiel cell uses blood and/orbodyfluidasanelectrolytesoludonandutilizesbiologicaifuelsaridoxygenin blood and/or body fluid.

The electrocardiographic information sent from the second ultra minjature integrated 20 cardiac pacemaker is input into the control unit; and the control unit is equipped with a stimulation timing determining means that decides the timing of Stimulatidn to generate, the control signals, and a stimulation timing changing means that changes, the tuning of stimulation to generate the control signals.

The second ultra miniature integrated cardiac pacemaker is .equipped with a.control 25 unit that outputs control signals, a power unit that supplies the driving power, a heart stimulating means that responds to the control signal and electrically stimulates the ventricular myocardium, an electrocardiographic information detecting means that detects the electrocardiographic information including at least intracardiac QRS complex information, a transmitting means that modulates the electrocardiographic information and 30 sends the information to the first ultra miniature integrated cardiac pacemaker, and a

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P.53 receiving means that r«eives anti demodulates theeleclrocardiographicinfonntuion sent by the first ultra miniature integrated cardiac pacemaker.

The power unit is preferably a biological fbel cell that extracts electro»־ from oxidative reactions of biological fbels. The biological firel ־*11«־ electrode and a cathode electrode. The anode electrode is coaled with immobilized oxidative enzymes for biological fuels and mediators. The biological fuel «11 uses blood, and/or body fluid as electrolyte solution and utilizes biological fuels and oxygen ®blood and/or body fluid.

The electrocardiographic information sent from the first ultra miniature integrated 10 cardiac pacemaker is input into the control unit, and the control unit is equipped with a stimulation timing determining means that decides the timing of stimulation to generate the control signal, and a stimulation timing changing means that changes the timingof stimulation to generate the control signal.

The control unit of the first ultra miniature integrated cardiac pacemaker .generates 15 the control signa! when intracardiac P wave information is not detected within a given time interval, and suppresses the generation of control signals when intracardiac P Wave information is detected within a given time.

The control unit of the second ultra miniature integrated cardiac pacemaker &lt; generates control signals, when intracardiac QRS complex information is not detected 20 within a given time after detection of intracardiac P wave information, arid suppresses the generation of control signals when intracardiac QRS complex information is. detected within a given time after detection of intracardiac P wave information.

The system is also characterized by the following mechanism: if the second Ultra miniature integrated cardiac pacemaker detects intracardiac QRS complex information due 25 to spontaneous ventricular contraction, the control unit of the first ultra miniature integrated cardiac pacemaker suppresses the detection of intracardiac P wave itfortnatiori for a given time interval.

Another embodiment discloses a. distributed cardiac pacing system including!an electrocardiographic information detection device placed in the atrial myocardium and

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P.54 • 9 multiple ultra miniature integrated cardiac pacemakers placed in the ventricular myocardium.

The electrocardiographic information detection device is equipped with an electrocardiographic information detectingmeans that detects the electrocardiographic information including at least intracardiac P wave infoimation, a transmitting means that modulates the detected electrocardiographic information and sends the information to. the ultra miniature integrated cardiac pacemakers, and a power unit that supplies the driving power.

The power unit is preferably a biological: fuel cell that extracts electrons' from ;

oxidative reactions of biological fuels. The biological fuel cell is composed of an'anode electrode and a cathode electrode. The anode electrode is coated with immobilized oxidative enzymes for biological fuels and mediators. The biological fuel cell uses blood and/or body fluid as electrolyte solution and utilizes biological fuels, and oxygen in bl ood and/or body fluid.

The nltp miniature integrated cardiac pafcemakers are equipped with a control unit that outputs control signals, a power unit that supplies the driving power, a heart ¹stimulating means that responds to the' control signals and electrically stimulates the ventricular muscle, an electrocardiographic information detecting means that detects the electrocardiographic information including at least intracardiac QRS complex information,^: a transmitting means that modulates the electrocardiographic information and sends the information to other ultra miniature integrated cardiac pacemakers, and a receiving means that receives and demodulates the electrocardiographic information sent from other ultra miniature integrated cardiac pacemakers.

The power unit is preferably a biological fuel cell that.extracts electrons from oxidative reactions of biological fuels. The biological fuel cell is composed of ־an. anode electrode and a cathode electrode, The anode electrode is coated with immobilized oxidative enzymes for biological fuels and mediators. The biological fuel pell uses blood and/or body fluid as an electrolyte solution and utilizes biological fuels and׳ oxygen in blood and/or body fluid. .

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The electrocardiographic information sent from other ultra miniature integrated cardiac pacemakers is input into the control unit; and the control unit is equipped With .a« stimulation timing determining means that decides the timing of stimulation to generate the control signals, and a stimulation timing changing means that changes the tuning of stimulation to generate the control signals.

The system is characterized by the following mechanism: when individual ultra miniature integrated cardiac pacemakers do.hot detect intracardiac QRS complex infonnation within the respective preset times after detection of intracardiac P wave information, the control units ofthe ultra miniature integrated cardiac pacemakers generate control signals; whereas when QRS complex information is detected within given time intervals after detection of intracardiac P wave information, the control units generate control signals synchronous to the earliest timing at which the intracardiac QRS complex information is first detected.

Yet another embodiment discloses a distributed cardiac pacing system including a first ultra miniature integrated cardiac pacemaker placed in the atrial myocardium and multiple second ultra miniature integrated cardiac pacemakers placed in. the ventricular myocardium.

The first ultra miniature integrated cardiac pacemaker is equipped with a control unit that outputs control signals, a power unit that supplies the driving power, a lieart stimulating means that responds to the control signals and electrically stimulates the atrial myocardium, an electrocardiographic information detecting means that detects the electrocardiographic information including at least intracardiac P wave information, a transmitting means that modulates the electrocardiographic information and sends the infonnation to multiple second ultra miniature cardiac pacemakers, and a receiving means that receives and demodulates the electrocardiographic information sent by the multiple second ultra miniature integrated cardiac pacemakers.

The power unit is preferably a biological fuel cell that extracts_:electrotis from oxidative reactions of biological fuels. The biological fuel cell is composed ©fan anode electrode and a cathode electrode. The anode electrode is coated with immobilized oxidative enzymes for biological fuels and mediators. The biological fuel cell.uses blobd

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The electrocardiographic information sent from the multiple second ultra miniature integrated cardiac pacemakers are input into the confrol unit; and the control. unit is . ^; equipped with a stimulation timing determining means that decides the timing of stimulation to generate the control signals, and a stimulation timing changing means that changes the timing of stimulation to generate the control signals.

The multiple second ultra miniature integrated cardiac pacemakers are each equipped with a control unit that outputs control signals, a power unit that supples׳ the 10 driving current, a heart stimulating means that responds to the control signal and electrically stimulates the ventricular myocardium, an electrocardiographic information detecting means that detects the electrocardiographic information including at least intracardiac QRS complexes, a transmitting means that modulates the electrocardiographic information and sends the information to the first and other second ultra miniature cardiac 15 pacemakers, and a receiving means that receives and demodulates the electrocardiographic information sent from the first and other second ultra miniature integrated cardiac pacemakers.

The power unit is preferably a biological fuel cell that extracts elections from oxidative reactions of biological fuels. The biological fuel cell is composed of .an anode 20 electrode and a cathode electrode. The anode electrode is coated with immobilized oxidative enzymes for biological fuels and mediators. The biological fuel cell uses blood and/or body fluid as an electrolyte solution and utilizes biological fuels and oxygen in blood and/or body fluid.

The electrocardiographic information sent from the first and other second ultra . 25 miniature integrated cardiac pacemakers is input into the control unit;, and the control unit is equipped with a stimulation timing determining means that decides the tinting of stimulation to generate the control signals, and a stimulation timing changing means that changes the timing of stimulation to generate the control signals.

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The control unit of foe firat ultra mimatm . .

control signals when intracardiac P wav־ information is not detected within:־; givon tim־ interval, and suppresses the generation of control signal when intracardiac P. wave information is detected within a given time.

The control units of the second ultra miniature integrated cardiac pacemakers, generate control signals when intracardiac QRS complex infonnatio״ is not detected by individual ultra miniature integrated cardiac pacemakers within the respective, preset time. intervalsafterthedetecttonofintracardiMP weit*rmation;whereasifintrac־d^ QRS complex information is detected within the given time intervals after the detection of intracardiac P wave information, the control units generate control signals synchronous to the ..11^ timing at which intracardiac QRS complex infomation is. detected.

The system is also characterized by the following mechanism: when tae ofthe multiple second ultra miniature integrated cardiac pacemakers detects intracardiac QRS complex information due to apontaneous ventricular contraction, the control ״»it of the fhst ultra miniature integrated cardiac pacemaker suppresses the detection of intracardiac

P wave information for a given interval.

BRIEF DESCRiPTION⁵ OF THE DRAWINGS

Figure 1 is a .simplified block diagram of an ultra miniature integrated cardiac pacemalcer . in accordance with the first embodiment.

Figure 2 is a simplified block diagram of an ultra miniature integrated catdiac pawmakfer in accordance with the first embodiment.

Figure 3 b a simplified block diagram of an dtra miniature integrated ,cardiac pacemaker in accordance with the second embodiment

Figure4isasimplified block diagram of ah uitraminiaturemtegrated.cardipcpacemaker' in accordance with the third embodiment

Figure 5 is a simplified block diagram of an ultra miniature integrated cardiac pae'emaker in accordance with the fourth embodiment

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Figure 6 is a schematic diagram Ulustrating a fest application of the ultra'muualur^ integrated cardiac pacemaker in accordance with the present invention {the first distributed cardiac pacing system).

Figure 7 is a schematic diagram Ulustrating a second application ofthe ultra miniature .

eawHac pacemaker in accordance with the present invention (the second distributed cardiac pacing system).

Figure 8 is a block diagram illustrating an outline of the electrocardiographic information detection device.

Figure 9 is a schematic diagramUlustating a.tMrd appUcation of the ultra miniature o integrated cardiac pacemaker in accordance with the present invention (the third distributed cardiac pacing system).

Figure 10 is aschematic diagram illustrating a fourth application of the ultra niniipre integrated cardiac pacemaker in accordance with the present invention (the fourth > distributed cardiac pacing system).

₁₅ DETAILED DESCRIPTION OF THE INVENTION

The prcsent invention is described in detail below while referring to the figures. Figure 1 is a simplified block diagram of an ultra miniature integrated cardiac pacemaker (100) in accordance with a first embodiment of this invention.

The ultra miniature integrated cardiac pacemaker (100) in this embodiment is 20 composed of a control unit (2) that outputs control signals, a heart stimulating means (3) that responds to the control signals and electrically stimulates the heart tissue, an electrocardiographic information detecting means (5) that detects the electrocardiographic information and outputs it to the control unit (2), a transmitting means (10) that modulates the control signals output from the control unit (2) and/or electrocardiographic inionnation 25 detected by the electrocardiographic information detecting means (5) arid sends the information outside, a receiving means (9) that receives and demodulates rhe information sent from outside, and a power unit (4) that supplies the driving current.

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The heart stimulating means (3) responds to the control signal output &amp;om the control unit (2) and electrically stimulates the heart tissue. The heart stirnul4tirig means (3) as shown in the diagram is able to stimulate the heart tissue. The heart stimulating mearis (3) includes a stimulating unit (31) that responds to the control signals output from the 5 control unit (2) and outputs heart stimulating pulses to stimulate the heart-tissue, and two heart stimulating electrodes (32) that stimulate the heart tissue in response to the output pulses.

The electrocardiographic information detecting means (5) detects the electrocardiographic information at the site where the ultra miniature knegratedcardiac 10 pacemaker is placed. The detected electrocardiographic information^ output to: the ' control unit (2). The electrocardiographic information detected by the electrocardiographic information detecting means (5) includes P wave information, QRS complex information, T wave information, or Q-T time, A-H time, H-V time (where A is atrial potential, H is His bundle potential, and V is ventricular potential).

The electrocardiographic information detecting means (5) as shown in the, diagram is composed of two electrocardiographic information recording electrodes (5 3 ) that detect the applied site electrocardiographic information at the placement site; an amplifying unit (51) that amplifies the electrocardiogram, and an A/D conversion (52) unit that converts the detected electrocardiographic information into digital signals. The :

electrocardiographic information detecting means (5) is designed such that the converted electrocardiographic information is output to the control unit (2).

The transmitting means (10) is composed'of a modulating unit (11) that mputs and modulates the control signals output from the control unit (2) and/or electrocardiographic information, and a transmitting unit (12) that sends the modulated control signal's to the 25 outside via carrier waves; by which the modulated control signals are sent to the outside (such as to other ultra miniature integrated cardiac pacemakers, not shown in the diagram).

By transmitting control signals and electrocardiographic information via;gamer waves to outside sites such as other cardiac pacemakers, it is possible, for example, 10 activate two or more cardiac pacemakers synchronously. Moreover, since carrier waves

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P.60 are used for transmission, there is no

' 15

יו. . ' • need for lead wires, and this method avoids imposing an extra burden on the user.

n־ receivmg mass (9)« ^{of a}⁹¹⁾'״^{) totreC־lVeS}: .

infotmation transmitted from the outside via ־־frier waves, and ־ demodulating umt ¢92) that demodulates the information received. It ״.designed such that the demodulated information is input into the control unit (2). Based on this infonnati־־ and/or electrocardiographic infonnatton, control signals are generated in the control u״n (2) and output to the heart stimulating means (3).

The information transmitted ftom the outside includes electrocardiographic information and control signals sent 60m other cardiac pacemakera.

By equipping the receiving means (9) that receives infonnation from, for instance,, other cardiac pacemakers, it is possible to activate the cardiac pacemaker synchronously with other cardiac pacemakers. Moreover, since there is no need for lead wires, this method avoids imposing extra burden on the user.

Possible modes of communication between pacemakers executed^ the transmitting means (10) and receiving means (9) include, but are not limited to, spread spectrum communication using radio waves or ultrasound waves, and ultra wide band communication. There is no restriction on the mode of communication: Any method can be used as long as it provides reliable communication between pacemakers.

The power unit (4) is designed to supply a power source necessary to:drive the ultra miniature integrated cardiac pacemaker. As a power unit (4), in general, it is possible to.: use a lithium battery or fuel cells. However, in the conventional cardiac¹ pacemakers, the power unit that supplies the electrical source is the largest component. To hltra-miniattirize the cardiac pacemaker, it is necessary to miniaturize the power unit. For the ultra miniature integrated cardiac pacemaker (100) according to the present invention, a biological fuel cell is preferably used as the power unit (4).

If a biological fuel cell is used as the power unih biological fuels such as glucose and oxygen, which are necessary to drive the biological fuel cell, are available in constant supply inside the body. The volume of the power unit (4) depends only on the size of the

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One example ofabiologicalM cell used in this invention is the weit-known conventional biological M cell that extracts electrons &amp;om oxidative reactions of biological Ms. This biological M cell uses sugars (such as glucose) and oxygen, both supplied by the body, as Ms, and utilizes enzymes as biological catalysts.

An example ofthe composition ofthe preferable biological M cell .(40) for this invention will be explained by referring to the diagram. Figure 2 is a schematic diagram illustrating the simplified structure of the biological M cell (40) as the power unit in the ultra miniature integrated cardiac pacemaker (100) ofthe first embodiment.

The biological M cell (40) is composed of an anode (41) and a cathode (42). This biological M cell utilizes blood or body fluid as the electrolyte solution, and also utilizes sugars and oxygen in blood and body fluid as biological Ms. Therefore, the anode electrode (41a) and the cathode electrode (42a) are positioned so as to be in contact with blood or body fluid. In Figured the anode electrode (41a) and the.cathode electrode (42a) ared־si_gnedtob־incontectwithblood,andtheheanstimulating־lectrod32)־)andthe electrocardiographic information recording electrode (53) are in contact with the myocardial tissue.

Thc anode (41) is composed of an anode electrode (41a) and an immobile layer (41b) coating the surface of the anode electrode (41a). A gold electrode, etc/is preferably 25 used as the anode electrode (41a).

Oxidative enzymes of biological fuels and mediators necessary for the-oxidation of. biological fuels are immobilized on the surface of the anode electrode (41a) .

Carbohydrates are used as biological fuels. Examples of carbohydrates are monosaccharides such as glucose and fructose, disaccharides such as mannitol and sucrose x .״,״M/1 . 1.,:/.,־ TO 00101097236114101 Ρ.&amp;²

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and pentoses such as xylo־ ־־nd ־־™*־ז־ ^{which can be} body, is preferably used as the fuel.

Any oxidative enzymes tha oxidize biological fuels can be used in the present invention. For example, enzymes called oxidases and hydrogenases couldbe used. If 5 glucose is used as the biological fuel, glucose oxidase and glucose dehydrogenase can ־ used. Glucose dehydrogenase is preferable.

Any mediator that can transfer electrons released from the biological tel to the anode electrode (41a) can be used in the present invention. Some examples include, but are not limited to, the so-called coenzymas such as flavin adenine dinucleotide phosphate, 10 _enZymes such as laccase, quinines such as pyrrolo-quinoline quinine, andosmium complex, as well as their combinations.

The oxidative enzymes and mediators are immobilized on the surface of the anode electrode (41a) to form an immobile layer (41b). Brer־ is 0־ restriction on the method of. immobilization, and any method well known to immobilize enzymes onto »electrode 15 surface can be used. For example, ־ gold disc electrode can be used as the substrate, and aminoethane-thiol is adsorbed on the surface of the gold electrode to form a monomolecular film followed by modification of the amino groups. After that, the method mixes the oxidative enzyme for biological fuel, the mediator and albumin in a beaker. Then glutaraldehyde is added to allow the enzymes and mediators to cross-link with 20 glutaraldehyde and then the mixture is applied to the surface ofthe golddiscelcctrode.

To ensure that the reaction takes place efficiently at the anode, the immobile layer (41b) should preferably be designed such that the anode electrode (41a) doe not come into contact with oxygen present in the body.

The cathode (42) is composed of a cathode electrode (42a). An example of the 25 cathode electrode (42a) is a platinum electrode. A catalyst to enhance a reaction involving reduction ofoxygen is required on the cathode electrode (42a). The platinum itself can function as the catalyst.

To ensure that the reaction takes place efficiently at the cathode, it is desirable to fonn a coating (42b) on the surface ofthe cathode electrode, which willprevent

200506־16 24־01־ FROM +3153774 H+sD^ J TO 00101097236114101 P.63 : . I permeation ofsubstances other than oxygen that react with the cathode electrode (42a), and at the same time allow permeation of oxygen and hydrogen 10ns.

The biological fuel cell (40) does not have a container filled with electrolyte solution. Instead, the cathode electrode (4la) and the anode electrode (42a) are in contact: with lhe 5 blood or body fluid ofthe body. The blood and body fluid act as the electrolyte solution.

In the electrolyte solution, biological fuel and oxygen are constantly supplied by the Mood: flow, and at the same time metabolic products are dissolved in blood .and removed by the blood flow. The supply of biological fuel and oxygen as well as the removal of metabolic products are maintained constant through the mechanism of homeostasis.

Next, the action ofthe biological fuel cell (40) will be discussed.

Biological fuel is dissolved in blood and body fluid and supplied to the anode (41) surface. The biological fuel supplied to the anode (41) surface is oxidized by the action of. the biological fuel oxidative enzyme immobilized in the immobile layer (41b), producing carbon dioxide, hydrogen ion and intermediate metabolites, as well as electrons: Carbon 15 dioxide, hydrogen ion and intermediate metabolites are dissolved in blood or body fluid to be excreted. Electrons are transferred to the anode electrode (41 a) via mediators.

The cathode (42) surface is supplied with oxygen and hydrogen ions dissolved in blood and body fluid, and these ions react in the presence of electrons transmitted from the. anode electrode (41a) to the cathode electrode (42a), and form water. This reaction 20 generates an electric current, which is used as the driving power source.

Based on the program already saved in the memory (7) as well as on electrocardiographic information output from the electrocardiographic information detecting means (5) and information transmitted from the exterior, the control unit (2) generates control signals and outputs the signals into the heart stimulating means (3).

For instance, the control unit (2) is equipped with a stimulation timing determining means that decides the timing of stimulation to generate control signals, and.a stimulation. timing changing means that changes the timing of stimulation to generate, control signals. Usually this unit is programmed to generate control'signals at stimulation timing at a predetermined frequency. It is also programmed to change the stimulation timing when

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P.64 .

«*to conditions » Μ®«־ ~ ^P ״״* * detected within a given time interval.

Furthermore, this invention an be ־quippedwith ־ communication6) *״־־״־). The communication means (6) communicates with an extent־! programmer .(« insulted external to the ultra miniature integrated cardiac ?־־ .׳־*־־־־־־d >־< *> <־> <־־־״־ . pacing program saved in the memory (7). By .this means, even after rmplentat.01 ״־ th־ ultra miniature integrated cardiac pacemaker״־ the patient, it is possible to usethe Vernal programmer (8) to change the pacing program saved in the memory (7) as appropnate or the particular patient

For communication between the external programmer (8) and communication means (6) when a patient is implanted with multiple ultra miniature integrated cardiac pacemakers, by sening different ftequ־־!־־־ for the individual ultra miniature .־־״grated cardiac pacemakers, for example.«>״^{tog ρΓ}°^Ρ“ ^f0rminiature integrated cardiac pacemaker. Also, by conducting spread spectrum communication or by giving each pacemaker an ID, it is possible to change the pacing program of each ultraminiature integrated cardiac pacemaker.

Next, the ultra miniature integrated cardiac pacemaker of the second embodiment (110) of the present invention will be explained. The differ־־״־ between the ultra miniature integrated cardiac pacemaker in the second embodiment (110) and the aforementioned ultra miniature integrated catdiac pacemaker of the first embodiment (100) is that the former has no transmitting means (10) or receiving means (9).

The ultra miniature integrated cardiac pacemaker of the second embodiment (110) can be used when there is no need to synchronize movements with other cardiac pacemakers. י

Based on the control program already saved in the memory (7) and on , electrocardiographic infomtation output from the electrocardiographs־ information means (5), the control unit (2) generates control signals and outputs the s.gnals to the heart stimulating means (3).

*.־ע%'׳ככ+17 )׳??□07 FROM 43Π5־15 24־2005-01

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P.65 ׳rheothercomponentsarethesameasthoseintheaforementionedultramlniature integratedcardiacpacemakerofthefirstembbdiment(100),theref0reexplana1io1^are.: .

״*rad-toFtgraeJ,«״«.״^ the first embodiment (100) as shown in Figure 1.

Next, the ultra miniature integrated cardiac pacemaker of the third embodiment .

(120) of this invention will be explained. Fig4 ־־״ is a simplified block diagram of the ultra miniature integrated cardiac pacemaker in this embodiment (120): Ore difference. between the ultra miniature integrated cardiac pacemaker in this embodiment (120) and . the aforementioned ultra miniature integrated cardiac pacemaker of the firstembodiment.

o is that the former has no receiving means (9).

By sending the control signals to the exterior (such as other cardiac pacemakers) via carrier waves, the ultra miniature integrated cardiac pacemaker (120).is able tp synchronize and operate with, for instance, one or more other cardiac pacemakers.

Based on the control program already saVed in the memory (7) and electrocardiographic information output from the electrocardiographic information detecting means (5), the control unit (2) generates control signals and outputs the signals to the heart stimulating means (3).

The other components are the same as those in the aforemmtionedulira miniature integrated cardiac pacemaker of the first embodiment, therefore explanations areumitted: 20 In Figure 4, the same numbers are assigned to components identical to fliose.in the dltra ״inhere integrated cardiac pacemaker in accordance with the first and second embodiments shown in Figures 1 and 3.

Next, the ultra miniature integrated cardiac pacemaker of the fourth embodi ment (130) of this invention will be explained. The difference between the ultra miniature 25 integrated cardiac pacemaker in this embodiment (130) and the aforementioned ultra miniature integrated cardiac pacemaker in the first embodiment is that the foimef has no. transmitting means (10) to send control signals and/or electrocardiographic information to the exterior.

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Through the receiving means (9) that receives infonnation from theexteriorj for (130) is ־bl־ to synchronize ־nd operate with other c־rdi־c pacemakers. .

Based on the control program already saved in the memory (7), as well as / electrocardiographic i״fetmati־n output from the elecnocardiographrc mfonoatron detecting means (5) ״־d information transmitted tan the exterior, the control urn, (2) generates control signals and outputs the signals to the heart stimulating means (3)

Π» other components are the same as those in the aforementioned*־ miniature integrated cardiac pacemaker ofthe first embodiment, therefore explanations are tatted, in Figure 5, the same numbers are assigned to components identical to those in the ultra miniature integrated cardiac pacemakers in accordance with the first three embodiments shown in Figures 1,3 and 4.

In the ultra miniature integrated cardiac pacemakers of the first four embodiments, the electrocardiographic infonnation recording electrodes (53) and the heart stimtiatidg electrode (32) are shown as separate components. In reality, the electrocardiographic information recording electrode.(53) and the heart stimulating electrode (32) maybe shared.

Moreover, the receiving unit (91) and the transmitting unit (12) are shown bs separate components; however, the receiving unit (91) and the transmitting amt (12) may also be shared.

Furthermore, by installing in the patient'a sensor that measures body temperature and blood pressure and outputting the biological information obtained from these sensors to the control unit (2) ofthe ultra miniature integrated cardiac pacemakers ofthe first foiir embodiments, the control unit (2) is able to generate control signals based on the , . biological data.

In addition, for the ultra miniature integrated cardiac pacemakers Ofthe first four embodiments, there is no particular restriction on the method of implanting the pacemaker in the heart and conventional methods for catheterization may be adopted. For insane־, implantation may be done by attaching the ultra miniature integrated Cardiac pacemaker to

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the tip of a catheter and inserting it into the predetemined position inside the heart, and then withdrawing only the catheter after fixing the pacemaker in the endocardium. In the . ultra miniature integrated cardiac pacemakers of the invention, the generator main body . and the electrodes are integrated, thus obviating the need for lead wires. Therefore, the ultra miniature integrated cardiac pacemakers ofthe invention can be made of a size of only 2 to 3 mm in diameter. There is no need to make a wide incision in the chest wall to : implant the generator main body.

NexL a cardiac pacing system according to this invention using the aforementioned . ultra miniature integrated cardiac pacemakers in accordance with the first four embodiments of this invention will be described while referring to the diagrams.

Figure 6 is a schematic diagram illustrating the outline ofone embodiment ofthe cardiac pacing system. One ultra miniature integrated cardiac pacemaker (111) is implanted into the atrial endocardium ofthe patient. In Figure 6 as well as^in Figures 7 to ? 10 to be described below, H indicates the heart.

The cardiac pacing system in this embodiment is preferred in' cases where the atrium ' has lost the ability to keep pace although the electrical activity in the atrium and lhe electrical activity in the ventricle remain synchronized. For example, it may be. indicated : for patients with sick sinus syndrome in whom only sinus node function is impaired, while! intra-atrial conduction and atrio-ventricular conduction are preserved.

2q ThA »!fra miniature integrated cardiac pacemaker (111) implanted in the atrium is equipped with a control unit that outputs control signals, a heart stimulating means that responds to the control signals and electrically stimulates the atrial muscle, and an electrocardiographic information detecting means that detects the electrocardiographic information including at least intracardiac P wave information. It is designed such that the detected electrocardiographic information is output into the control unit. In other words, although the ultra miniature integrated cardiac pacemaker of the second embodiment of this invention is preferably used, the ultra miniature integrated cardiac pacemaker in accordance with the first, third and fourth embodiments can also be used as long as they possess the above-mentioned designs.

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Also, the control unit is equipped with a stimulation timing determining means that decides the timing of stimulation to generate control signals, and a stimulation timing changing means that changes the timing of stimulation to generate control signals.-

One example of operation of the cardiac pacing system in this embodiment will be explained below. By the stimulation timing determining means, control signals are generated according to a predetermined stimulation timing and the atrial ehdoqardiuip is stimulated electrically. This results in excitation and contraction of the atrial, myocardium, while at the same time this stimulus is conducted to the atrioventricular node through intra-atrial conduction pathway. Then, from the atrioventricular node, the stimulus is conducted to the His bundle, the left and right bundle branch, the Purkinje fiber and finally p,yciting the ventricular myocardium, resulting in a normal heart beat.

Even in sick sinus syndrome, a spontaneous heart beat may occur. If the electrocardiographic information detecting means detects spontaneous intracardiac P wave information within a given predetermined time from the prior heart beat, this spontaneous intracardiac P wave information is output into the control unit, meanwhile the timing of . stimulation to generate control signals is changed by the stimulation timing changing means of the control unit, and atrial pacing is suppressed. In case spontaneous intracardiac P wave information is not detected within a given time interval after the detection ot-prio-r intracardiac P wave information, the atrial myocardium will be stimulated electrically according to the predetermined stimulation timing.

By placing the above-mentioned ultra miniature integrated cardiac pacemaker in the ventricular endocardium of the patient, it is possible to stimulate the ventricular myocardium. By applying this pacemaker to patients who have normal sinus node function and only impaired atrioventricular conduction, it is possible to maintain the clinically required minimal number of ventricular contraction although there is no synchrony between the atrium and ventricle.

Next, a distributed cardiac pacing system according to another embodiment will be explained while referring to the diagrams.

24־2005-01

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Figure 7 is a schematic diagram mustrating .an outline of the distributed cardiac pacing system according to this embodiment. The schematic diagram shows one electrocardiographic information detecting device (200) in the atrial endocardium and one ultra miniature integrated cardiac pacemaker in accordance with this invention (131) in the 5 ventricular endocardium. Figure 8 is a block diagram illustrating the outline of the. electrocardiographic information detecting device (200).

The distributed cardiac pacing system in this embodiment is indicated: for patients who have normal sinus node function and whose atrioventricular conduction is^;only impaired. In detail, the electrocardiographic information detecting device (200) placed in 10 the atrial endocardium detects electrocardiographic information including at least spontaneous intracardiac P wave information. The detected electrocardiographic information including spontaneous intracardiac P wave information is transmitted to the ultra miniature integrated cardiac pacemaker (131) placed in the ventricular :endocardium. Upon receiving the electrocardiographic information of the spontaneous intracardiac P 15 wave information from the electrocardiographic information detecting device (200) and after a given lag (atrioventricular delay equivalent to the PQ interval in the ׳ electrocardiogram), the ultra miniature integrated cardiac pacemaker (131) conducts ventricular pacing by electrically stimulating the ventricular myocardium by the heart, stimulating means.

Even in patients with impaired atrioventricular conduction, spontaneous ventricular contraction may occur. In these patients, if ventricular contraction oc.curs (in case, of detection of spontaneous intracardiac QRS complex information) within a given time (atrioventricular delay) after the detection of spontaneous intracardiac P wave information, the stimulation timing is changed and ventricular pacing is not conducted.

Figure 8 is a block diagram illustrating the outline of the electrocardiographic information detection device (200) placed in the atrial endocardium. The ף / electrocardiographic information detection device (200) is composed of ari electrocardiographic information detecting means (5) that detects the electrocardiographic. ־ information including at least intracardiac P wave information and outputs the

&lt;־ע4''׳:143״1ץלדכלמ4-3 24 16:09 FROM־2005-01

TO 00101097236114101 P-70 electrocardiographic data, a transmitting means that sends electrocardiographic information (10), and a control unit (2),

In the electrocardiographic information detection device (200) shown in the diagram, the electrocardiographic information detecting means (5) is- composed of two 5 electrocardiographic information recording electrodes (53) that detect electrocardiographic information, an amplifying unit (51) that amplifies the electrocardiographic information (51), and an A/D conversion unit (52) that converts the electrocardiographic information into digital information.

Moreover, in the electrocardiographic information detection device (200) shown in 10 the diagram, the transmitting means (10) is composed of a modulating unit (11) that inputs and modulates the electrocardiographic information output from the control unit (2), and a transmitting unit (12) that sends the modulated electrocardiographic information by specified carrier wave. The modulated electrocardiographic information is sent to the ultra miniature integrated cardiac pacemaker (131) placed in the ventricular endocardium.

The ultra miniature integrated cardiac pacemaker (131) placed in the ventricle is composed of a control unit that outputs control signals, a heart stimulating means that responds to the control signal and electrically stimulates the ventricular myocardium, an electrocardiographic information detecting means that detects the electrocardiographic information including at least intracardiac QRS complexes, and a receiving means that receives and demodulates the electrocardiographic information sent from the electrocardiographic information detection device (200) placed in the atrium. It is. designed such that the electrocardiographic information detected by the electrocardiographic detecting means and the electrocardiographic information sent from elsewhere is input into the control unit. Therefore, in the distributed cardiac pacing system 25 of this embodiment, the ultra miniature integrated cardiac pacemakers of the fourth embodiment are preferably used as the ultra miniature integrated cardiac pacemakers placed in the ventricular endocardium, but the ultra miniature integrated cardiac pacemakers of the first embodiment can also be used without a problem.

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2005-0116:09 24־ FROM . ^;

Ftnftanno», the control unit la equipppdwith a Ki111ulatinn.t|ii1i>gftetatB1inF^. ^ ^: . .

meansthatdecidesthetimlngofstiniuladoniogeneratecontrolsignris.andasumulaiiori ׳

One example ofoperationofthe distributed cardiac pacing system in this : embodiment will be explained below. Usually, the ventricle is paced by the generation of control signals at a stimulation timing determined by the stimulation timing detemuiung. _d־vie־(pa־mgataa₅iv־ndm־ta^ intracardiac P wave information].

If spontaneous intracardiac QRS complex informarion is detected within a given time interval (atrioventricular delay) after the detection of intracardiac P wave inform ation, me thning of Stimnlation m generate conuol Signais is changed by the stimu^ changing means, and cnntrol signals are not generated.

-ח ultra mta^ iי ^״־ that the ventricle is paced rt regular intravpls lit» ⁸⁰®®®*⁶®י^W ' .

from the electrocardiographic information detection device (200) wrthm a given tune interval after intracardiac QRS complex information is detected (due to spontaneous ventricular contraction or due to stimulation by a cardiac pacemaker); This design wil assure safety if sinus arrest or sinoatrial block occurs.

Next, the distributed cardiac pacing system in another embodiment will be explained while referring to the diagram. Figure 9 is a schematic diagram illustrating a distributed cardiac pacing system according to this embodiment. The diagram shows a first ultra miniatureintegratedcardiaopa־emaker(101)placedintheatrialebiiocanhumanda second ultra miniature integrated cardiac pacemaker (102) placed in the ventricular endocardium.

׳Πιβ distributed cardiac pacing system in this embodiment may be indicated for patients with malfunction of the sinus node together with impaired atrioventricular conduction. In other words, this pacemaker is indicated for patients ,with sick sinus syndrome with manifestations of both arrest of sinus function and atrioventricular block.

200516:09 24־01־ FROM 43ץל7כלתH43b*4bzA TO 00101097236114101

One example of operation of the distributed cardiac pacing system in ±is embodiment will be explained. Ue first ultra miniature integrated cardiac pacemaker (101) placed in the atrial endocardium outputs control signals and paces the, atri urn by the heart stimulating means. This control signal (and/or electrocardiographic information of 5 atrium) is modulated into carrier waves and transmitted to the second ultra miniature integrated cardiac pacemaker (102) placed in the ventricular endocardium. Upon receiving the control signals (and/or electrocardiographic information of the atrium) from the first ultra miniature integrated cardiac pacemaker (101), the second ultra miniature integrated cardiac pacemaker (102) outputs control signals with a given delay (atrioventricular delay equivalent to the PQ interval on electrocardiogram) after the atrial pacing by the first ultra miniature integrated cardiac pacemaker (102), and electrically stimulates the ventricular myocardium to conduct ventricular pacing. Furthermore, this control signal (and/or electrocardiographic information of the ventricle) is modulated into a carrier wave and transmitted to the first ultra miniature integrated cardiac pacemaker (101). The first ultra miniature integrated cardiac pacemaker (101) suppresses detection of intracardiac P wave for a given time interval after receiving the control signal (and/or electrocardiographic information of the ventricle) from the second ultra miniature integrated cardiac pacemaker (102). Thereafter, the first ultra miniature integrated cardiac pacemaker (101) outputs control signals at a stimulation timing according to a predetermined fate, and stimulates the atrium.

By repeating the above, it is possible to pace the heart and mimic the natural physiological state.

Even patients with sick sinus syndrome with manifestations of both attest of sinus function and atrioventricular block may generate spontaneous ventricular contraction or 25 atrial contraction. If spontaneous intracardiac P wave information is detected within a given time from the prior heart beat, then the atrial pacing is suppressed. Moreover, if spontaneous intracardiac QRS complex information is detected within a .given time interval (atrioventricular delay) after the detection of intracardiac P wave information (spontaneous or due to the first ultra miniature integrated cardiac pacemaker), then 30 ventricular pacing is suppressed.

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P.73 endocardium is equipped wiih a control unit that outputs control signals, a heart Ί bating means that responds to the control signal and ־־־tH״־־y sta^the ־W myocardium, an electrocardiographic information detecting means that detects the electrocardiographic mfonnation including at least intracardiac ?wave information, a. transmitting means that modulates the control signal or electrocardiographic mformat«״־ end sends the information to the second ultra miniature integrated cardiac pacemaker (102) placed in the ventricle, and a receiving means that receives and demodulates the, control signal or electrocardiographic information sent from the second ultra mituature integrated cardiac pacemaker (102) placed in the ventricle. The pacemaker is designed such that the control signal and electrocardiographic infonnation sent from the second ultra miniature integrated cardiac pacemaker (102) are input into the control unit. :

Therefore, in the distributed cardiac pacing system of this embodiment (101), the ultra miniature integrated cardiac pacemaker of the first embodiment is preferably used as the 15 first ultra miniature integrated cardiac pacemaker (101).

The second ultra miniature integrated cardiac pacemaker (102) is equipped with[ a control unit that outputs control signals, a heart stimulating means that responds to the control signal and electrically stimulates the ventricular myocardium, an ;

electrocardiographic infonnation detecting means that detects the electrocardio^aphip 20 infonnation including at least intracardiac QRS complex information, a transmitting i means that modulates the control signal or electrocardiographic information and sends die information to the first ultra miniature integrated cardiac pacemaker (101), arid, a receiving means that receives and demodulates the control signal or electrocardiographic information sent by the first ultra miniature integrated cardiac pacemaker (101) placed in 25 the atrium. The pacemaker is designed such that the control signal and electrocardiographic information sent from the. first ultra miniature integrated cardiac: pacemaker (101) are input into the control unit. Therefore, in the distributed cardiac ! pacing system of this embodiment, the abovementioned ultra miniature integrated cardiac pacemaker of the first embodiment is preferably used as the second ultra miniature 30 integrated cardiac pacemaker (102).

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In the first ultra miniature integrated cardiac pacemaker (101), the control unit is equipped ־with a stimulation timing determining means that decides the. timing of stimulation to generate control signals, and a stimulation timing changing means that changes the timing of stimulation to generate control signals.

Usually, the stimulation timing determining means decides the timing of stimulation of control signal generation, and then generates control signals to conduct atrial pacing.

One example of operation of the first ultra miniature integrated cardiac pacemaker (101) will be explained. If the electrocardiographic information detecting means detects spontaneous intracardiac P wave within a given time from the prior heart beat, the timing of stimulation to generate control signals is changed, a control signal is not generated, and atrial pacing is not conducted. If the electrocardiographic information detecting means does not detect spontaneous intracardiac P wave information within a given time interval from the last heart bear, then a control signal is generated and atriaj pacing is conducted;

Moreover, in the control υηίζ if the control signal is generated or spontaneous intracardiac P wave information is detected, the information is sent from the transmitting. unit to the second ultra miniature integrated cardiac pacemaker (102).

In the second ultra miniature integrated cardiac pacemaker. (102), the control unit is equipped with a stimulation timing determining means that decides the timing of stimulation to generate control signals, and a stimulation timing changing mearis that changes the timing of stimulation to generate control signals.

One example of operation of the second ultra miniature integrated cardiac pacemaker (102) will be explained. Usually, a control signal is generated at a timing predetermined by the timing determining means [the control signal is generated; at a given time interval (atrioventricular delay) after the control signal or intracardiac P wave information is sent from the first ultra miniature integrated cardiac pacemaker (101)].

If spontaneous intracardiac QRS complex information is detected within a given time (atrioventricular delay), the timing of stimulation to generate control signals is changed by the stimulation timing changing means and ventricular pacing is not conducted.

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Moreover, in the control unit, if a control signal is generatedor spontaneous intracardiac QRS wave information is detected, the information is sent from the transmitting unit to the first ultra miniature integrated cardiac pacemaker (101). The first ultra miniature integrated cardiac pacemaker (101) suppresses the detection of intracardiac P wave information for a given time interval after receiving the control signal (or electrocardiographic information of the ventricle) from the second ultra miniature integrated cardiac pacemaker (102). This design is essential to prevent, the complication of so called pacemaker tachycardia caused by the following mechanism: when intracardiac QRS complex due to spontaneous ventricular contraction is conducted retrograde to the atrium, the first ultra miniature integrated cardiac pacemaker detects intracardiac P wave information, based on which the second ultra miniature integrated cardiac pacemaker electrically stimulates the ventricle, resulting in repeated electrical stimulation of the ventricle.

Next, a distributed cardiac pacing system in another embodiment will be explained while referring to the diagram. Figure 10 is a schematic diagram illustrating the distributed cardiac pacing system in this embodiment. The diagram shows an electrocardiographic information detecting device (200) placed in the atrial endocardium and multiple (for example, a total of 4 in Figure 10) ultra miniature integrated cardiac pacemakers (102) ' placed in the ventricular endocardium.

The distributed cardiac pacing system in this embodiment may be indicated for ! patients with impaired synchrony of ventricular myocardial contraction leading to lowered ventricular contractility, or patients at risk for fatal arrhythmia.

One example of operation of this distributed cardiac pacing system will be explained. The electrocardiographic information detecting device (200) placed in the atrial endocardium detects electrocardiographic information including at least intracardiac P wave information. The detected electrocardiographic information is sent to multiple ultra miniature integrated cardiac pacemakers (102) placed in the ventricular endocardium. Once electrocardiographic information is sent from the electrocardiographic information detecting device (200), multiple ultra miniature integrated cardiac pacemakers (102) generate control signals to stimulate the ventricular myocardium and pace the ventricle

TO 00101097236114101 P-76 */=7+3&lt;41?7כלו3+ 11 FROM־16 24־2005-01 with ־ delay after atrial contraction in time lag־ th״ vaty depending 0־ the individual ultra miniature integrated cardiac pacemakers (102). In ether, words, once electrocardiographic information is sent from the electrocardiographic information detecting device (200), the multiple ultra miniature integrated cardiac pacemakets (102) pace the ventricle after predetermined times depending on the ventricular sites at which the individual ultra miniature integrated cardiac pacemakers (102) are placed.

If spontaneous ventricular contraction occurs, that is, if spontaneous intracardiac. QRS complex information is detected within a given time interval (atrioventricular delay) after the detection of intracardiac P wave information, ventricular pacing is suppressed.

However, even though spontaneous intracardiac QRS complex information is detected, if the spontaneous beat is not detected within given time intervals at other multiple ultra miniature integrated cardiac pacemakers (102) placed in the ventricular endocardium, the ventricular pacing at these sites will not be suppressed. In order to realize this, spontaneous intracardiac QRS complex infonnation recoried by a pacemaker (102) at any 15 siteoftheventricleistransmittedtootherventricularpacemakers(102).Eachventricular pacemaker (102) mutually receives the signals sent from other ventricular pacemakers (102).

The ultra miniature integrated cardiac pacemaker (102) placed in the ventricular endocardium is equipped with a control unit that outputs control signals, a heart 20 stimulating means that responds to control signals and electrically stimulatestthc ventricular myocardium, an electrocardiographic infonnation detecting means tliat detects the electrocardiographic infonnation including at least intracardiac QRS complex information, a transmitting means that modulates the control signal or electrocardiographic information and sends the infonnation to other ultra miniature cardiac paceniakers placed 25 inthcventricle,andareceivingmeansthatreceivesanddemodulatescontr01:.signalB0r electrocardiographic information sent by the electrocardiographic information detecting device (200) placed in the atrium and other ultra miniature integrated cardiac paccmakets placed in the ventricle. Therefore, in this embodiment, the aforementioned ultra miniature integrated cardiac pacemakers ofthe first embodiment (100) are preferably used as the 30 ultra miniature integrated cardiac pacemakers (102).

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In addition, the sites where the ultra miniature integrated cardiac pacemakers arc to be placed and the number of the pacemakers wHl be set appropriately in accordance wi th the patient’s symptoms.

׳fhe control unit of each ultra miniature integrated cardiac pacemaker (102) is equipped with a stimulation timing determining means that decides the timing of stimulation to generate control signals, and a stimulation timing changing means that changes the timing of stimulation to generate control signals.

One example of operation of the ultra miniature integrated cardiac pacemaker wjU be explained. The stimulation timing determining means generates a control signal .at a predetermined stimulation timing [generates a control signal at a given time interval (atrioventricular delay) after spontaneous intracardiac P wave information is. transmitted from the electrocardiographic information detecting device (200)], and ventricular pacing is conducted.

The stimulation timing is different for each of the ultra miniature integrated cardiac pacemakers; in other words, it differs depending on the placement site of the pacemakers in the ventricular endocardium. For example, each ultra miniature integrated cardiac pacemaker (102) is stimulated with a time lag depending on when the site is stimulated in the normal ventricular beat But, the above-mentioned combination is not. restricted as long as it is a combination that maximally improves the contractility of the heart.

This kind of synchronized cardiac contraction also reduces the electrical instability of the ventricle, and is used to prevent arrhythmia in patients with a risk of fatal arrhythmia, and also to prevent pacemaker-indiiced arrhythmia.

The intracardiac QRS complex information detected by the ultra miniature integrated cardiac pacemaker (102) is transmitted to other ultra miniature integrated cardiac pacemakers via the transmitting means. If a certain ventricular pacemaker detects spontaneous intracardiac QRS complex within the predetermined time but this spontaneous beat is not detected at other ventricular pacemakers within given times, the above-mentioned design ensures that ventricular pacing also takes place in.these sites.

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24־2005-01

ע1-3ע b >לדכלו43 16:12 FROM

In th־ distributed cardiac pacing eystem, it is possible to place an 11IW miniature integrated cardiac pacemaker (101), instead of the electrocardiographic information detecting device (200), in the atrial endocardium just like the above-mentioned distributed cardiac pacing system in the previous embodiment. As described in the distributed cardiac 5 pacing system in the previous embodiment (i.e., the third embodiment of the distributed cardiac pacing system), the ultra miniature integrated cardiac pacemaker placed in the atria! endocardium is equipped with a stimulation timing determining means and stimulation timing changing means, and therefore may be used in patients with lowered: ventricular contractility accompanying sinus arrest and atrioventricular block, as well as in 10 patients with a risk of fatal arrhythmia accompanying sinus arrest and atrioventricular block.

In the distributed cardiac pacing system of this revised embodiment, .for the design of the ultra miniature integrated cardiac pacemaker placed in the atrial endocardium, one may adopt the design of the ultra miniature integrated cardiac pacemaker (101) placed in . 15 the atrial endocardium in the above-mentioned distributed cardiac pacing system in accordance with the previous embodiment (i.e., die third embodiment of the distributed cardiac pacing system). Furthermore, in the distributed cardiac pacing system m accordance with this revised embodiment, for the design of the ultra miniature integrated cardiac pacemaker placed in the ventricular endocardium, one may adopt the design of lhe 20 ultra miniature integrated cardiac pacemaker (102) placed in the ventricular endocardium in the above-mentioned distributed cardiac pacing system in this embodiment (i.e., the fourth embodiment of the distributed cardiac pacing system).

The ultra miniature integrated cardiac pacemaker in one embodiment transmits control signals or electrocardiographic information to other ultra miniature integrated 25 cardiac pacemakers and at the same time receives control signals or electrocardiographic information from other ultra miniature integrated cardiac pacemakers; thus it is able to pace the heart in synchrony with other ultra miniature integrated cardiac pacemakers.

The ultra miniature integrated cardiac pacemaker in another embodiment does not require lead wires to connect the pacemaker main body with the stimulation electrodes; 30 thus it is able to pace the heart without imposing extra burden on the patient.

TO 00101097235114101

P.79

24־2005-01

*24-sh״ F ץלק׳כלו(43 12 FROM .־ 16 '34

Th_eultraraimatureintegratedcardiacp־cen1akerinaT1otherembodimenttransrnits Mnmi ״ *״־״״»»״- ״^m ״ך דך ״י״ ״״יי ״ .

cardiac pacemakera; thus it is able to pace the heart in synchrony with other ultra miniature integrated cardiac pacemakers.

_s The ultra miniature integrated cardiac pacemaker in yet anolher embodiment .

_receives control signals or electrocardiographic information from other ultra miniature _tot־grat־d־־rdi־־p־״־־־k־re;^ ultra miniature integrated cardiac pacemakers.

The distributed cardiac pacemaker system in another embodiment can be used for 10 pacing in patients whose atrium has lost the ability to keep pace although the electnca!

activity in the atrium and the electrical activity in the ventricle remain synchronized.

The distributed cardiac pacemaker system in still another embodiment can be used in patients With normal sinus node fimetion but in whom atrioventricular, eonducl»״ is only impaired.

₁₅ The distributed cardiac pacemaker system in another embodiment era be used m patients whose sinus node is not functioning normally and atrioventricular conduction ,s ' also impaired.

The distributed cardiac pacemaker system in yet another embodiment can be used m patients who have lost synchrony of contraction among various parts ofthe ventnele 20 together with lowered ventricular contractility, or patients with arrhythmia.

The distributed cardiac pacemaker system ih another embodiment can be used in patients with lowered ventricular contractility accompanying sinus arrest and atrioventricular block, as weU as patients with a risk of fetal arrhythmia accompanying sinus arrest and atrioventricular block.

The present invention provides an ultra miniature integrated cardiac pacemaker and distributed cardiac pacing system which allow pacing of the heart without the need for. the conventional lead wires that connect the electrodes with the pacemaker maid body, and

200516:13 24־01־ FROM 49־*

TO 00101097236114101 P-80 allow implantation in the heart by catheter manipulation only without incision of the chestwall to reduce burden on the patient.

Accordingly, it is to be understood that the embodiments of the invention heraii described are merely illustrative of the application of the principles of the invention.

Reference herein to details of the illustrated embodiments is not intended to lifhit the scope of the claims, which themselves recite those features regarded as essential to the invention.