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Publication numberUS3650277 A
Publication typeGrant
Publication dateMar 21, 1972
Filing dateFeb 17, 1970
Priority dateFeb 24, 1969
Also published asDE2008316A1
Publication numberUS 3650277 A, US 3650277A, US-A-3650277, US3650277 A, US3650277A
InventorsUlf Hakan Sjostrand, Per Ake Oberg
Original AssigneeLkb Medical Ab
Export CitationBiBTeX, EndNote, RefMan
External Links: USPTO, USPTO Assignment, Espacenet
Apparatus for influencing the systemic blood pressure in a patient by carotid sinus nerve stimulation
US 3650277 A
Abstract
A system for reducing and controlling the blood pressure of a hypertensive patient has electrical pulse stimulation of the carotid-sinus nerves controlled by the arterial blood pressure of the patient in such a manner that the number of stimulation pulses within each heart cycle is determined by the arterial means blood pressure whereas the distribution of stimulation pulses over the heart cycle is a function of the arterial pulse wave shape with the pulse frequency being greater during the first portion of the heart cycle.
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Description  (OCR text may contain errors)

United States Patent Sjostrand et al.

[ Mar. 21, 1972 APPARATUS FOR INFLUENCING THE SYSTEMIC BLOOD PRESSURE IN A PATIENT BY CAROTID SINUS NERVE STIMULATION Ulf Hakan Sjostrand, Uppsala', Per Alte Oberg, Brunna, both of Sweden LKB Medical AB, Bromma, Sweden Feb. 17, 1970 Inventors:

Assignee:

Filed:

Appl. No.:

Foreign Application Priority Data Feb. 4, 1969 Sweden ..2528/69 U.S. Cl. ..l28/419 C, 128/421 Int. Cl. ..A6ln l/36 Field of Search ..128/418,419 R, 421,422,423,

128/205 A, 2.05 P, 2.05 E, 2.05 M, 2.05 B, 2.05 R, 206 A, 2.06 R, 2.1 B, 2.1 R

blood pressure Arterial 8 Pressu're transducer 0 Q Mean value circuit Differeutiating circuit [56] References Cited UNITED STATES PATENTS 3,358,690 12/1967 Cohen 128/419 R 3,199,508 8/1965 Roth ....128/2.06 R 3,421,511 1/1969 Schwartz et al ..128l418 OTHER PUBLICATIONS Bilgutay et al., Transactions of American Society of Artificial lntemal Organs, Vol. X, 1964, pp. 387- 393 Primary Examiner-William E. Kamm Attorney-Zabel, Baker, York and Jones [57] ABSTRACT A system for reducing and controlling the blood pressure of a hypertensive patient has electrical pulse stimulation of the carotid-sinus nerves controlled by the arterial blood pressure of the patient in such a manner that the number of stimulation pulses within each heart cycle is determined by the arterial means blood pressure whereas the distribution of stimulation pulses over the heart cycle is a function of the arterial pulse wave shape with the pulse frequency being greater during the first portion of the heart cycle.

6 Claims, 6 Drawing Figures PATENTEDMARZI m2 3.650.277

SHEET 1 [IF 3 Fig.1 P

Arteriof Vusomotor blood 5 pressure umreceptors centers Effector systems Arterial blood- 8 Flg 2 pressure Left sinus nerve Right sinus nerve APPARATUS FOR INFLUENCING THE SYSTEMIC BLOOD PRESSURE IN A PATIENT BY CAROTID SINUS NERVE STIMULATION The present invention is related to an apparatus for influencing the systemic blood pressure in human beings and more particularly for reducing and controlling the blood pressure in hypertensive patients.

The blood pressure regulatory system of higher mammals and man is preferably described and studied as a closed-loop control system. FIG. 1 in the enclosed drawing illustrates a lay-out of this control system. The arterial systemic blood pressure is sensed by baroreceptors 2 in the body, which can be regarded as pressure-signal-transducers to convey information on the actual arterial blood pressure through afferent nerve paths to the vasomotor center 3. Man has several such baroreceptor areas, the most important ones being located at the aorta arch and in the two carotid-sinus regions. As components in a closed-loop control system these baroreceptors may be regarded as parameter sensors conveying information to the vasomotor center of the actual arterial blood pressure. With reference to a closed-loop control system, the vasomotor center can be regarded as a comparator and regulator which compares the information about the actual blood pressure received from the baroreceptors with information about the desired blood pressure received from other cardio-vascular centers and other receptors in the body and which in response to this comparison influences those effector systems 4 in the body directly determining the systemic arterial blood pressure. These effectors are primarily the heart, the volume rate of which is an important factor determining the systemic blood pressure, and the peripheral-vascular system, in particular the arterial system but also the venous system, the contraction and dilation of which affect the blood pressure. For the treatment of hypertensive patients one uses at the present in most cases various types of drugs which either affect the effectors, primarily the peripheral-vascular system for reduction of the blood volume, or have an inhibiting effect upon the nerve activity from the vasomotor center to the effectors. These drugs have, however, the very serious disadvantage that they impair considerably the capacity of the natural biological blood pressure regulatory system for producing the natural and desired adjustment of the blood pressure to the activity of the patient and other factors, which would normally cause changes in the blood pressure.

Therefore one has in the last years become interested in the possibility of influencing the blood pressure through the nerve activity on the afferent nerve paths from the baroreceptors to the vasomotor center by artificial stimulation of these nerves by means of electric pulses so that the natural nerve activity is supplemented or replaced with an artificially increased nerve activity, in response to which the vasomotor center is caused to reduce the blood pressure. In this way it is possible to obtain a reduced pressure level while maintaining the biological blood pressure regulatory system unaffected so that this can provide a natural control of the blood pressure at the reduced level. This method should of course be particularly advantageous in those cases where the hypertension is caused by an abnormally low sensitivity of the baroreceptors so that for a given arterial blood pressure the baroreceptors produce a substantially lower nerve activity than would be the case in a normotensive patient. Nerves suitable for such an electrical stimulation are primarily the sinus nerves from the baroreceptors in the two carotid-sinus areas, as these nerves are comparatively easily accessible. Experiments carried out with electrical stimulation of the sinus nerves or the carotid-sinus areas with electric pulse series have also verified that such a stimulation has a certain reducing effect on the blood pressure. However, the practical results obtained have been comparatively limited, which seems primarily to have been due to the fact that the artificial electrical stimulation has not been sufficiently similar to the natural nerve activity from the baroreceptors, wherefore the vasomotor center has not responded to the artificially stimulated nerve activity in the intended manner.

The object of the present invention is therefore to provide an improved apparatus for influencing the blood pressure in a patient, in particular for reducing the blood pressure of a hypertensive patient, by electrical stimulation of afferent nerve paths from the baroreceptors of the patient, in particular the sinus nerves from the carotid-sinus areas. The device according to the invention comprises as already suggested in the prior art an electrode or stimulator assembly which can be applied on or close to an afferent nerve for stimulation thereof with short electric pulses and a pulse generator connected to said stimulator assembly for supplying stimulating pulses thereto. Preferably one uses two electrode or stimulator assemblies to be applied to each one of the sinus nerves of the patients in which case the pulse generator is provided with two pulse outputs connected to said two stimulator assemblies respectively. The device according to the invention is characterized in that it comprises a signal generator for producing a control signal for the pulse generator dependent on the. heart activity of the patient and that the pulse generator produces in response to said control signal during each heart cycle a pulse series of limited length, which starts at the beginning of the heart cycle and in which the majority of pulses appear during the first portion of the heart cycle.

The device according to the invention satisfies two essential conditions for a true-to-nature stimulation of the afferent nerve activity on the sinus nerves, namely on the one hand that the stimulation is synchronized to the heart activity of the patient and consists of a limited pulse series during each heart cycle and on the other hand that this pulse series has the majority of its pulses concentrated to the first portion of the heart cycle.

in a more refined embodiment of the invention, the signal generator responsive to the heart activity of the patient may consist of a pressure transducer which is connected to an artery of the patient and produces an electric output signal substantially representing the instantaneous arterial blood pressure of the patient. Such a pressure transducer may for instance consist of a strain gauge device coupled to the artery through a catheter inserted therein. It is also possible to mount the pressure transducer externally on the artery so as to be affected by the stresses in the wall of the vessel, which stresses are dependent on the blood pressure in the vessel. It is of course also possible to use other types of pressure sensitive electrical transducers, as for instance piezoelectric crystals. The electric output signal which is obtained from the pressure transducer and which varies with the instantaneous arterial blood pressure of the patient is supplied to signal transforming circuits which produce a first signal representative of the arterial mean blood pressure of the patient and a second signal representative of the derivative or rate of change of the arterial blood pressure of the patient and which sum said first and second signals and produces a signal corresponding to said sum, said last-mentioned signal being connected to the pulse generator as a control signal therefor and the pulse generator being adapted to produce pulses having a pulse frequency corresponding to the amplitude of the control signal supplied to the generator. Thus, also in this embodiment of the invention a stimulation is obtained which is synchronized with the heart activity of the patient in that a limited pulse series is produced during each arterial pulse cycle so as to start at the beginning of the pulse cycle. However, each such pulse series will contain a number of pulses determined by the prevailing arterial means blood pressure and display a pulse frequency modulation determined by the shape of the arterial pulse wave during the current pulse cycle. As the arterial pulse wave has a large positive derivative of comparatively short duration at the beginning of the pulse cycle and thereafter during the remaining, substantially longer portion of the pulse cycle a smaller negative derivative, each pulse series will display a pulse frequency which after an initial and rapid increase in pulse frequency decreases continuously from its maximum value at the beginning of the pulse series. With such a design of the device according to the invention the artificially stimulated nerve activity will duplicate the natural biological nerve activity from the baroreceptors with a much higher fidelity. As, furthermore, the artificial stimulation of the nerve activity is dependent on the mean blood pressure of the patient as well as the derivative of the blood pressure, that is the shape of the arterial pulse wave, the device according to the invention will form an integral part of the natural biological blood pressure regulator system. Related to this regulator system the device. according to the invention can be regarded as a parameter sensor which supplements the natural biological parameter sensors in the blood pressure regulatory system formed by the baroreceptors of the patient.

In the following the invention will be further described with reference to the accompanying drawing, in which HO. 1 is the schematic and very simplified block diagram described in the foregoing for the natural biological blood pressure regulator system;

FIG. 2 shows by way of example the block diagram for an embodiment of a device according to the invention, in which the artificial stimulation of the nerve activity is dependent on the arterial mean blood pressure as well as the derivative of the arterial blood pressure;

FIG. 3 is a diagram schematically illustrating the natural afferent nerve activity from a baroreceptor during an arterial pulse cycle for different arterial mean blood pressures;

FIG. 4 is a diagram of the mean pulse frequency of the stimulating pulses as a function of the mean pressure for the device according to the invention illustrated in FIG. 2;

H6. 5 is a diagram illustrating schematically the pulse series produced by the device according to the invention illustrated in FIG. 2 for a sinusoidally varying pressure and for different settings of the device; and

FIG. 6 shows a number of blood pressure curves illustrating the blood pressure regulation obtained in experiments on dogs with a device according to FIG. 2 as compared with the blood pressure regulation caused by the natural baroreceptors in the carotid-sinus areas.

In FIG. 3 curve A illustrates schematically the shape of the normal arterial pulse wave during an arterial pulse cycle, whereas curve B illustrates the corresponding ECG-signal. The diagrams C, D, E, F and G respectively illustrate the nature of the afferent nerve activity on the sinus nerve during the heart pulse cycle for different arterial mean blood pressures. As illustrated by these diagrams this nerve activity consists of pulse series. A characteristic property of this nerve activity is that it is synchronized with the arterial pulse cycle so that the nerve activity consists of a pulse series for each arterial pulse cycle starting at the beginning of the arterial pulse cycle and having its pulses primarily concentrated in the first portion of the arterial pulse cycle. The number of pulses in each pulse series, that is the mean pulse frequency of the pulse series, is dependent on the arterial mean blood pressure in such a manner that the number of pulses increases with increasing arterial mean blood pressure. There is a lower threshold level at about 40-50 mm. Hg. below which no nerve activity exists and an upper saturation level at about 200-250 mm. Hg. above which the nerve activity is saturated and each pulse series comprises a maximum number of pulses which is not additionally increased for increasing arterial means blood pressure. Another characteristic property of the afferent pressure responsive nerve activity is that each pulse series is modulated with respect to its pulse frequency, generally speaking in such a manner that the pulse frequency decreases continuously during the duration of the pulse series from a maximum frequency at the beginning of the pulse series.

In a device according to the invention for electrical stimulation of the afferent nerve activity for instance on the sinus nerve, in order to influence the blood pressure the aim must consequently be to compose this stimulation in such a manner that it copies or resembles as closely as possible the natural nerve activity illustrated in FIG. 3 and described above.

For this purpose the device according to the invention may in the most simple case comprise a pulse generator having a pulse output connected to a stimulator or electrode assembly applied on or close to a selected nerve or nerves and designed to produce in response to a starting signal a pulse series having a predetermined number of pulses and a predetermined pulse frequency. For the synchronization of the pulse generator and thus the nerve stimulation with the heart cycle of the patient one may preferably use an electrode located at or close to the heart of the patient for picking up an ECG-signal which is supplied to the pulse generator as a control signal therefor, in which case the pulse generator is designed to start a pulse series in response to the readily detectable R-wave in the ECG- signal at the beginning of each a heart cycle. By adjustment of the length, the pulse frequency and possibly also the'pulse frequency modulation of the pulse series produced by the pulse generator to the natural biological regulatory response of the patient in question it is possible to achieve a desired reduction of the blood pressure level of the patient. However, it is appreciated that in such a simple device according to the invention the artificial stimulation of the nerve activity will not adapt itself automatically to the prevailing arterial mean blood pressure of the patient as the natural nerve activity does (F IG. 3) and neither will it be affected by any variations in the shape of the arterial pulse wave. Although such a simple device has produced good results in experiments that have been made, it is more advantageous to make also the artificial stimulation on the nerve activity dependent of the arterial mean blood pressure on the patient and also of the shape of the arterial pulse wave.

FIG. 2 illustrates the fundamental block diagram for such a more sophisticated device according to the invention. This device includes two identical electrode or stimulator assemblies 5 and 6 adapted to be applied on or close to the sinus nerves of the patient for electrical stimulation of the nerve activity therein. Each such stimulator or electrode assembly may for instance include two loop-shaped electrodes arranged to enclose the nerve at spaced positions. Also other types and locations of the stimulator assemblies may of course be used. The two stimulator assemblies 5 and 6 are connected to separate pulse outputs from a controlled pulse generator 7 of any suitable design, which on its two outputs produces pulses having a pulse frequency determined by a control signal, as for instance a direct voltage signal, applied to the control input of the pulse generator. Consequently the two stimulators 5 and 6 are supplied with identical pulse series from the pulse generator 7. However, the one output of the pulse generator is provided with a delay circuit 15 so that the pulse series on this output is delayed relative to the pulse series on the other output by a delay time which is shorter than the shortest interval between two successive pulses in the pulse series. In this way cross-stimulation between the two stimulators 5 and 6, that is between the left side and the right side of the patient, is prevented. The device includes also a pressure transducer 8 of suitable type, which can be connected or applied to an artery of the patient and which produces an electric output signal which is substantially proportional to the instantaneous arterial blood pressure of the patient. As mentioned in the foregoing, such a pressure sensitive signal transducer may consist of a strain gauge transducer which is connected to the artery through a catheter inserted into the artery or is mounted externally on the artery so as to be affected by the mechanical stresses in the wall of the artery.

The output signal from the pressure transducer 8, representing the instantaneous arterial blood pressure, is through an amplifier 9 supplied to two signal transforming circuits l0 and 11. The circuit 10 is designed to calculate on the basis of the input signal the arterial mean blood pressure and to produce an output signal proportional thereto. The calculation of the arterial mean blood pressure may be carried out in various manners. For instance the circuit 10 may consists of a mean value rectifying circuit having a suitable time constant. In a practical device according to the invention, however, the circuit 10 includes two peak detecting amplifiers which are connected to the signal from the pressure transducer 8 with opposite polarities so that the one amplifier produces an output signal representing the systolic blood pressure, whereas the other amplifier produces an output signal representing the diastolic blood pressure. These two output signals are supplied to an analog summing circuit which sums the two signals according to the equation menn dlnalollc fi auatollc dlaslollc) This is an approximative expression for the arterial mean blood pressure P based upon a substitution of a triangular curve for the arterial pulse wave. The output signal from the circuit 10, proportional to the calculated arterial mean blood pressure, is connected through a variable circuit element 12, as for instance a potentiometer, to the one input ofa signal adding amplifier 13. By means ofahe potentiometer 12 it is possible to vary the proportionality factor for the signal representing the mean blood pressure.

The second signal transforming circuit 11 is a differentiating circuit which produces an output signal having an amplitude proportional to the derivative or rate of change of the arterial blood pressure and a polarity corresponding to the sign of this derivative. The output signal from the differentiating circuit 1] is supplied through a variable circuit element 14, for instance a potentiometer, to the second input of the signal adding amplifier 13. By means of the potentiometer 14 it is consequently possible to vary the proportionality factor for the signal from the differentiating circuit 11 representating the derivative of the blood pressure. The signal adding amplifier I3 sums the two input signals and produces an output signal proportional to the sum. This output signal is connected to the pulse generator 7 as a control signal therefor. Consequently the pulse generator will generate pulses having a frequency proportional to the sum of the prevailing arterial mean blood pressure, as calculated by the circuit 10, and the instantaneous derivative of the arterial blood pressure, as determined by the circuit 11. However, the pulse generator 7 is designed to have a lower threshold level for the input signal below which threshold value no pulses are generated. This lower threshold level for the input signal corresponds preferably to a constant non-varying blood pressure of about 40-50 mm. Hg. Further the pulse generator has preferably an upper saturation frequency of for instance about 300 Hz., which is reached for an input signal corresponding to a constant non-varying blood pressure of for instance about 250-300 mm. Hg. It is appreciated that the pulse series generated by the pulse generator 7 will have a mean pulse frequency determined by the magnitude of the calculated arterial mean blood pressure and the setting of the potentiometer l2 and a pulse frequency modulation determined by the derivative of the arterial blood pressure, that is the shape of the arterial pulse wave, and the setting of the potentiometer 14.

FIG. 4 is a diagram illustrating the relationship between the mean pulse frequency of the pulse series produced by the pulse generator 7 and the mean pressure sensed by the pressure transducer 8 for a pressure which varies sinusoidally about the mean pressure with the frequency 2 Hz. This relationship is substantially linear and substantially independent of the setting of the potentiometer 14, that is of the magnitude of the component of the control signal for the pulse generator 7 corresponding to the derivative of the pressure. This is also what one would expect, as for a signal varying periodically about a constant value, the time integral of the positive derivative of the signal is always equal to the time integral of the negative derivative of the signal.

In FIG. 5 the diagrams H, J and K illustrate the pulse series produced by the pulse generator 7 for different settings of the potentiometer 14, when the pressure transducer 8 is affected by a pressure which varies sinusoidally about a given mean pressure with the frequency 2 Hz. as illustrated by the curve L. The pulse series illustrated by the diagram H is obtained when the potentiometer 14 has such a setting that the signal supplied to the signal adding amplifier 13 from the differentiating circuit 11 is zero, that is when the pulse generator 7 is controlled only by the signal representing the mean pressure from the circuit 10. As expected one obtains in this case a constant pulse frequency, the magnitude of which is determined by the mean pressure. The diagrams J and K respectively illustrate pulse series obtained when the potentiometer 14 has such a setting that a certain signal proportional to the derivative of the pressure is supplied from the circuit 11 to the adder amplifier 13, this derivative representing signal component being larger in the case illustrated by the curve K than in the case illustrated by the diagram J. As can be seen these two pulse series contain substantially the same number of pulses during each period of the varying pressure (curve L), whereas the pulses are distributed differentially over the period dependent on the relative magnitude of the derivative representing signal component from the circuit 11.

Experiments have been carried out on animals in order to compare on the one hand the blood pressure reducing and regulating effects that can be obtained by artificial stimulation of the nerve activity in the sinus nerves by means of a device according to the invention designed as illustrated in FIG. 2 as against the natural blood pressure regulating effect caused by the natural afferent nerve activity on the sinus nerves in response to the baroreceptors in the carotid-sinus areas. For these experiments dogs have been used, as the vascular system in dogs is very similar to that in man and as anesthetic techniques are developed for dogs which do not give cause to any disturbance in the blood pressure regularoty system.

The experiments were carried out in the following manner: The two carotid-sinus regions of the animal were dissected free. The common carotid artery on each side was provided with a device by means of which the artery could be clamped for a desired time interval and thereafter reopened. On each side of a catheter was inserted into the carotid-sinus and fixed by a ligature as close as possible to the bifurcation between the external and the internal carotid arteries. These two catheters were connected through polyethene catheters and a valve to a catheter inserted into the femoral vein. By means of the valve it was possible to open or close the communication between the two sinuses and the femoral vein. By clamping the two common carotid arteries and simultaneously opening the c0mmunication between the two sinuses and the femoral vein it was possible to produce such a low and pulsation-free blood pressure in the sinuses that the normal nerve activity from the baroreceptors in the two carotid-sinus areas was completely interrupted. Consequently, this corresponded to a complete disconnection of the natural baroreceptors from the natural biological blood pressure regulatory system of the experimental animal.

The sinus nerves from the carotid-sinus areas were also dissected free and on these nerves the two stimulators 5 and 6 of the device according to the invention (FIG. 2) were applied near to the origin of the nerves in the sinuses. The pressure transducer 8 of the device according to the invention (FIG. 2) was connected to a catheter inserted in the femoral artery. The output signal from the pressure transducer 8 was connected not only to the two signal transforming circuits l0 and 11 in the device according to the invention but also to a recorder for recording the arterial blood pressure of the animal during the experiment.

At the experiments the two common carotid arteries were clamped at the same time as the two sinuses were connected to the femoral vein through the catheters inserted in the sinuses and the valve device. This caused a pronounced rise in the arterial blood pressure of the experimental animal, which was exactly what could be expected, as the normal nerve activity from the baroreceptors in the two carotid-sinus areas was interrupted, as explained in the foregoing. This state was maintained until it was certain that a stable arterial blood pressure (at the higher level) had been obtained. Thereafter the two common carotid arteries were reopened instantaneously and at the same time the communication between the catheters inserted in the sinuses and the femoral vein respectively was interrupted. In this way a very rapid transient rise in the intrasinusal blood pressure was produced and thus a stepfunction activation of the baroreceptors in the carotid-sinus areas. The arterial blood pressure of the experimental animal returned then to its original value under the influence of the reappearing normal afferent nerve activity in the sinus nerves from the baroreceptors. This natural regulatory response of the natural biological blood pressure regulatory system under the influence of the operation of the natural baroreceptors was studied by means of the recording of the arterial blood pressure of the animal made by the recorder. The curve M in FIG. 6 illustrates the typical variation of the systolic pressure of an experimental animal during such an experimenL The experiments showed that the variations in the systolic pressure and the diastolic pressure respectively were so similar that it was only necessary to record one of them. In the experiment corresponding to curve M in FIG. 6 the common carotid arteries were clamped at the time T and reopened at the time T As can be seen, a well damped regulatory response is obtained on the momentary stepwise rise in the intrasinusal pressure and the systemic blood pressure is returned comparatively rapidly to a constant value equal to the value before the experiment, which shows also that the natural biological blood pressure regulatory system has not been permanently affected by the experiment.

The experiment described above was thereafter repeated but with the difference that at the time T the common carotid arteries were not opened and neither was the communication between the catheters inserted in the sinuses and the femoral vein respectively interrupted. Consequently the natural baroreceptors in the two carotid-sinus areas remain inoperative. Instead at the time T an artificial stimulation of the sinus nerves was started by means of the device according to the invention (FIG. 2). The curves N, O and P in FIG. 6 illustrate typical regulatory responses in the systolic pressure of the experimental animal under the influence of such an electric stimulation of the sinus nerves for different settings of the potentiometer 14 in the device (FIG. 2), that is for different magnitudes of the control signal component of the pulse generator dependent on the derivative of the blood pressure. At the experiment illustrated by curve N the potentiometer 14 had such a setting that no signal component from the circuit 1] dependent on the derivative of the blood pressure was sup plied to the adder amplifier l3 and thus to the pulse generator 7. Consequently, in this case the stimulation was carried out with a constant pulse frequency during the entire cardial cycle, the magnitude of this pulse frequency being determined by the arterial mean blood pressure of the animal. As can be seen this artificial stimulation of the sinus nerves caused the blood pressure to return to a level substantially equal to the value before the clamping of the carotid arteries. However, the blood pressure returned to its original value through very pronounced oscillations, remaining for a considerable time, and the regulatory response has consequently in this case a very low damping.

In the experiment illustrated by curve the potentiometer 14 had such a setting that a certain but comparatively small signal component representing the derivative of the blood pressure was supplied to the pulse generator 7. In this case a considerably more damped response was obtained, but still the amplitude and the duration of the oscillations were considerably larger than in the natural biological regulatory response illustrated by curve M.

In the experiment illustrated by curve P the potentiometer 14 had such a setting that a substantially larger signal component representative of the derivative of the blood pressure was supplied to the pulse generator than in the experiment illustrated by curve 0. As can be seen, in this case a well damped regulatory response was obtained which was very similar to the natural biological regulatory response illustrated by curve M.

Consequently, the experiments show that it is essential that the artificial stimulation of the afferent nerve activity has a pulse frequency which is modulated in such a way, preferably in dependence of the derivative of the arterial blood pressure,

that the majority of the stimulation pulses appear during the first portion of the hear cycle, if a regulatory response is to be achieved which is similar to the natural regulatory response caused by the natural nerve activity from the baroreceptors.

Between the different experiments which artificial stimulation of the nerve activity with a device according to the invention the natural regulatory response was checked repeatedly in that the clamping of the carotid arteries was removed as described above in connection with curve M in FIG. 6. The purpose of this was to check that the artificial stimulation of the sinus nerves did not have any permanently remaining effect upon the natural blood pressure regulatory system. No such remaining changes could be found.

As it is known that the biological baroreceptors have different sensitivities for the positive and the negative derivative of the blood pressure respectively, experiments have also been made with a device according to the invention as shown in FIG. 2, in which, however, the differentiating circuit 11 was so designed that it could be set to have unequally large amplifications for the positive derivative and the negative derivative respectively. Comparative experiments were made on the one hand with unequally large amplifications for the positive and the negative derivatives and on the other hand with equally large amplification for both derivatives. The regulatory responses obtained at these experiments did not, however, shown any marked fundamental differences. Just as described in the foregoing, however, it was observed that a large signal component dependent on the derivative of the blood pressure supplied to the pulse generator 7 produces a more damped response than a small signal component dependent on the derivative. Further experiments have shown that a relatively large signal component, dependent on the mean blood pressure from the circuit 10 (set by means of the potentiometer 12) to the pulse generator 7, i.e., a higher mean pulse frequency for the stimulation, gives a lower blood pressure level than a smaller static signal component from the circuit 10 to the pulse generator 7, i.e., a lower mean pulse frequency for the stimulation.

It is appreciated that in the practical use of a device according to the invention it may be necessary to adjust the relative magnitude of the mean pulse frequency of the stimulation, which is dependent on the arterial mean blood pressure of the patient, and the pulse frequency modulation which is dependent on the blood pressure derivative of the patient as well as to adjust the lower threshold level for the pulse generation and the maximum saturation pulse frequencyrespectively to the patient concerned if optimum results are to be obtained.

In the experiments on dogs the stimulation was made with square wave pulses having an amplitude of 2 v. and a pulse length of 0.1 msec. However, it is appreciated that the pulse amplitude as well as the pulse length must be adjusted to the actual design of the stimulator assemblies and their location relative to the nerves to be stimulated so that the desired nerve activity is achieved in the nerves. However, it seems that a pulse amplitude within the range l-5 v. and a pulse length within the range 0.1-2 msec. should be suitable.

In a device according to the invention the two stimulator assemblies and the pressure transducer sensing the arterial blood pressure may be permanently implanted in the body and connected through wire conductors to a unit located outside the said external unit including the pulse generator, the signal transforming circuits and the necessary power source. Alternatively the stimulator assemblies and the pressure transducer may be coupled inductively to said external unit. It is also possible to miniaturize the device so that the complete device can be subcutaneously implanted, in which case it is preferably provided with inductively rechargeable batteries so that the device does not have to be removed for replacement of the batteries.

What is claimed is:

l. A system for influencing the natural biological blood pressure regulatory system in an individual, in particular for reducing and controlling the blood pressure in a hypertensive individual, by electrical pulse stimulation of an afferent nerve from a baroreceptor in the individual, said system comprising:

1. pressure sensitive transducer means adapted to be connected to the arterial system of the individual for sensing the arterial blood pressure and producing an electric output signal substantially representing the instantaneous arterial blood pressure in the individual;

. signal transforming means receiving the transducer output signal and including (a) a first signal transforming circuit providing an output signal substantially proportional to the mean value of the transducer output signal, and (b) a second signal transforming circuit providing an output signal whose amplitude is proportional to the derivative of the transducer output signal and whose polarity corresponds to the algebraic sign of said derivative;

3. signal combining means for additively combining the output signals of said first and second signal transforming circuits and providing an output signal whose amplitude is a function of said combined signals;

4. a frequency controlled pulse generator receiving the output signal of said signal combining means as a frequency control signal for generating output pulses having a frequency proportional to the amplitude of the output signal of said signal combining means; and

. stimulator means connecting to receive the output pulses of said pulse generator and including at least one electrode means adapted for connection to an afferent nerve from a baroreceptor in the individual.

2. A system according to claim 1, wherein said pulse generator has a minimum threshold signal value for its frequency control signal to initiate operation of the generator.

3. A system according to claim 1, comprising variable signal attenuating means connected between the outputs of said first and second signal transforming circuits and the input of said signal combining means for variation of the relative magnitudes of the signals combined by said signal combining means.

4. A system according to claim 1, wherein said second signal transforming circuit has unequally large proportionality factors for the positive and negative derivatives respectively of the transducer output signal.

5. A system according to claim 1, wherein said pulse generator has a pulse frequency range up to about 300 Hz.

6. A system for influencing the natural biological blood pressure regulatory system in an individual, in particular for reducing and controlling the blood pressure in a hypertensive individual, by electric pulse stimulation of an afferent nerve from a baroreceptor in the individual, said system comprising:

1. pressure responsive transducer means adapted to be connected to the arterial system in the individual for sensing the arterial blood pressure and producing an output signal substantially representing the instantaneous arterial blood pressure in the individual;

2. signal transforming means responsive to the transducer output signal and including (a) a first signal transforming circuit providing an output signal substantially proportional to the mean value of the transducer output signal, and (b) a second signal transforming circuit providing an output signal whose amplitude is substantially proportional to the derivative of the transducer output signal and whose polarity corresponds to the algebraic sign of said derivative;

3. signal combining means for additively combining the output signals of said first and second signal transforming circuits to provide an output signal whose amplitude is a function of said combined signals;

4. a frequency controlled pulse generator connected to receive the output signal of said signal combining means as a frequency control signal to generate output pulses having a pulse frequency proportional to the amplitude of the output signal of said signal combining means; said pulse enerator having two out uts for said output pulses; 5. stimu ator means including rig t and left electrode means connected to receive the output pulses from the two outputs respectively of the pulse generator and adapted for connection to the right and left carotid-sinus nerves respectively in the individual; and 6. a pulse delay circuit in the one generator output connection for providing a time delay shorter than the shortest interval between two successive output pulses from the generator to prevent cross-stimulation between the right and left carotid-sinus nerves in the individual.

* IIK

Patent Citations
Cited PatentFiling datePublication dateApplicantTitle
US3199508 *Apr 25, 1962Aug 10, 1965W R Medical Electronies CoCoding of physiological signals
US3358690 *Nov 18, 1964Dec 19, 1967Cohen Marvin MHeart stimulator utilizing a pressuresensitive semiconductor
US3421511 *Dec 10, 1965Jan 14, 1969Medtronic IncImplantable electrode for nerve stimulation
Non-Patent Citations
Reference
1 *Bilgutay et al., Transactions of American Society of Artificial Internal Organs, Vol. X, 1964, pp. 387 393
Referenced by
Citing PatentFiling datePublication dateApplicantTitle
US4165750 *Mar 9, 1978Aug 28, 1979Aleev Leonid SBioelectrically controlled electric stimulator of human muscles
US4201219 *Mar 3, 1978May 6, 1980Bozal Gonzalez Jose LCardiac pace-maker
US4243024 *Apr 2, 1979Jan 6, 1981The United States Of America As Represented By The Secretary Of The NavyG-Protection system sensing a change in acceleration and tilt angle
US4289140 *Aug 31, 1979Sep 15, 1981Carpenter David ASignal processing system
US4338945 *Mar 2, 1979Jul 13, 1982Clinical Engineering Laboratory LimitedMethod and randomized electrical stimulation system for pain relief
US4453547 *Apr 6, 1981Jun 12, 1984Physio Technology, Inc.T-Wave inhibiting system
US4509521 *Jan 31, 1983Apr 9, 1985Barry Terrence JHeadache relief method
US4566456 *Oct 18, 1984Jan 28, 1986Cordis CorporationApparatus and method for adjusting heart/pacer rate relative to right ventricular systolic pressure to obtain a required cardiac output
US4600017 *Jul 19, 1984Jul 15, 1986Cordis CorporationPacing lead with sensor
US4702254 *Dec 30, 1985Oct 27, 1987Jacob ZabaraMethod of controlling/preventing involuntary movements
US4763646 *Dec 9, 1987Aug 16, 1988Siemens AktiengesellschaftHeart pacemaker
US4770177 *Feb 18, 1986Sep 13, 1988Telectronics N.V.Apparatus and method for adjusting heart/pacer relative to changes in venous diameter during exercise to obtain a required cardiac output.
US4791931 *Aug 13, 1987Dec 20, 1988Pacesetter Infusion, Ltd.Demand pacemaker using an artificial baroreceptor reflex
US4860751 *Feb 4, 1985Aug 29, 1989Cordis CorporationActivity sensor for pacemaker control
US4867164 *Oct 26, 1987Sep 19, 1989Jacob ZabaraNeurocybernetic prosthesis
US5025807 *Jan 25, 1989Jun 25, 1991Jacob ZabaraNeurocybernetic prosthesis
US5083563 *Feb 16, 1990Jan 28, 1992Telectronics Pacing Systems, Inc.Implantable automatic and haemodynamically responsive cardioverting/defibrillating pacemaker
US5199428 *Mar 22, 1991Apr 6, 1993Medtronic, Inc.Implantable electrical nerve stimulator/pacemaker with ischemia for decreasing cardiac workload
US5458626 *Dec 27, 1993Oct 17, 1995Krause; Horst E.Method of electrical nerve stimulation for acceleration of tissue healing
US5540734 *Sep 28, 1994Jul 30, 1996Zabara; JacobCranial nerve stimulation treatments using neurocybernetic prosthesis
US5575809 *Jun 11, 1993Nov 19, 1996Kabushiki Kaisya AdvanceElectrical stimulator
US5578061 *Oct 3, 1995Nov 26, 1996Pacesetter AbMethod and apparatus for cardiac therapy by stimulation of a physiological representative of the parasympathetic nervous system
US5690681 *Mar 29, 1996Nov 25, 1997Purdue Research FoundationMethod and apparatus using vagal stimulation for control of ventricular rate during atrial fibrillation
US5700282 *Oct 13, 1995Dec 23, 1997Zabara; JacobHeart rhythm stabilization using a neurocybernetic prosthesis
US5707400 *Sep 19, 1995Jan 13, 1998Cyberonics, Inc.Treating refractory hypertension by nerve stimulation
US5727558 *Feb 14, 1996Mar 17, 1998Hakki; A-HamidNoninvasive blood pressure monitor and control device
US5916239 *Nov 24, 1997Jun 29, 1999Purdue Research FoundationMethod and apparatus using vagal stimulation for control of ventricular rate during atrial fibrillation
US6050952 *Jan 14, 1998Apr 18, 2000Hakki; A-HamidMethod for noninvasive monitoring and control of blood pressure
US6058331 *Apr 27, 1998May 2, 2000Medtronic, Inc.Apparatus and method for treating peripheral vascular disease and organ ischemia by electrical stimulation with closed loop feedback control
US6073048 *Nov 17, 1995Jun 6, 2000Medtronic, Inc.Baroreflex modulation with carotid sinus nerve stimulation for the treatment of heart failure
US6522926Sep 27, 2000Feb 18, 2003Cvrx, Inc.Devices and methods for cardiovascular reflex control
US6850801Sep 26, 2001Feb 1, 2005Cvrx, Inc.Mapping methods for cardiovascular reflex control devices
US6985774Sep 26, 2001Jan 10, 2006Cvrx, Inc.Stimulus regimens for cardiovascular reflex control
US7010345Oct 26, 2001Mar 7, 2006Medtronic, Inc.Method and apparatus to minimize effects of a cardiac insult
US7050856Jan 11, 2002May 23, 2006Medtronic, Inc.Variation of neural-stimulation parameters
US7155284Jan 16, 2003Dec 26, 2006Advanced Bionics CorporationTreatment of hypertension
US7158832Sep 26, 2001Jan 2, 2007Cvrx, Inc.Electrode designs and methods of use for cardiovascular reflex control devices
US7194313Jun 8, 2004Mar 20, 2007Cardiac Pacemakers, Inc.Baroreflex therapy for disordered breathing
US7218964Oct 26, 2001May 15, 2007Medtronic, Inc.Closed-loop neuromodulation for prevention and treatment of cardiac conditions
US7395119May 19, 2005Jul 1, 2008Cvrx, Inc.Implantable electrode assembly having reverse electrode configuration
US7460906Dec 24, 2003Dec 2, 2008Cardiac Pacemakers, Inc.Baroreflex stimulation to treat acute myocardial infarction
US7485104Jun 2, 2003Feb 3, 2009Cvrx, Inc.Systems and methods for controlling renovascular perfusion
US7486991 *Dec 24, 2003Feb 3, 2009Cardiac Pacemakers, Inc.Baroreflex modulation to gradually decrease blood pressure
US7499742Mar 27, 2003Mar 3, 2009Cvrx, Inc.Electrode structures and methods for their use in cardiovascular reflex control
US7502650 *Sep 21, 2004Mar 10, 2009Cvrx, Inc.Baroreceptor activation for epilepsy control
US7509166 *Dec 24, 2003Mar 24, 2009Cardiac Pacemakers, Inc.Automatic baroreflex modulation responsive to adverse event
US7542800Apr 5, 2005Jun 2, 2009Cardiac Pacemakers, Inc.Method and apparatus for synchronizing neural stimulation to cardiac cycles
US7555341Apr 5, 2005Jun 30, 2009Cardiac Pacemakers, Inc.System to treat AV-conducted ventricular tachyarrhythmia
US7596413Jun 8, 2004Sep 29, 2009Cardiac Pacemakers, Inc.Coordinated therapy for disordered breathing including baroreflex modulation
US7616997Mar 27, 2003Nov 10, 2009Kieval Robert SDevices and methods for cardiovascular reflex control via coupled electrodes
US7617005Aug 14, 2006Nov 10, 2009Ardian, Inc.Methods and apparatus for thermally-induced renal neuromodulation
US7620451Feb 27, 2006Nov 17, 2009Ardian, Inc.Methods and apparatus for pulsed electric field neuromodulation via an intra-to-extravascular approach
US7623926Apr 5, 2004Nov 24, 2009Cvrx, Inc.Stimulus regimens for cardiovascular reflex control
US7647114Sep 13, 2004Jan 12, 2010Cardiac Pacemakers, Inc.Baroreflex modulation based on monitored cardiovascular parameter
US7653438May 13, 2005Jan 26, 2010Ardian, Inc.Methods and apparatus for renal neuromodulation
US7657312Nov 3, 2003Feb 2, 2010Cardiac Pacemakers, Inc.Multi-site ventricular pacing therapy with parasympathetic stimulation
US7668594Aug 19, 2005Feb 23, 2010Cardiac Pacemakers, Inc.Method and apparatus for delivering chronic and post-ischemia cardiac therapies
US7706884Dec 24, 2003Apr 27, 2010Cardiac Pacemakers, Inc.Baroreflex stimulation synchronized to circadian rhythm
US7717948Aug 16, 2007May 18, 2010Ardian, Inc.Methods and apparatus for thermally-induced renal neuromodulation
US7734348May 10, 2005Jun 8, 2010Cardiac Pacemakers, Inc.System with left/right pulmonary artery electrodes
US7747323Jun 8, 2004Jun 29, 2010Cardiac Pacemakers, Inc.Adaptive baroreflex stimulation therapy for disordered breathing
US7756583Nov 4, 2005Jul 13, 2010Ardian, Inc.Methods and apparatus for intravascularly-induced neuromodulation
US7765000May 10, 2005Jul 27, 2010Cardiac Pacemakers, Inc.Neural stimulation system with pulmonary artery lead
US7765008 *Oct 31, 2007Jul 27, 2010Metacure LimitedMethod of controlling blood pressure
US7769441Nov 3, 2005Aug 3, 2010The Board Of Regents Of The University Of OklahomaCardiac neuromodulation and methods of using same
US7783353Nov 9, 2006Aug 24, 2010Cardiac Pacemakers, Inc.Automatic neural stimulation modulation based on activity and circadian rhythm
US7787946Sep 17, 2004Aug 31, 2010Cardiac Pacemakers, Inc.Patient monitoring, diagnosis, and/or therapy systems and methods
US7801614Oct 23, 2006Sep 21, 2010Cvrx, Inc.Stimulus regimens for cardiovascular reflex control
US7813812Jul 7, 2006Oct 12, 2010Cvrx, Inc.Baroreflex stimulator with integrated pressure sensor
US7840271 *Jul 20, 2005Nov 23, 2010Cvrx, Inc.Stimulus regimens for cardiovascular reflex control
US7853333Jun 12, 2006Dec 14, 2010Ardian, Inc.Methods and apparatus for multi-vessel renal neuromodulation
US7860563Nov 23, 2005Dec 28, 2010The Board Of Regents Of The University Of OklahomaCardiac neuromodulation and methods of using same
US7869881Dec 24, 2003Jan 11, 2011Cardiac Pacemakers, Inc.Baroreflex stimulator with integrated pressure sensor
US7873413Jul 24, 2006Jan 18, 2011Cardiac Pacemakers, Inc.Closed loop neural stimulation synchronized to cardiac cycles
US7873418Apr 28, 2006Jan 18, 2011Medtronic, Inc.Variation of neural stimulation parameters
US7925352Mar 27, 2009Apr 12, 2011Synecor LlcSystem and method for transvascularly stimulating contents of the carotid sheath
US7937143Oct 18, 2005May 3, 2011Ardian, Inc.Methods and apparatus for inducing controlled renal neuromodulation
US7949400Nov 10, 2009May 24, 2011Cvrx, Inc.Devices and methods for cardiovascular reflex control via coupled electrodes
US7962216 *Apr 16, 2008Jun 14, 2011National Cerebral And Cardiovascular CenterCardiac pacing system, blood pressure regulating system, and cardiac disease treatment system by substituting native biological regulatory function
US7966071Oct 31, 2007Jun 21, 2011Metacure LimitedMethod and apparatus for regulating glucose level
US8000793May 23, 2008Aug 16, 2011Cardiac Pacemakers, Inc.Automatic baroreflex modulation based on cardiac activity
US8002553Aug 18, 2003Aug 23, 2011Cardiac Pacemakers, Inc.Sleep quality data collection and evaluation
US8002718 *Jun 30, 2006Aug 23, 2011Siemens AktiengesellschaftShockwave system control dependent on patient's blood pressure
US8005539Jan 30, 2009Aug 23, 2011Medtronic, Inc.Implantable medical device crosstalk evaluation and mitigation
US8010195Feb 18, 2011Aug 30, 2011National Cerebral And Cardiovascular CenterCardiac pacing system by substituting native biological regulatory function
US8010199Feb 23, 2011Aug 30, 2011National Cerebral And Cardiovascular CenterBlood pressure regulating system by substituting native biological regulatory function
US8024050Dec 24, 2003Sep 20, 2011Cardiac Pacemakers, Inc.Lead for stimulating the baroreceptors in the pulmonary artery
US8060206 *Jul 7, 2006Nov 15, 2011Cvrx, Inc.Baroreflex modulation to gradually decrease blood pressure
US8086314 *Oct 29, 2002Dec 27, 2011Cvrx, Inc.Devices and methods for cardiovascular reflex control
US8109879Jan 10, 2006Feb 7, 2012Cardiac Pacemakers, Inc.Assessing autonomic activity using baroreflex analysis
US8116883Feb 2, 2007Feb 14, 2012Synecor LlcIntravascular device for neuromodulation
US8121693Oct 23, 2008Feb 21, 2012Cardiac Pacemakers, Inc.Baroreflex stimulation to treat acute myocardial infarction
US8126560Dec 24, 2003Feb 28, 2012Cardiac Pacemakers, Inc.Stimulation lead for stimulating the baroreceptors in the pulmonary artery
US8131371Apr 13, 2006Mar 6, 2012Ardian, Inc.Methods and apparatus for monopolar renal neuromodulation
US8131372Mar 19, 2007Mar 6, 2012Ardian, Inc.Renal nerve stimulation method for treatment of patients
US8131373Mar 30, 2010Mar 6, 2012Cardiac Pacemakers, Inc.Baroreflex stimulation synchronized to circadian rhythm
US8140155Mar 10, 2009Mar 20, 2012Cardiac Pacemakers, Inc.Intermittent pacing therapy delivery statistics
US8145316Jul 25, 2005Mar 27, 2012Ardian, Inc.Methods and apparatus for renal neuromodulation
US8145317Mar 6, 2006Mar 27, 2012Ardian, Inc.Methods for renal neuromodulation
US8150518Jun 3, 2005Apr 3, 2012Ardian, Inc.Renal nerve stimulation method and apparatus for treatment of patients
US8150519Mar 6, 2006Apr 3, 2012Ardian, Inc.Methods and apparatus for bilateral renal neuromodulation
US8150520Mar 6, 2006Apr 3, 2012Ardian, Inc.Methods for catheter-based renal denervation
US8175705Oct 12, 2004May 8, 2012Cardiac Pacemakers, Inc.System and method for sustained baroreflex stimulation
US8175711Mar 6, 2006May 8, 2012Ardian, Inc.Methods for treating a condition or disease associated with cardio-renal function
US8190257May 28, 2009May 29, 2012Cardiac Pacemakers, Inc.System to treat AV-conducted ventricular tachyarrhythmia
US8219201Apr 17, 2007Jul 10, 2012Metacure LimitedSmooth muscle controller for controlling the level of a chemical in the blood stream
US8224437Oct 3, 2008Jul 17, 2012Cvrx, Inc.Baroreflex activation for sedation and sleep
US8249705Mar 6, 2008Aug 21, 2012Cvrx, Inc.Devices, systems, and methods for improving left ventricular structure and function using baroreflex activation therapy
US8249708Jan 30, 2009Aug 21, 2012Medtronic, Inc.Implantable medical device crosstalk evaluation and mitigation
US8260412Jan 30, 2009Sep 4, 2012Medtronic, Inc.Implantable medical device crosstalk evaluation and mitigation
US8285389Jul 21, 2010Oct 9, 2012Cardiac Pacemakers, Inc.Automatic neural stimulation modulation based on motion and physiological activity
US8290595 *Jul 7, 2006Oct 16, 2012Cvrx, Inc.Method and apparatus for stimulation of baroreceptors in pulmonary artery
US8306615Jan 18, 2010Nov 6, 2012Cardiac Pacemakers, Inc.Method and apparatus for delivering chronic and post-ischemia cardiac therapies
US8315713Apr 30, 2009Nov 20, 2012Medtronic, Inc.Techniques for placing medical leads for electrical stimulation of nerve tissue
US8321023Jan 27, 2009Nov 27, 2012Cardiac Pacemakers, Inc.Baroreflex modulation to gradually decrease blood pressure
US8347891Nov 14, 2006Jan 8, 2013Medtronic Ardian Luxembourg S.A.R.L.Methods and apparatus for performing a non-continuous circumferential treatment of a body lumen
US8355789Apr 28, 2006Jan 15, 2013Medtronic, Inc.Method and apparatus providing asynchronous neural stimulation
US8369954Mar 7, 2011Feb 5, 2013Synecor LlcSystem and method for transvascularly stimulating contents of the carotid sheath
US8396556Dec 15, 2010Mar 12, 2013Cardiac Pacemakers, Inc.Transcutaneous neurostimulator for treating hypertension
US8406876Jan 15, 2010Mar 26, 2013Cardiac Pacemakers, Inc.Closed loop neural stimulation synchronized to cardiac cycles
US8417334 *Oct 26, 2001Apr 9, 2013Medtronic, Inc.Method and apparatus for electrically stimulating the nervous system to improve ventricular dysfunction, heart failure, and other cardiac conditions
US8417354May 13, 2010Apr 9, 2013Cardiac Pacemakers, Inc.Methods for using a pulmonary artery electrode
US8433423Dec 13, 2010Apr 30, 2013Ardian, Inc.Methods for multi-vessel renal neuromodulation
US8442638May 17, 2010May 14, 2013Cardiac Pacemakers, Inc.Adaptive baroreflex stimulation therapy for disordered breathing
US8442640Jan 4, 2010May 14, 2013Cardiac Pacemakers, Inc.Neural stimulation modulation based on monitored cardiovascular parameter
US8444640Sep 14, 2012May 21, 2013Medtronic Ardian Luxembourg S.A.R.L.Methods and apparatus for performing a non-continuous circumferential treatment of a body lumen
US8452394Jan 30, 2009May 28, 2013Medtronic, Inc.Implantable medical device crosstalk evaluation and mitigation
US8452398May 20, 2009May 28, 2013Cardiac Pacemakers, Inc.Method and apparatus for synchronizing neural stimulation to cardiac cycles
US8454594Aug 11, 2009Jun 4, 2013Medtronic Ardian Luxembourg S.A.R.L.Apparatus for performing a non-continuous circumferential treatment of a body lumen
US8457746Aug 4, 2011Jun 4, 2013Cardiac Pacemakers, Inc.Implantable systems and devices for providing cardiac defibrillation and apnea therapy
US8473057Oct 30, 2009Jun 25, 2013Medtronic, Inc.Shunt-current reduction housing for an implantable therapy system
US8473076Sep 6, 2011Jun 25, 2013Cardiac Pacemakers, Inc.Lead for stimulating the baroreceptors in the pulmonary artery
US8478414Apr 30, 2008Jul 2, 2013Cvrx, Inc.Baroreflex activation for pain control, sedation and sleep
US8498698Aug 31, 2009Jul 30, 2013Medtronic, Inc.Isolation of sensing and stimulation circuitry
US8527045Oct 30, 2009Sep 3, 2013Medtronic, Inc.Therapy system including cardiac rhythm therapy and neurostimulation capabilities
US8527064Dec 3, 2008Sep 3, 2013Cardiac Pacemakers, Inc.System for stimulating autonomic targets from pulmonary artery
US8532779Jan 30, 2009Sep 10, 2013Medtronic, Inc.Implantable medical device crosstalk evaluation and mitigation
US8532793Apr 30, 2009Sep 10, 2013Medtronic, Inc.Techniques for placing medical leads for electrical stimulation of nerve tissue
US8535222Mar 13, 2007Sep 17, 2013Cardiac Pacemakers, Inc.Sleep detection using an adjustable threshold
US8538535Aug 5, 2010Sep 17, 2013Rainbow Medical Ltd.Enhancing perfusion by contraction
US8548585Dec 7, 2010Oct 1, 2013Cardiac Pacemakers, Inc.Concurrent therapy detection in implantable medical devices
US8548600Sep 14, 2012Oct 1, 2013Medtronic Ardian Luxembourg S.A.R.L.Apparatuses for renal neuromodulation and associated systems and methods
US8551069Mar 6, 2006Oct 8, 2013Medtronic Adrian Luxembourg S.a.r.l.Methods and apparatus for treating contrast nephropathy
US8560060Aug 31, 2009Oct 15, 2013Medtronic, Inc.Isolation of sensing and stimulation circuitry
US8560076Nov 5, 2010Oct 15, 2013Cvrx, Inc.Devices and methods for electrode implantation
US8571655Jan 26, 2010Oct 29, 2013Cardiac Pacemakers, Inc.Multi-site ventricular pacing therapy with parasympathetic stimulation
US8571687Aug 26, 2010Oct 29, 2013Cardiac Pacemakers, Inc.Transcutaneous neurostimulator for modulating cardiovascular function
US8583236Mar 8, 2010Nov 12, 2013Cvrx, Inc.Devices and methods for cardiovascular reflex control
US8594794Jul 17, 2008Nov 26, 2013Cvrx, Inc.Baroreflex activation therapy with incrementally changing intensity
US8606356Aug 17, 2004Dec 10, 2013Cardiac Pacemakers, Inc.Autonomic arousal detection system and method
US8606359Apr 13, 2007Dec 10, 2013Cvrx, Inc.System and method for sustained baroreflex stimulation
US8611996Jan 30, 2009Dec 17, 2013Medtronic, Inc.Implantable medical device crosstalk evaluation and mitigation
US8620423Mar 14, 2011Dec 31, 2013Medtronic Ardian Luxembourg S.A.R.L.Methods for thermal modulation of nerves contributing to renal function
US8626282Nov 15, 2012Jan 7, 2014Cardiac Pacemakers, Inc.Baroreflex modulation to gradually change a physiological parameter
US8626290Aug 16, 2011Jan 7, 2014Enopace Biomedical Ltd.Acute myocardial infarction treatment by electrical stimulation of the thoracic aorta
US8626299Dec 1, 2010Jan 7, 2014Enopace Biomedical Ltd.Thoracic aorta and vagus nerve stimulation
US8626300Mar 11, 2011Jan 7, 2014Medtronic Ardian Luxembourg S.A.R.L.Methods and apparatus for thermally-induced renal neuromodulation
US8626301Jun 3, 2013Jan 7, 2014Cardiac Pacemakers, Inc.Automatic baroreflex modulation based on cardiac activity
US8649863Dec 20, 2010Feb 11, 2014Rainbow Medical Ltd.Pacemaker with no production
US8657756Feb 15, 2011Feb 25, 2014Cardiac Pacemakers, Inc.Implantable device employing movement sensing for detecting sleep-related disorders
US8660648Nov 15, 2012Feb 25, 2014Cardiac Pacemakers, Inc.Implantable and rechargeable neural stimulator
US8666495Mar 18, 2005Mar 4, 2014Metacure LimitedGastrointestinal methods and apparatus for use in treating disorders and controlling blood sugar
US8684998Mar 9, 2012Apr 1, 2014Medtronic Ardian Luxembourg S.A.R.L.Methods for inhibiting renal nerve activity
US8688210Jan 30, 2009Apr 1, 2014Medtronic, Inc.Implantable medical device crosstalk evaluation and mitigation
US8688211Aug 26, 2010Apr 1, 2014Cardiac Pacemakers, Inc.Percutaneous neurostimulator for modulating cardiovascular function
US8694119May 13, 2010Apr 8, 2014Samson Neurosciences Ltd.Endovascular electrostimulation near a carotid bifurcation in treating cerebrovascular conditions
US8712522Oct 18, 2005Apr 29, 2014Cvrx, Inc.System for setting programmable parameters for an implantable hypertension treatment device
US8712531May 24, 2012Apr 29, 2014Cvrx, Inc.Automatic baroreflex modulation responsive to adverse event
US8718789Apr 19, 2010May 6, 2014Cvrx, Inc.Electrode structures and methods for their use in cardiovascular reflex control
US8721637Jul 12, 2013May 13, 2014Medtronic Ardian Luxembourg S.A.R.L.Methods and apparatus for performing renal neuromodulation via catheter apparatuses having inflatable balloons
US8728137Feb 12, 2013May 20, 2014Medtronic Ardian Luxembourg S.A.R.L.Methods for thermally-induced renal neuromodulation
US8728138Feb 12, 2013May 20, 2014Medtronic Ardian Luxembourg S.A.R.L.Methods for thermally-induced renal neuromodulation
US8740825Aug 22, 2013Jun 3, 2014Sympara Medical, Inc.Methods and devices for treating hypertension
US8740896Jul 12, 2013Jun 3, 2014Medtronic Ardian Luxembourg S.A.R.L.Methods and apparatus for performing renal neuromodulation via catheter apparatuses having inflatable balloons
US8747338Aug 22, 2013Jun 10, 2014Sympara Medical, Inc.Methods and devices for treating hypertension
US8755907May 21, 2013Jun 17, 2014Cvrx, Inc.Devices and methods for electrode implantation
US8768469Aug 6, 2009Jul 1, 2014Enteromedics Inc.Systems for regulation of blood pressure and heart rate
US8768470May 11, 2010Jul 1, 2014Medtronic Ardian Luxembourg S.A.R.L.Methods for monitoring renal neuromodulation
EP2085114A2 *Sep 27, 2001Aug 5, 2009CVRX, Inc.Devices and methods for cardiovascular reflex control
EP2233172A1 *Oct 15, 2008Sep 29, 2010Kyushu University, National University CorporationBlood pressure stabilization system using transdermal stimulation
EP2399644A2 *Sep 27, 2001Dec 28, 2011CVRX, Inc.Devices for cardiovascular reflex control
EP2446924A1 *Jun 15, 2007May 2, 2012Cardiac Pacemakers, Inc.Transcutaneous neurostimulator for modulating cardiovascular function
WO1985001213A1 *Sep 11, 1984Mar 28, 1985Jacob ZabaraNeurocybernetic prosthesis
WO1995017921A1 *Dec 27, 1994Jul 6, 1995Horst Edgar KrauseMethod of electrical nerve stimulation
WO1999055413A1 *Apr 9, 1999Nov 4, 1999Medtronic IncApparatus for treating peripheral vascular disease and organ ischemia
WO2002026314A1 *Sep 27, 2001Apr 4, 2002Cvrx IncDevices and methods for cardiovascular reflex control
WO2002028478A1 *Oct 3, 2001Apr 11, 2002Kjellman CharlotteImplantable medical device with pressure measurement means
WO2002034327A2Oct 26, 2001May 2, 2002Medtronic IncMethod and apparatus to minimize the effects of a cardiac insult
WO2002034330A2Oct 26, 2001May 2, 2002Medtronic IncMethod and apparatus to minimize the effects of a cardiac insult
WO2002096512A1Oct 26, 2001Dec 5, 2002Medtronic IncClosed-loop neuromodulation for prevention and treatment of cardiac conditions
WO2003076008A1 *Mar 13, 2003Sep 18, 2003Brainsgate LtdTechnique for blood pressure regulation
WO2006044025A1 *Aug 19, 2005Apr 27, 2006Cardiac Pacemakers IncSystem for sustained baroreflex stimulation
WO2006107675A1Mar 29, 2006Oct 12, 2006Cardiac Pacemakers IncCardiac cycle - synchronized neural stimulator
WO2007076281A1Dec 13, 2006Jul 5, 2007Medtronic IncSystem and method for regulating blood pressure and electrolyte balance
WO2010131219A1May 13, 2010Nov 18, 2010Samson Neurosciences Ltd.Endovascular electrostimulation near a carotid bifurcation in treating cerebrovascular conditions
Classifications
U.S. Classification607/44, 607/72, 607/62
International ClassificationA61N1/365, A61N1/32, A61B5/0215, A61N1/36, A61N1/372
Cooperative ClassificationA61N1/36564, A61N1/36117, A61B5/0215, A61B5/7239
European ClassificationA61B5/0215, A61N1/365B9