U.S. patent number 3,650,277 [Application Number 05/012,062] was granted by the patent office on 1972-03-21 for apparatus for influencing the systemic blood pressure in a patient by carotid sinus nerve stimulation.
This patent grant is currently assigned to LKB Medical AB. Invention is credited to Per Ake Oberg, Ulf Hakan Sjostrand.
United States Patent |
3,650,277 |
Sjostrand , et al. |
March 21, 1972 |
APPARATUS FOR INFLUENCING THE SYSTEMIC BLOOD PRESSURE IN A PATIENT
BY CAROTID SINUS NERVE STIMULATION
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.
Inventors: |
Sjostrand; Ulf Hakan (Uppsala,
SW), Oberg; Per Ake (Brunna, SW) |
Assignee: |
LKB Medical AB (Bromma,
SW)
|
Family
ID: |
20260112 |
Appl.
No.: |
05/012,062 |
Filed: |
February 17, 1970 |
Foreign Application Priority Data
Current U.S.
Class: |
607/44; 607/62;
607/72 |
Current CPC
Class: |
A61B
5/0215 (20130101); A61N 1/36564 (20130101); A61B
5/7239 (20130101); A61N 1/36117 (20130101) |
Current International
Class: |
A61B
5/0215 (20060101); A61N 1/365 (20060101); A61N
1/372 (20060101); A61n 001/36 () |
Field of
Search: |
;128/418,419R,421,422,423,2.5A,2.5P,2.5E,2.5M,2.5B,2.5R,2.6A |
References Cited
[Referenced By]
U.S. Patent Documents
Other References
Bilgutay et al., "Transactions of American Society of Artificial
Internal Organs," Vol. X, 1964, pp. 387-393.
|
Primary Examiner: Kamm; William E.
Claims
What is claimed is:
1. 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;
2. 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
5. 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 generator having two outputs for said
output pulses;
5. stimulator means including right 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.
Description
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
FIG. 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;
FIG. 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 (FIG. 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 10 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
P.sub.mean = P.sub.diastolic + 1/.sqroot.2 (P.sub.systolic -
P.sub.diastolic)
This is an approximative expression for the arterial mean blood
pressure P.sub.mean 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 of a signal adding amplifier 13. By
means of the 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 11
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 13 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 12 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 communication 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 10 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 step-function
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 experiment. 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.sub.1 and reopened at the time T.sub.2. 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.sub.2 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.sub.2
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 11
dependent on the derivative of the blood pressure was supplied to
the adder amplifier 13 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 0 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 frequency respectively 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
1-5 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.
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