WO2002066112A1 - Appareil servant a traiter un organisme vivant pour parvenir a une reduction de la sollicitation cardiaque et procede permettant d'obtenir une reduction de la sollicitation cardiaque - Google Patents

Appareil servant a traiter un organisme vivant pour parvenir a une reduction de la sollicitation cardiaque et procede permettant d'obtenir une reduction de la sollicitation cardiaque Download PDF

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Publication number
WO2002066112A1
WO2002066112A1 PCT/EP2002/001779 EP0201779W WO02066112A1 WO 2002066112 A1 WO2002066112 A1 WO 2002066112A1 EP 0201779 W EP0201779 W EP 0201779W WO 02066112 A1 WO02066112 A1 WO 02066112A1
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WIPO (PCT)
Prior art keywords
heart rhythm
heart
rhythm
signals
accordance
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PCT/EP2002/001779
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English (en)
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WO2002066112A9 (fr
Inventor
Larry V. Lapanashvili
Christian STÜRZINGER
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Cardiorest Ltd.
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Publication of WO2002066112A1 publication Critical patent/WO2002066112A1/fr
Publication of WO2002066112A9 publication Critical patent/WO2002066112A9/fr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/18—Applying electric currents by contact electrodes
    • A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
    • A61N1/36014—External stimulators, e.g. with patch electrodes
    • A61N1/3603—Control systems
    • A61N1/36031—Control systems using physiological parameters for adjustment
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/18—Applying electric currents by contact electrodes
    • A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
    • A61N1/36014—External stimulators, e.g. with patch electrodes
    • A61N1/3603—Control systems
    • A61N1/36034—Control systems specified by the stimulation parameters
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N1/00—Electrotherapy; Circuits therefor
    • A61N1/18—Applying electric currents by contact electrodes
    • A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
    • A61N1/36—Applying electric currents by contact electrodes alternating or intermittent currents for stimulation
    • A61N1/362—Heart stimulators
    • A61N1/365—Heart stimulators controlled by a physiological parameter, e.g. heart potential
    • A61N1/36585—Heart stimulators controlled by a physiological parameter, e.g. heart potential controlled by two or more physical parameters

Definitions

  • Apparatus for treating a living organism to achieve a heart load reduction and a method of achieving a heart load reduction
  • the present invention relates to an apparatus for treating a mammal or other living organism having a heart and a peripheral vascular system, in particular a human being to achieve a heart load reduction and a whole variety of other treatments and associated benefits as well as to a method of achieving a heart load reduction.
  • An electrocardiogram is basically a record of the sequence of electrical waves generated at each heart beat and the different peaks of the typical electrocardiogram are usually designated by the let- - ters P, Q, R, S and T.
  • the so-called R-R path i.e. the time between two R peaks represents one cycle of the heart and normally amounts to about 1 second.
  • Cardiologists frequently refer to the concept of the heart load which is proportional to the heart pulse rate, i.e. the frequency of R-R waves measured in heart beats per minute, multiplied by the systolic blood pressure as measured in millimeters of mercury.
  • Electrophysiological interactions with living bodies in general, and human beings in particular, can be classified into two main groups, namely asynchronous and cardiosynchronized electrophysiological interactions.
  • Asynchronous electrophysiological methods and apparatus operate using electrostimulation in which the stimulation is timed in accordance with some externally imposed rhythm, but this timing is not synchronized with the heart pulse rate.
  • asynchronous electrophysiological methods and apparatus include: neurostimulation and neuromuscular and direct muscular stimulation by electrostimulators, with equipment being available from Medicompex SA, Valmed SA, Nemectron GmbH, and EMPI Inc. among others, the use of electrostimulation for the therapy of pain, with equipment being available from Medtronic Inc. among others, electrostimulation for active tremor control therapy, for which Medtronic Inc. among others supplies equipment and electrostimulation for urinary control, again with apparatus being offered by, for example, Medtronic Inc., such as that company's In- terstim product.
  • the other basic category of electrophysiological techniques namely car- diosynchronized electrophysiological methods and apparatus, comprise methods by which the heart pulse rate is predetermined by means of a sensor and stimulation is delivered in a rhythm at any time within the heart pulse rate and is synchronized with the heart pulse rate.
  • Such cardiosynchronized methods and apparatus can be subdivided into two classes, namely the simpulsation mode and the counterpulsation mode.
  • the electric impulses are synchronized with the heart pulse rate so that the heart and the stimulated muscle are contracting at the same time, i.e. in systole phase the heart is contracting and the stimulated muscle is contracting. In the diastole phase the heart is relaxing and the muscle is relaxing.
  • the electric impulses are timed in such a way relative to the heart pulse rate, that the heart and the stimulated muscle are contracting in opposition to each other, i.e. in the systole phase the heart is contracting and the stimulated muscle is relaxing, in the diastole phase the heart is relaxing and the stimulated muscle is contracting.
  • a principal object of the earlier invention is to provide an almost universally applicable method and apparatus by which a substantial degree of heart unloading can be achieved by appropriate non-invasive or invasive stimulation of the patient which can be applied without practical time limitation and in particular without any restrictions of the muscles to be stimulated, with the exception of the heart muscle itself. This object also applies to the present invention.
  • a further object of the present invention is to provide apparatus and methods which avoid the need for continuous monitoring of the patient's heartbeat, thereby simplifying the apparatus and making the use of the apparatus more pleasant and less complicated for the patient.
  • neuro- neuromusclar or direct muscular anti-pain stimulation including traricutaneous electrical nerve stimulation (frequently called TENS) as well as for many other applications of aesthetic and curative medicine.
  • TENS traricutaneous electrical nerve stimulation
  • apparatus for treating a mammal or other living organism having a heart exhibiting a heart rhythm with alternating phases of systole and diastole, a peripheral vascular system, and a systolic pressure resulting from the action of the heart, the apparatus comprising a heart rhythm sensor, a pulse generator for generating electrical stimulating signals synchronized with the heart rhythm and timed to occur during phases of diastole, at least first and second electrodes for applying the electrical stimulation signals to one or more skeletal or smooth muscles associated with said peripheral vascular system, and a sound generator for producing acoustic signals with a pulse repetition frequency corresponding to a heart rhythm, wherein the heart rhythm to which the pulse repetition frequency corresponds is the heart rhythm sensed by the heart rhythm sensor, wherein the electrical stimulating signals are triggered in a time window lying within a range of 5% of the length of the R-R path before the end of the T wave and 45% of the
  • the present invention proposes that the proband is subjected simultaneously to electrical stimulatirig signals and acoustic stimulating signals. It has namely been ⁇ . found that this type of joint stimulation leads to a more rapid and reliable reduction of the proband's heart rhythm which, on the one hand, reduces the overall treatment time required and, on the other hand, seems to make it easier to treat "difficult" probands who are not able to relax easily and have a certain inherent resistance to achieving the full benefit of the treatment.
  • Another advantage which is particularly beneficial is the fact that the acoustic signals are only generated when the electrical stimulating signals are generated so that if the acoustic signal stops for some reason the proband or the person administering the treatment is alerted to the fact that something is amiss. This can for example be because one of the electrodes is not making good electrical contact to the proband, or because the apparatus has failed in some way, which might otherwise not be noticed by the proband, if he or she is for example in a state of deep rest, or by the person administering the treatment if attending to other duties at the same time.
  • an apparatus for treating a mammal or other living organism having a heart exhibiting a heart rhythm with alternating phases of systole and diastole, a peripheral vascular system, and a systolic pressure resulting from the action of the heart comprising a heart rhythm sensor, a pulse generator for generating electrical stimulating signals synchronized with the heart rhythm and timed to occur during phases of diastole, at least first and second electrodes for applying the electrical stimulation signals to one or more skeletal or smooth muscles associated with said peripheral vascular system, and a sound generator for producing acoustic signals with a pulse repetition frequency corresponding to a heart rhythm, wherein the heart rhythm to which the pulse repetition frequency is related is an artificial heart rhythm slower over at least portion of a treatment period than the heart rhythm sensed by the heart -rhythm sen- - - sor.
  • This embodiment rates to a particularly preferred system in which the acoustic treatment of a patient is, initially at least, decoupled from the electrical stimulating signals.
  • the British patent 1 359 005 suggests an apparatus for using relaxation therapy comprising a sensing device which in use senses a bodily function and provides an electrical signal corresponding in frequency and/ or amplitude to the bodily function which is one of the following: -respiratory excursion motion; heart or pulse beat; muscle action; blood pressure; electronic control and transducing means; and . ..
  • a sensory stimulus generator adapted to stimulate the eye, ear or skin; with the said signal being passed to the control and transducing means which in use produces and passes a transduced signal substantially unaltered in respect of the form of the said frequency and/ or amplitude to activate the stimulus generator.
  • the stimulus generator may be adapted to vary the amplitude or frequency of the stimulus.
  • this type of bio-feedback is exploited in order to intentionally drive the proband' s heart rhythm to a lower frequency by subjecting the- proband to acoustic signals the fre- •-• quency which is progressively reduced in accordance with an artificial heart rhythm function.
  • This artificial heard rhythm function is, initially at least, different from the proband's actual heart rhythm.
  • electrical stimulation takes place with electrical stimulating signals synchronized to the proband's actual heart rhythm
  • the proband is exposed to acoustic signals which are initially at least slower than the proband's actual heart rhythm and the difference in frequency is used to drive down the proband's heart rate so that it reliably and quickly reaches a significantly lower level thus achieving the desired unloading of the heart.
  • the electrical stimulating signals are affecting the pro- band's blood pressure in the same way as described in connection with the earlier applications (and also herein in connection with a discussion of Fig. 3) and it is believed that the acoustic stimulation also plays a supplementary role in beneficially affecting the patient's blood pressure,- so .
  • the heart unloading results, on the one hand, due to a lowering of the heart beat and, on the other hand, by a lowering of the systolic pressure which, together with the heart beat, determines the heart load.
  • Preferred embodiments of the apparatus of the second aspect- of the invention are set forth in the subordinate claims 4 to 13 and indeed the preferred embodiments of claims 11, 12 and 13 are also applicable to the first aspect of the invention.
  • the proband ' is : how subjected to J electrical stimulation and to acoustic - : »' ⁇ .>- stimulation which is no longer synchronized to the patient's own heart.
  • this may also be a viable way of exploiting bio-feedback to produce a reduction in the heart load of a pro- band with the associated benefits.
  • Such a system has the benefit that an actual heart rhythm sensor is no longer required which significantly sim- plifies the timing of the electrical stimulating signals and of the acoustic signals, since these are both essentially triggered from an artificial heart rhythm which is generated or stored in a corresponding piece of electronic equipment.
  • biofeedback will ensure that the patient's actual heart rhythm is affected in such a way that as the artificial heart rhythm reduces, the patient's own heart rhythm will reduce and the two heart rhythms may end up being essentially the same, i.e. having the same frequency after an initial period of time, of say 20 minutes.
  • a situation may, however, also arise in which there is always a difference in frequency between the proband's actual heart rhythm and the artificial heart rhythm.
  • an artificial heart rhythm which may simply comprise a rectangular pulse at points in time simulating the R-peaks of an electrocardiogram is perfectly adequate to enable the mathematical calculation of the end of the T-wave (by using Bazett's relationship), so that the electrical stimulating signals and the acoustic signals can be timed in precisely the same manner described in the earlier invention and also further described herein with respect to Fig. 3.
  • the present invention also relates to methods related to the first, second and third aspects of the invention and set forth in the claims 26 to 28.
  • the present invention will now be explained in more detail in the following with reference to preferred embodiments and to the accompanying drawings in which are shown:
  • Fig. 1A a schematic diagram illustrating a typical electrocardiogram
  • Fig. IB a schematic diagram of the human heart
  • Fig. IC an enlarged view of the aorta at the junction with the heart and with the coronary arteries
  • Fig. 2A a schematic diagram of a first variant of an apparatus for applying electrostimulation in accordance with the invention of USSN 09/378, 181 and the related PCT and EP applications,
  • Fig. 2B a graph illustrating the terminology used to describe a bi- phasic rectangular impulse
  • Fig. 2C a graph illustrating the timing of the pulses applied to a patient in the counterpulsation mode to achieve cardioresonance in accordance with the invention
  • Fig. 3 a set of diagrams showing the effect of the method and apparatus of the invention on the operation of the heart of a pa- , . , ..tient,
  • Fig. 4 a block circuit diagram illustrating the operation of the apparatus of the variant of Fig. 2A
  • Fig. 5A a diagram illustrating an alternative method of stimulating a patient in accordance with the present invention by using an acoustic source
  • Fig. 5B a flow diagram illustrating the operation of the apparatus of Fig. 14A
  • FIGS. 6A-C diagrams illustrating an apparatus in accordance with a second aspect of the present invention
  • FIGs. 7A and 7B diagrams illustrating an apparatus in accordance with a first aspect of the present invention
  • FIGs. 8A-C diagrams illustrating an apparatus in accordance with the third aspect of the present invention.
  • FIG. 9A-G Figures illustrating a variety of possible different acoustic signals.
  • FIG. 1A, IB and 1C a brief description of the normal operation of the human heart will be given in order to facilitate an understanding of the present invention: ⁇ ⁇ • • - ⁇
  • the heart 10 shown in Fig. IB has four chambers, namely the right atrium RA, the right ventricle RV, the left ventricle LV, and the left atrium LA.
  • Venous blood returning to the heart flows into the right atrium, then into the right ventricle and passes to the lungs via the pulmonary artery PA.
  • the blood picks up oxygen and returns to the left atrium LA, as indicated by the arrow 14. From there, the oxygenated blood passes into the left ventricle, and then into the aorta AO where it starts on its journey through the so-called big circulation around the body.
  • the circulation from the right ventricle to the lungs and then to the left atrium is called the minor circulation.
  • the operation of the heart is associated with electrical signals, which are shown..on_the electrocardiogram. of Fig. 1 A.
  • the point P signifies the contraction of the two atriums RA and LA, which pushes blood into the respective ventricles RV and LV via the respective valves 16 and 18, which act as non-return valves.
  • the section of the electrocardiogram starting with Q and ending with T is referred to as the systole and represents the ventricle contraction which serves to expel blood from the right ventricle into the pulmonary artery, and from the left ventricle into the aorta.
  • the valves 16 and 18 are closed to prevent reverse flow into the right atrium and left atrium.
  • the section TQ is referred to as the diastole, meaning the relaxation or expansion of the ventricles.
  • the heart is supplied with oxygenated blood via the coronary arteries CA, which branch off from the aorta just upstream of the valves 20, 22, which close to prevent blood returning from the aorta to the left ventricle during the diastolic phase.
  • the heart itself a muscle, must be supplied with oxygenated blood to keep the muscles working.
  • the heart is supplied with this oxygenated blood via the coronary arteries CA during diastole.
  • the valves 20, 22 of the aorta AO are closed and at this time the blood pressure in the aorta causes blood to enter the coronary arteries CA.
  • an increase of the pressure in the aorta AO during diastole favors the coronary arteries.
  • one of the important results of the present invention is a small increase in pressure in the aorta during diastole and this has been found to have a profound effect on the operation of the heart muscle.
  • Fig. 2A shows an illustration of a basic apparatus which has been used for the testing of the invention of USSN 09/378, 181, an understanding of which .will facilitate and understanding of. the present invention., .
  • a patient 24 is shown lying on a bed 26 and is connected to an electrocardioscope 28 via, in this embodiment, three sensing electrodes 30, which enable the electrocardioscope to show the ECG trace 32 for the particular patient 24 on the display 34.
  • a signal is extracted corresponding to the repetition frequency of the path R- R of the ECG trace of Fig. 1 A. That is to say, this signal represents the frequency at which the patient's heart beats, i.e. his pulse rate.
  • This signal is fed to a pulse generator 36 via a line 38 which is not shown in Fig. 2A but which is schematically illustrated in the diagram of Fig. 4 relating to the operation of the apparatus of Fig. 2A.
  • the pulse generator 36 delivers a train of biphasic rectangular pulses to the patient 24 via the active electrodes 40, of which four are shown in Fig. 2A.
  • the further electrode 42 is a neutral electrode necessary to complete the circuit.
  • the train of pulses 44 is triggered once per cycle of a patient's heart and is timed to coincide with the end of the T- phase of the ECG.
  • the train of pulses 44 is also shown on the display 34 of the ECG, which enables the operator 46 to see the phase relationship between the train of pulses 44 and the electrocardiogram 34. From the joint display of the ECG and the train of pulses 44 on the screen 34 of the electrocardioscope, the operator 46 can see whether the train of pulses has the appropriate delay relative to the Q-wave to secure the cardioresonance desired in accordance with the invention.
  • the train of pulses is preferably set to start at the end of the T-wave.
  • the operator 46 is able to adjust the phase for the start of each train of pulses, i.e. the delay, so that it coincides with the end of the T-wave. This is one manual input into the pulse generator indicated at 48 in Figs. 2 A and 4.
  • the basic output of the pulse generator 36 is shown in Fig. 2B.
  • the train of pulses comprises a plurality of so-called biphasic, rectangular impulses.
  • Each biphasic rectangular impulse has a rectangular positive half pulse 50, and a rectangular negative half pulse 52 immediately following the positive half pulse, so that the impulse width is determined by the width of 50 plus the width of 52.
  • the biphasic impulse 50, 52 o Fig. 2B. is then followed by an interval and is then followed by a second biphasic impulse indicated as 50', 52' in Fig. 2B.
  • the distance between sequential positive half waves 50, 50' of the biphasic pulses determines the pulse repetition frequency of the signal.
  • the voltage applied to the electrodes 40 is zero, i.e. the same as the voltage at the neutral electrode 42, so that no stimulation of the patient occurs.
  • This zero voltage is indicated by 54 in . the diagram of Fig. 2B. It will be noted that instead of applying voltages to the electrodes, currents can be applied to them in which case the references above to voltages should be regarded as references to currents.
  • each train of biphasic rectangular pulses is timed to start at the end of the T-phase of the ECG, i.e. at points 56 in the diagram of Fig. 2C which shows an enlarged section of an ECG trace with the impulse trains 44 superimposed on it.
  • the pulse repetition frequency of the biphasic rectangular pulses of each train is selected so that ten such pulses occur within the train duration.
  • the train duration is usually selected to correspond to a time equivalent to from 10 to 25 % of , the TQ diastole duration of a human being undergoing treatment.
  • a typical value of the train duration will amount to 10 % of the total duration of the heart beat, i.e. the R-R distance.
  • the pulse repetition frequency delivered by the pulse generator 36 would, in this example, be ten pulses in one tenth of the duration of a heart beat, which might typically be equivalent to 1 second, thus resulting in a pulse repetition frequency of the individual pulses of the trains of 100 Hz.
  • the amplitude of the output signal of the pulse generator 36 i.e. as applied to the electrodes 40, can vary from a positive amplitude 50 of plus 20 V to a negative amplitude 52 of minus 20 V.
  • the relationship between the pulse width and the pulse interval of each train of pulses determines the total energy input into the muscles stimulated via the electrodes 40, 42. While a ratio of 1: 10 has been found effective, this ratio can be varied substantially and indeed an interval is not absolutely essential. Generally speaking, with all patients a threshold is reached, depending on the pulse amplitude and the ratio of the pulse width to the interval, at which involuntary contractions of the muscle are apparent to a trained observer and the apparatus will usually be operated with amplitudes and ratios of the pulse width to pulse interval at levels at which apparent involuntary muscular contractions do occur, i.e. above the threshold value.
  • biphasic rectangular pulses of the kind described above have been found to be satisfactory and currently represent the preferred type of pulses, they are by no means the only possibility.
  • the pulses delivered by the pulse generator will be biphasic in the sense that they have some positive going signal component and some negative going signal component.
  • the negative half wave is of the same size and shape as the positive half wave.
  • the positive half wave could be of different amplitude and width from the amplitude and width of the negative half wave.
  • the pulses to be rectangular pulses. They could be sinusoidal or they could have some other shape if desired.
  • a preferred embodiment of the invention provides the operator 46 with seven different parameters which he can set during the treatment of a patient.
  • the first of these is the delay or impulse delay, which, as shown in Fig. 2C, is the time difference between the Q wave end of a QRS heart signal and the effective start of the impulses, i.e. the start of the train or burst of impulses which commences at the end of the T-wave.
  • the operator 46 has the possibility of adjusting this delay at 48, for example, by varying a potentiometer which determines the delay. This is an extremely important adjustment in the apparatus of Fig. 2A and 4 for the following reason:
  • the effect of the pulses is to unload the heart. This manifests itself by a reduction of the pulse rate, i.e. of the frequency of the heart beat. This means that the time between successive R peaks of the ECG trace increases. Not only does R-R increase, but the distance from Q to the end of the T wave also increases because it stands in a known relationship to the time interval R-R. Thus, if the delay were fixed, the start of the train of pulses 44 would not always coincide with the end of the T-wave due to the change in the pulse rate. Accordingly, with the apparatus of Fig.
  • the operator 46 is able to adjust the delay at 48 to ensure that the train of pulses is always initiated at the end of the T-wave.
  • the patient's pulse rate it is entirely usual when using the apparatus of the present invention, for the patient's pulse rate to drop from, say, 72 to 62 over a ten minute period, so that the operator 46 has plenty of time to effect the necessary adjustment.
  • the duration of the train of pulses applied to the patient after the end of each T-wave is defined as the time between the start and the end of the impulses within a train or burst of impulses. This possibility of variation is indicated in Fig. 4 by the reference numeral 58.
  • the train itself is the package of electric impulses which are repeated one after the other for the time defined by the duration of the train.
  • the number, of electric impulses in each, train can be varied by varying the o ⁇ tput frequency of the pulse generator, i.e. the pulse repetition frequency of the pulses in each train of pulses, i.e. the number of pulses that are repeated per second if the train of pulses were to be one second long.
  • the duration of the train determines how long the stimulation with a given frequency is repeated, i.e. how many impulses are effectively delivered within one heart cycle. This frequency and the duration of the train can be varied by the operator 46 at the input 60 in the example of Fig. 2A and Fig. 4.
  • the other variable which can be readily changed by the operator 46 in the embodiment of Figs. 2A and 4 is the amplitude of the biphasic rectangular impulses, i.e. the maximum difference between the peak value of the positive half cycle 50 and the peak value of the negative half cycle 52, as shown in Fig. 2B. This possibility of adjustment is indicated at 62 in Fig. 4.
  • the amplitude is normally measured as a potential difference in volts.
  • Figs. 2 A and 4 there are three further parameters of the pulses which are fixed, i.e. cannot in this embodiment be varied by the operator 46.
  • the first of these parameters is pulse width, i.e. the time before the start and end of an electric impulse, as shown in Fig. 2B.
  • the pulse width is selected in the example of Figs. 2A and 4, so that the inters val at a pulse repetition frequency of 100 Hz is ten times as long as the pulse width. That is to say by fixing the pulse width the interval will automatically vary as the pulse repetition frequency is varied.
  • the pulse width is made variable, as it is in some other embodiments, then varying the pulse width automatically results in the interval shown in Fig. 2B varying, on the assumption that the repetition frequency of the pulses of the train of pulses does " . not change.
  • Box 64 in Fig. 4 relateis to the input at which the fixed value of the pulse width is selected.
  • the further boxes 66, 68 in Fig. 4 represent two further parameters of the output of the pulse generator, which in the apparatus of Fig. 2A and Fig. 4 are fixed and not readily variable by the operator 46.
  • Box 66 relates to the impulse form, i.e. the geometric form of the electric impulse resulting when the amplitude of the electric impulse is displayed over the entire impulse width. In the present example this is a biphasic rectangular pulse but it could have different shapes, for example sinusoidal or saw-toothed.
  • Box 68 refers to the possibility of changing the impulse mode which relates to the alternating mode of how impulse forms are repeated between electric positive and electric negative phase of impulses.
  • the impulse mode is clearly biphasic, with positive and negative, but otherwise identical electric impulses alternating one after the other. This mode switch would, however, allow the operator to select some other mode, for example two positive half pulses followed by one negative half pulse.
  • the electrode 42 is a neutral electrode and it is only necessary to provide one such neutral electrode.
  • more than one neutral electrode can be used when different areas of the body are treated, in order to allow a neutral electrode to be in the vicinity of each active electrode or each group of active electrodes.
  • the stimulating impulses to the different active electrodes 40 in sequence it is possible to ensure that the muscle groups affected by the applied impulses do not become tired.
  • the minimum number of active electrodes for sequencing is two.
  • Fig. 4 also shows with a series of boxes how the stimulation input to the patient from the pulse generator affects the body.
  • Box 70 indicates that the stimulation can be direct stimulation or neuromuscular stimulation which is more usual. As noted above, the stimulation aspect will be described later in more detail.
  • Box 72 shows that the stimulation can be applied either to skeletal muscles or to smooth muscles.
  • the effect of applying the stimulation to skeletal or smooth muscles is in both cases to produce a pressure pulsation in a local blood vessel of the peripheral vascular system indicated by the box 74.
  • This local pressure fluctuation propagates via the blood, essentially an incompressible liquid indicated by box 76, to the heart indicated by box 78.
  • the pulses are timed correctly and applied in accordance with the teaching of the present invention, then they have been found to have a significant effect in reducing the heart load, which itself has an effect on the body of the patient indicated by box 80. This effect is picked up by the electrodes 30 of the electrocardioscope.
  • a signal corresponding to the pulse rate for example the R-R signal, is then passed on to the pulse generator and triggers the generation of the biphasic rectangular pulses of the individual pulse . , . . trains.
  • the ECG wave form 82 is shown on the display 34 of the electrocardioscope as is the output signal of the pulse generator, as shown by the lines 82 and 84 in Fig. 4.
  • the operator 46 has the ability to vary the impulse delay to ensure that each train of pulses starts at the end of the T-wave of the electrocardiogram or at the position deemed optimal in a particular case.
  • the operator 46 is able to see, by observing the display 34, how the patient's heart rate drops in response to the treatment and is able to vary the impulse delay accordingly.
  • the impulse delay is conceptually considered as measured from the end of the Q-wave, it can be measured from another datum if required. It is in fact simpler to measure the impulse delay from the R peaks because these are larger signals which also occur at clearly defined times.
  • Fig. 3 gives a graphic representation of the effect of the treatment with the method and apparatus of the invention.
  • the topmost curve 86 shows several peaks of an ECG wave form and is divided basically into three sections A, B and C.
  • Section A shows a patient's cardiac rhythm in a normal situation, i.e. without stimulation.
  • Section B shows the cardiac rhythm for the same patient at the start of stimulation and section C shows the cardiac rhythm during continued stimulation.
  • This division into sections A, B, C also applies to the further curves 88 and 90.
  • section B shows the first train of impulses 44 which starts after the end of the T-wave and lasts for about 15 % of the T-Q path. This same wave form repeats in phase C and continues repeating until the stimulation is terminated.
  • Curve.88 shows the modulation of the muscular power resulting from the trains of electrical impulses such as 44.
  • phase A of line 88 there is no stimulation and accordingly the line is a straight line.
  • the first stimulation occurs in the section B and results in a stimulation of a muscle which affects the peripheral vascular system.
  • the muscle contraction 3 starts at the start of the train of pulses 44 and tends to reach its maximum contraction at the end of the train of pulses and then relaxes over a time period slightly longer than the train duration.
  • the train of pulses 44 contains a plurality of stimulating electrical impulses but results in a simple muscular contraction. This muscular contraction 3 produces a pressure pulsation in the patient's peripheral vascular system which propagates back to the patient's heart.
  • the curve 90 which is in fact a composite curve showing the pressure in the aorta and the left ventricular pressure.
  • the left ventricular pressure starts from a base line value 92 and increases smoothly into a rounded peak 94, which has a value above the base line value 92 from the start of the Q wave until just after the end of the T-wave.
  • a curve 96 for the pressure in the aorta is superimposed on this curve.
  • valves 20, 22 in Fig. 1C open and the pressure in the left ventricle is communicated directly into the aorta so that the pressure in the aorta rises at the same rate and with the same value as the pressure in the left ventricle until the end of the T-wave is reached, i.e. until the point.100. in Fig. 3, where the valves 20, 22 close, again and the pressure in the aorta gradually sinks as the blood in it moves through the arteries of the human body.
  • the valves 20, 22 open again and the cycle repeats.
  • the effect of the muscular contraction is to modulate the pressure in the aorta by a pressure wave traveling back to the aorta, from the peripheral blood vessel pulsation induced by the muscle contraction, so that in phase B it is slightly higher - shown as a visible hump - in the region labeled 2 than the corresponding value in phase A of curve 96.
  • the pressure in the aorta sinks to lower values than were present in the corresponding section of the pressure curve in phase A.
  • the hump 2 in the pressure in the aorta in diastole results in increased coronary circulation, i.e. more blood and more oxygen is being supplied to the heart muscles, resulting in more energy being made available to the heart.
  • This causes the pulse rate to reduce so that the duration of each heart beat increases from the value a before stimulation by the amount b to the value a + b after prolonged stimulation.
  • the typical measured reduction with various probates is about 10 pulses per minute in the rest mode, for example 70 down to 60, or up to 30 or more at a high pulse rate, for example from 140 to 110, because of an increase of the DPTI/TTI ratio (diastolic blood pressure time index/ time tension index).
  • the reduction indicated by 4 from the peak value 94 in phase A to the peak value 94" in the phase C represents a fall in the systolic pressure in the left ventricle and thus reducing left ventricular wall tension.
  • the pre-systolic blood pressure i.e. the pressure at the points 98, 98', 98" in Fig. 3 seems to reduce by about -5 mm Hg for a probate with normal blood pressure of 120/60. Extremely beneficial is the fact that with patients with blood pressure which is too high the reduction is far more pronounced, although the reduction in the heart rate for such patients tends to be less than for normal patients.
  • cardioresonance electrostimulation of the invention not only results in a lower systolic pressure but also a steeper pressure increase in the systole, which can also be seen from curve 90 in phase C of Fig. 3.
  • DPTI increases by some +10 to 15 % depending on probates resulting from the hump in the blood pres- sure increase in diastole, reduced heart pulse rate and corrected by the difference from reduced pre-systolic blood pressure, assuming probates with normal blood pressure.
  • TTI decreases by some 4 to 5 %, resulting from lower pre-systolic blood pressure corrected by the steeper pressure increase in systole (as shown at 7 in Fig. 3).
  • the DPTI / TTI ratio consequently increases by some 15 to 20 % depending on probates for those having normal blood pressure.
  • the typical heart load reduction is some 10 to 25 % or more depending on the probates and their physical condition, which results from lower heart pulse rate and reduced systolic blood pressure and lower presystolic pressure.
  • myocardial contractivity is improved, coronary blood circulation increased and ischemia reduced.
  • the patient 124 is subjected not to stimulating electrical signals, but rather to acoustic waves or signals generated via a loudspeaker 150.
  • the loudspeaker is triggered or energized via the pulse generator 136 incorporated into the electrocardioscope 128 as before.
  • the pulse generator 136 acts on the loudspeaker 150 to generate acoustic pulsations as shown in box 152 which are applied to the body 162 of the patient 124.
  • These pressure pulsations are perceived by the brain 164, which then acts on the patient's nervous system 166, which in turn leads to smooth muscle contraction, as shown in box 168, which in turn produces blood vessel pulsation 170.
  • the pressure pulsation is transmitted via the patient's blood 172 to the patient's heart 174 where it affects the patient's heart pulse rate sche- matically indicated in box 178.
  • the effect on the heart causes the heart to have an effect on the patient's vascular system, i.e. on his body, indicated schematically at 176. More specifically, it affects the patient's pulse rate at the sensing location, as indicated by box 178, and the patient's blood pressure, as indicated by box 180.
  • the heart pulse rate is passed on to ensure that the acoustic pulsations are generated or timed correctly with respect to the end of the T-waye.
  • the box labeled 200 schematically represents the patient's body with diagrams representing a smooth or skeletal muscle 202, the patient's heart 204 and the patient's ears 206.
  • the box 208 represents a heart rhythm sensor which can be of any known kind, i.e. can for example be a electrocardiograph or a sensor of the "Polar" type or an ear sensor or similar.
  • the heart rhythm sensor 208 produces a signal corresponding to the signal shown in Fig. 1A or at least two regularly repeating characteristic elements of the signal such as the R-R peaks, although these peaks may in turn be represented simply by rectangular ' pulses.
  • the signal from the heart rhythm sensor 208 passes into the stimulator 210 which basically corresponds to a combination of the pulse generator 36 of Fig. 4 with the pulse generator 136 of Figs. 5A and B.
  • the stimulator or pulse generator 210 has two outputs. Firstly, ah electrical output by which stimulating electrical- signals are applied to electrodes, such as 40 and 42, which transmit the stimulating electrical signals to the selected smooth or skeletal muscle 202 of the patient's body. Again, one of these electrodes is a neutral electrode and the other an active electrode in precisely the way as described previously in relation to the earlier application.
  • the second output of the stimulator 210 is also an electrical signal which, in this case, is passed to an acoustic generator, for example to the loudspeaker 150 of Fig.
  • the electrical energization of the loudspeaker leads to acoustic pulsation and acoustic stimulating signals indicated schematically at 212 being directed onto the patient's body 200 and particularly to the patient's ears 206.
  • a loudspeaker the patient could be equipped with a pair of headphones (not shown) which directly transmit sound to the patient's ears 206.
  • the electrical signals fed to the loudspeaker or to the earphones are initiated at the same time as the electrical signals which are sent to the active electrode or electrodes and they have a duration equal either to the duration of the signals sent to the active electrode or electrodes or a duration corresponding to the associated duration of the contractual movement of the muscle as indicated by MP in Fig. 3. It is preferred for the electrical signals transmitted to the loudspeaker to commence at the end of the T-wave as illustrated in Fig. 6B and' this also applies to the signals sent to the active electrode or electrodes.
  • the preferred duration for the electrical signals sent to the active electrode or electrodes is equivalent to 10 to 25 % of the TQ length of the associated heart wave, with 15 % being particularly preferred.
  • the start of the electrical stimulation signal to the electrode or electrodes may be titt ⁇ ed to commence just before the end of the T-wave, for example by an amount equivalent to 5 % of the R-R-path of the relevant heart wave and it is also possible for the start of the electrical stimulating signal to the electrode to be transmitted to the electrode or electrodes somewhat after the end of the associated T-wave.
  • the starting times of the electrical signals sent to the sound generator may coincide with the starting times of the electrical signals sent to the active electrode or electrodes, this is not essential and differences in timing are possible.
  • the signals sent to the sound generator should preferably be in counterpulsation to the patient's heart 204.
  • Fig. 6C The effect of the combined acoustic and electrical stimulation of the patient 200 is shown in Fig. 6C. It can be seen that the patient's heart rate reduces from an initial value of 100 %, corresponding in a healthy person to a frequency of e.g. 72 beats per minute, to a lower level of for example 80 % of the patient's normal heartbeat, with the reduction in heartbeat following an asymptotic curve 214 and the reduction in heartbeat being achieved over a period of about 20 minutes.
  • Figs. 7 A and 7B there is shown an apparatus similar to that of Figs. 6A to C, but with a significant difference which will be described shortly. Items of the apparatus and organs of the patient common to those of the first embodiment of Figs. 6A to C are designated in Figs. 7A and B with the same reference numerals and the description given above will be understood to apply to them. It will be seen that the stimulation of the patient via the electrical stimulating signals supplied to the electrodes 40, 42 is precisely the same as in the preceding embodiment. In this respect, the stimulator 214 is identical to the stimulator 210.
  • the stimulator 214 differs from the stimulator 210 with respect to the acoustic stimulation of the patient 200 via the loudspeaker 150 (or earphones) and the sound waves 212.
  • the stimulator has an output line 216 which passes on the signal from the heart rate sensor 208 to a circuit 218 which produces an average initial heart rhythm when the apparatus is first switched on.
  • This initial average heart rhythm is passed, as shown ' by the arrow 220, to a function generator 222 which produces an artificial heart rhythm signal which progressively reduces from a 100 % level set by the circuit of block 218 to a lower level corresponding, for example, to 75 % of the initial value over a period of time, which may, for example, be of the order of 20 minutes.
  • the output of the function generator 222 is thus an artificial heart rhythm indicated by the box 224 and this is used to trigger an electrical signal generator 226 which supplies electrical signals to the loudspeaker 150 (or the corresponding earphones).
  • This signal can, for example, be a signal in accordance with any one of Figs. 9A to G.
  • Fig. 7B shows the function generated by the function generator 222 to a larger scale. It can be seen that the function generator has variable parameters with enable the progressive reduction of the heart rate from the 100 % level to the selected lower level to be varied as a function of time. Thus; 5 it is possible ' to' vary the" shape of the curve (acoustic signal curve) determining the reduction, in particular the time period which elapses between the initial starting of the function generator and the attainment of the lower artificial heart rate value and the percentage reduction selected can also be varied.
  • Fig. 7B shows a curve 1 representing the reduction in the patients heart rate with electrical stimulation but without acoustic stimulation whereas curve 2 shows the faster reduction obtained with both types of stimulation acting simultaneously.
  • the circuit 218 can be dispensed with and the function generator 212 can be provided with an input which the patient, or a person administering the treatment, can activate to input an initial value for the artificial heart rhythm. This could, for example, simply be determined by taking the patient's pulse in any known manner.
  • such an input can be dispensed with altogether and the function generator can simply be designed so that when it is switched on, it starts at an appropriate frequency, for example 72 beats per minute. It may, however, by preferable to start at a higher value to facilitate dragging down the heart rate of a patient having a higher rest pulse rate.
  • the box 224 represents an artificial heart rhyth .
  • This can, for example, simply be a digital signal having rectangular pulses or spikes simulating the R points of an electrocardigraph and clearly the period between successive R points directly represents the frequency of the artificial heart rhythm.
  • the signal generator 226 for generating the electrical signals which energize the acoustic generator 150 is designed so that the initiation of the pulses to the acoustic generator takes place at a time corresponding to the end of the T-wave of the artificial heart rhythm. Because the artificial heart rhythm does not necessarily include a T-wave, the position of the effective end of the T-wave can be calculated from the respective R-R-path using the known Bazett relationship.
  • the timing and duration of the electrical energizing signals to the acoustic generator 150 can thus be set precisely as in Fig. 6A, but now related to the artificial heart rhythm rather than to the actual heart rhythm. Although it might initially appear that there is no meaningful reason to time the acoustic pulses in the same way as in the embodiment of Fig. 6A, there is in fact a reason for doing so.
  • the aim of the present embodiment is to cause the patient's heart to slow down and the ideal situation would be for the patient's heart to actually slow down to the lower limit set by the artificial heart rhythm.
  • the signals generated via the acoustic generator will be synchronized with the electrical stimulating signals applied to the active electrode or electrodes and will also be in counterpulsation to the patient's actual heart rhythm.
  • the idea is thus that by applying the same timing, the synchronization of the patient's heart with the artificial heart rhythm will be facilitated.
  • Figs. 8A to 8C there is shown an apparatus in accordance with the third aspect of the present invention.
  • the same reference numerals are again used to describe components of the apparatus and organs of the patient as have been used in connection with Figs. 6A to C and 7A to 7B.
  • the description given of these elements and features also applies to the embodiment of Figs. 8A to C.
  • both the electrical stimulation signals and the acoustic stimulation signals are determined from an artificial heart rhythm and are applied, initially at least asynchronously, to the patient's actual heart rhythm.
  • box 218 represents an input which can receive an initial heart rhythm signal.
  • This can either be an arbitrary selected value as described above in connection with Fig. 7A, or it can be a value derived from the patient's actual rest pulse rate at the start of the treatment as measured by any means.
  • This input thus determines the 100 % frequency of the artificial heart rhythm generated by the function generator 222.
  • the function generator is adapted to lower the artificial heart rhythm progressively over a period of time from say the 100 % level to a 75 % level and the output of the function generator 222, i.e. the artificial heart rhythm, is present in the box labeled 224.
  • the parameters of the function generator for example the shape of curve, the time taken to produce the artificial drop in heart rate and the level set for the lowest artificial heart rate, can be varied by the operator at will.
  • the artificial heart rhythm present at the box 224 is passed to a stimulator 210 which can be designed exactly as the stimulator 210 in Fig. 6A, since it provides both electrical signals to the electrodes 40, 42 and the electrical signals to the acoustic sound generator 150, be it a loudspeaker or earphones.
  • the timing and duration of the electrical stimulating signals to the active electrode or electrodes and of the electrical signals to the aicotis ' tic a 'generator can be selected precisely in the •• • ⁇ manner taught with reference to Fig. 6A, but are related here not to the patient's actual heart rhythm. However, they are related here to the artificial heart rhythm.
  • the aim is to exploit the phenomenon of bio-feedback, so that the patient's actual heart rate drops to a level set by the artificial heart rhythm.
  • the patient's heart rate should preferably drop to an actual heart rate corresponding to the lowest level of the artificial heart rhythm, however, this is not essential and it may simply reduce to a lower level which still differs from the lowest rate set by artificial heart rhythm.
  • the aim is for the principle of bio-feedback to lead to a situation where the patient's body behaves in relation to the stimulating signals such that these are applied in counterpulsation to the patient's actual heart rhythm. In this case there is apparently no merit in delaying the pulses produces by the stimulator 210 by any specific amount in relation to the R-R signal from box 224 although the delay - if any - should be constant.
  • the patient's heart should adapt, so that it operates in counterpulsation. This admittedly seems rather surprising at first, however, it can be understood with reference to potential energy. It is a known principle in physics that systems tend towards stable operating situations associated with potential energy minimums. The lowest heart load can also be equated with a local energy minimum and thus the present aspect of the present invention is based on the premise that the patient's heart rhythm will tend to adopt a state in relation to the stimulating signals which corresponds to such a minimum, i.e. a situation in which the heart load is at a minimum and the patient's heart is operating in counterpulsation to the stimulating signals.
  • Fig. 8B indicates how the patient's actual heart rate gradually moves into synchronism with the artificial heart rate over the course of time when the invention is operating in the desired manner.
  • Figs. 9A to G there can be seen various possible shapes for the electrical signals applied to the acoustic generator and thus for the corresponding acoustic signals that are generated.
  • an artificial heart rhythm is applied to the acoustic generator, i.e. a signal which can be obtained by recording the heart rhythm from a patient's heart and applying it in counterpulsation out of phase to the patient's actual heart rhythm.
  • the curve 230 represents the patient's actual heart rhythm
  • the curve 232 represents the acoustic heart signal applied in counterpulsation.
  • the acoustic heart signals applied in counterpulsation has the same frequency mix and distribution as the " recorded heart signal.
  • Fig. 9B shows that the acoustic signal may be a sequence of pulse bursts, e.g. from a buzzer, each pulse burst consisting of a single sound frequency. In the case of Fig. 9B, the pulse bursts take place against a zero background.
  • Fig. 9C shows a pulse burst signal similar to that of Fig. 9B, but in this case with a constant background signal level, for example at a higher frequency or in the form of white noise with a wide spread of frequencies.
  • Fig. 9D again shows a signal similar to that of Fig. 9B, but in this case the pulse burst is against a fluctuating background, which can again be a background at a different frequency or a white noise background.
  • Fig. 9E shows a situation similar to that of Fig.9B, but here each pulse burst itself comprises a mix:' of frequencies, here against a zero background.
  • Figs. 9F and 9G show the same pulse burst as Fig. 9E, but against backgrounds corresponding to those of Figs. 9C and 9D.
  • the programmable function generator automatically reduces this average heart rate from the 100 % set value of 72 bpm at the start in small steps to a stable value, say a typical value of 75 % of the value of the set start value (- 54 bpm) within the first 20 min. of stimulation.
  • a stable value say a typical value of 75 % of the value of the set start value (- 54 bpm) within the first 20 min. of stimulation.
  • the time to reach this stable value, the stable value and the mathematical function of how to reduce this artificial heart rate to achieve asymptotically a stable value can be freely programmed.
  • the heart rate calculated by this function generator is called the "stimulation heart rate"
  • a rhythm generator produces a periodic impulse, e.g. a small rectangular impulse (artificial R-R peak) at a rate corresponding to the "stimulation heart rate" (e.g. the 100 % heart rate reducing with time to 75 %).
  • This periodic impulse can be similar to the one emitted' by the Polar heart rate monitor. > *
  • Stimulation is now started at 100 %heart rate (example 72 bpm) and it is proportional to the "stimulation heart rate" being produced by this artificial heart rhythm generator and reducing with time according to the function generator down to 75 %. Stimulation is done with the same parameters as from the cardiosynchronized one, i.e. with a delay (after this rectangular impulse from the pulse rhythm generator, (possibly delay offset), duration, frequency and amplitude, width, form of impulse, mode of impulse. Because stimulation is asynchronous, not synchronized with heart beat, there will be a wrong timing and to a certain degree also the effective heart rate and the "stimulation heart rate will not correspond exactly, when compared to the synchronized Cardioresonance method.
  • the stimulator delivers an acoustic signal synchronized to the
  • the acoustic signal can be any sound, rhythm such as metronome, music with defined pronounced rhythm (e.g. a music with a repeated beat at a given frequency) or the real sound of a beating heart or part of it.
  • the acoustic signal can be transferred to the human body via any method e.g. loudspeaker to work on entire body or headphones or a single earphone to act only on ear.
  • the stimulator automatically registers the effective heart rate measured after an adjustable time from the start of the unit arid calculates an average (one or more heart rates in rest mode). This calculated average rest heart rate is now automatically set as the 1OO % value (for example 72 bpm). This heart rate is called the "acoustic heart rate"
  • the time to reach this stable value, the; stable value and the mathematical function of how to reduce this artificial heart rate to achieve asymptotically a stable value can be freely programmed.
  • a rhythm generator will produce a rhythm, a periodic impulse, e.g. a small rectangular impulse (artificial R-R peak) at a rate corresponding to the "acoustic heart rate"(e.g. the 100 % heart rate reducing with time to 75 %).
  • This periodic impulse can be similar to the one emitted by the Polar heart rate monitor.
  • the acoustic signal can be any sound, rhythm such as metronome, music with defined pronounced rhythm (e.g. a music with a repeated beat at a given frequency) or the real sound of a beating heart or part of it.
  • the acoustic signal can be transferred to the human body via any method e.g. loudspeaker to work on entire body or earphones to act only on ear.
  • Bio-feedback efficiency may depend on individuals and their capability to relax, to let go. Intensive preoccupation keeping the brain alert or highly emotional thoughts may reduce the effectiveness of such a bio-feedback system.
  • such an acoustic bio-feedback system will benefit from being applied with headphones (to shield against other noises) in a fully relaxing environment, such as combined with soft lights, all contributing to a relaxed atmosphere, but this is not a precondition for the working of the invention.
  • the asynchronous way demands two bio-feedback steps at the same time, reducing the heart rate and secondly, adjustment of the timing in such a way, that the heart places itself in simpulsation to the counterpul- sating stimulation and muscle contraction.

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Abstract

Appareil et procédé servant à traiter un mammifère ou autre organisme vivant ayant un coeur présentant un rythme cardiaque à phases alternées de systole et de diastole, un système vasculaire périphérique et une pression systolique résultant du fonctionnement du coeur. Ledit appareil comporte un détecteur de rythme cardiaque, un générateur d'impulsions destiné à produire des signaux de stimulation électrique synchronisés avec le rythme cardiaque et réglés pour se produire pendant les phases de diastole, au moins des première et deuxième électrodes destinées à appliquer les signaux de stimulation électrique à un ou plusieurs muscles du squelette ou lisses associés au système vasculaire périphérique, et un générateur de son destiné à produire des signaux acoustiques à fréquence de répétition d'impulsions correspondant à un rythme cardiaque. Le rythme cardiaque auquel correspond la fréquence de répétition d'impulsions est soit le rythme cardiaque détecté par le détecteur de rythme cardiaque, soit un rythme cardiaque artificiel qui est progressivement abaissé d'un rythme cardiaque initial à un rythme cardiaque plus bas. Dans un mode de réalisation dit asynchrone, les signaux de stimulation électrique sont également réglés temporellement en fonction du rythme cardiaque artificiel.
PCT/EP2002/001779 2001-02-20 2002-02-20 Appareil servant a traiter un organisme vivant pour parvenir a une reduction de la sollicitation cardiaque et procede permettant d'obtenir une reduction de la sollicitation cardiaque WO2002066112A1 (fr)

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1529550A1 (fr) * 2003-11-07 2005-05-11 Coral Licensing International Ltd. Appareil électrothérapeutique
CN106512225A (zh) * 2016-10-10 2017-03-22 遵义医学院附属医院 一种神经内科康复辅助治疗刺激装置

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GB1359005A (en) 1970-08-25 1974-07-03 Leuner H Relaxation therapy apparatus
US4541417A (en) * 1982-06-07 1985-09-17 Krikorian Paul P Coronary augmenter
US5267942A (en) * 1992-04-20 1993-12-07 Utah State University Foundation Method for influencing physiological processes through physiologically interactive stimuli
WO1998005379A1 (fr) * 1996-08-01 1998-02-12 Chou Ones C Appareil et procede de guerison et d'amelioration du bien-etre du corps humain
EP1040847A1 (fr) * 1997-11-28 2000-10-04 Masayuki Matsuura Methode de therapie ondulatoire et appareil afferent
EP1078649A1 (fr) 1999-08-20 2001-02-28 CardioRest Ltd. Dispositif de traitement d'un organisme vivant pour réduire la charge cardiaque

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1359005A (en) 1970-08-25 1974-07-03 Leuner H Relaxation therapy apparatus
US4541417A (en) * 1982-06-07 1985-09-17 Krikorian Paul P Coronary augmenter
US5267942A (en) * 1992-04-20 1993-12-07 Utah State University Foundation Method for influencing physiological processes through physiologically interactive stimuli
WO1998005379A1 (fr) * 1996-08-01 1998-02-12 Chou Ones C Appareil et procede de guerison et d'amelioration du bien-etre du corps humain
EP1040847A1 (fr) * 1997-11-28 2000-10-04 Masayuki Matsuura Methode de therapie ondulatoire et appareil afferent
EP1078649A1 (fr) 1999-08-20 2001-02-28 CardioRest Ltd. Dispositif de traitement d'un organisme vivant pour réduire la charge cardiaque
WO2001013990A1 (fr) 1999-08-20 2001-03-01 Cardiorest International Ltd. Procede de traitement d'un organisme vivant pour obtenir une baisse du travail cardiaque, et dispositif servant a mettre en oeuvre ledit procede

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1529550A1 (fr) * 2003-11-07 2005-05-11 Coral Licensing International Ltd. Appareil électrothérapeutique
CN106512225A (zh) * 2016-10-10 2017-03-22 遵义医学院附属医院 一种神经内科康复辅助治疗刺激装置
CN106512225B (zh) * 2016-10-10 2019-01-29 遵义医学院附属医院 一种神经内科康复辅助治疗刺激装置

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