CA2333360C - Augmentation of muscle contractility by biphasic stimulation - Google Patents
Augmentation of muscle contractility by biphasic stimulation Download PDFInfo
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- CA2333360C CA2333360C CA002333360A CA2333360A CA2333360C CA 2333360 C CA2333360 C CA 2333360C CA 002333360 A CA002333360 A CA 002333360A CA 2333360 A CA2333360 A CA 2333360A CA 2333360 C CA2333360 C CA 2333360C
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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
- A61N1/02—Details
- A61N1/04—Electrodes
- A61N1/05—Electrodes for implantation or insertion into the body, e.g. heart electrode
-
- 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
- A61N1/37—Monitoring; Protecting
- A61N1/3706—Pacemaker parameters
- A61N1/3708—Pacemaker parameters for power depletion
-
- 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
- A61N1/3605—Implantable neurostimulators for stimulating central or peripheral nerve system
- A61N1/36128—Control systems
- A61N1/36146—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
-
- 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
- A61N1/3627—Heart stimulators for treating a mechanical deficiency of the heart, e.g. congestive heart failure or cardiomyopathy
Abstract
Augmentation of electrical conduction and contractility by biphasic stimulation of muscle tissue. A first stimulation phase has a first phase polarity, amplitude, and duration. The first stimulation phase, which acts a s a conditioning mechanism, is administered at no more than a maximum subthreshold amplitude. A second stimulation phase has a second polarity, amplitude, and duration. The two phases are applied sequentially. Contrary t o current thought, anodal stimulation is applied as the first stimulation phas e, followed by cathodal stimulation as the second stimulation phase. In this fashion, pulse conduction through muscle is improved, together with an increase in contractility. Furthermore, this mode of biphasic stimulation reduces the electrical energy required to elicit contraction. In addition, t he conditioning first stimulation phase decreases the stimulation threshold by reducing the amount of electrical current required for the second stimulatio n phase to elicit contraction. The muscle tissue encompassed by the present invention includes skeletal (striated) muscle, cardiac muscle, and smooth muscle.
Description
AUGMENTATION OF MUSCLE CONTRACTILITY BY BIPHASIC STIMULATION
FIELD OF THE INVENTION
This invention relates generally to a method for the stimulation of muscle tissue. In particular, this invention relates to a method for stimulation of muscle tissue with biphasic waveforms that reduce the electrical energy required to elicit contraction.
BACKGROUND OF TH8 INV$NTION
The function of the cardiovascular system is vital for survival. Through blood circulation, body tissues obtain necessary nutrients and oxygen, and discard waste substances. In the absence of circulation, cells begin to undergo irreversible changes that lead to death. The 'muscular contractions of the heart are the driving force behind circulation.
In cardiac muscle, the muscle fibers are interconnected in branching networks that spread in all directions through the heart. When any portion of this net is stimulated, a depolarization wave passes to all of its parts and the entire structure contracts as a unit. Before a muscle fiber can be stimulated to contract, its membrane must be polarized. A muscle fiber generally remains polarized until it is stimulated by some change in its environment. A membrane can be stimulated electrically, chemically, mechanically or by z 1 temperature change. The minimal stimulation strength needed to elicit a contraction is 2 known as the threshold stimulus. The maximum stimulation amplitude that may be 3 administered without eliciting a contraction is the maximum subthreshold amplitude.
FIELD OF THE INVENTION
This invention relates generally to a method for the stimulation of muscle tissue. In particular, this invention relates to a method for stimulation of muscle tissue with biphasic waveforms that reduce the electrical energy required to elicit contraction.
BACKGROUND OF TH8 INV$NTION
The function of the cardiovascular system is vital for survival. Through blood circulation, body tissues obtain necessary nutrients and oxygen, and discard waste substances. In the absence of circulation, cells begin to undergo irreversible changes that lead to death. The 'muscular contractions of the heart are the driving force behind circulation.
In cardiac muscle, the muscle fibers are interconnected in branching networks that spread in all directions through the heart. When any portion of this net is stimulated, a depolarization wave passes to all of its parts and the entire structure contracts as a unit. Before a muscle fiber can be stimulated to contract, its membrane must be polarized. A muscle fiber generally remains polarized until it is stimulated by some change in its environment. A membrane can be stimulated electrically, chemically, mechanically or by z 1 temperature change. The minimal stimulation strength needed to elicit a contraction is 2 known as the threshold stimulus. The maximum stimulation amplitude that may be 3 administered without eliciting a contraction is the maximum subthreshold amplitude.
4 Where the membrane is stimulated electrically, the impulse amplitude required to elicit a response is dependent upon a number of factors. First, is the duration of current flow.
6 Since the total charge transferred is equal to the current amplitude times the pulse duration, 7 increased stimulus duration is associated with a decrease in threshold current amplitude.
8 Second, the percentage of applied current that actually traverses the membrane varies 9 inversely with electrode size. Third, the percentage of applied current that actually traverses the membrane varies directly with the proximity of the electrode to the tissue. Fourth, the 11 impulse amplitude required to elicit a response is dependent upon the timing of stimulation 12 within the excitability cycle.
13 Throughout much of the heart are clumps and strands of specialized cardiac muscle 14 tissue. This tissue comprises the cardiac conduction system and serves to initiate and distribute depolarization waves throughout the myocardium. Any interference or block in 16 cardiac impulse conduction may cause an arrhythmia or marked change in the rate or rhythm 17 of the heart 18 Sometimes a patient suffering from a conduction disorder can be helped by an 19 artificial pacemaker. Such a device contains a small battery powered electrical stimulator.
When the artificial pacemaker is installed, electrodes are generally threaded through veins 21 into the right ventricle, or into the right atrium and right ventricle, and the stimulator is 22 planted beneath the skin in the shoulder or abdomen. The leads are planted in intimate 23 contact with the cardiac tissue. The pacemaker then transmits rhythmic electrical impulses to 24 the heart, and the myocardium responds by contracting rhythmically.
Implantable medical devices for the pacing of the heart are well known in the art and have been used in humans 26 since approximately the mid 1960s.
27 Either cathodal or anodal current may be used to stimulate the myocardium.
However 28 anodal current is thought not to be useful clinically. Cathodal current comprises electrical 29 pulses of negative polarity. This type of current depolarizes the cell membrane by discharging the membrane capacitor, and directly reduces the membrane potential toward 31 threshold level. Cathodal current, by directly reducing the resting membrane potential toward WO 99/61100 ~ PCT/US99/11376 1 threshold, has a one-half to one-third lower threshold current in late diastole than does anodal 2 current. Anodal current comprises electrical pulses of positive polarity.
The effect of anodal 3 current is to hyperpolarize the resting membrane. On sudden termination of the anodal pulse, 4 the membrane potential returns towards resting level, overshoots to threshold, and a propagated response occurs. The use of anodal current to stimulate the myocardium is 6 generally discouraged due to the higher stimulation threshold, which leads to use of a higher 7 current, resulting in a drain on the battery of an implanted device and impaired longevity.
8 Additionally, the use of anodal current for cardiac stimulation is discouraged due to the 9 suspicion that the anodal contribution to depolarization can, particularly at higher voltages, contribute to arrhythmogenesis.
11 Virtually all artificial pacemaking is done using stimulating pulses of negative 12 polarity, or in the case of bipolar systems, the cathode is closer to the myocardium than is the 13 anode. Where the use of anodal current is disclosed, it is generally as a charge of minute 14 magnitude used to dissipate residual charge on the electrode. This does not affect or condition the myocardium itself. Such a use is disclosed in U.S. Patent No.
4,543,956 to 16 Herscovici.
17 The use of a triphasic waveform has been disclosed in U.S. Patent Nos.
4,903,700 and 18 4,821,724 to Whigham et al., and U.S. Patent No. 4,343,312 to Cals et al.
Here, the first and 19 third phases have nothing to do with the myocardium per se, but are only envisioned to affect the electrode surface itself. Thus, the charge applied in these phases is of very low amplitude.
21 Lastly, biphasic stimulation is disclosed in U.S. Patent No. 4,402,322 to Duggan. The 22 goal of this disclosure is to produce voltage doubling without the need for a large capacitor in 23 the output circuit. The phases of the biphasic stimulation disclosed are of equal magnitude 24 and duration.
What is needed is an improved means for stimulating muscle tissue, wherein the 26 contraction elicited is enhanced and the damage to the tissue adjacent to the electrode is 27 diminished.
28 Enhanced myocardial function is obtained through the biphasic pacing of the present 29 invention. The combination of cathodal with anodal pulses of either a stimulating or conditioning nature, preserves the improved conduction and contractility of anodal pacing 31 while eliminating the drawback of increased stimulation threshold. The result is a 1 depolarization wave of increased propagation speed. This increased propagation speed 2 results in superior cardiac contraction leading to an improvement in blood flow. Improved 3 stimulation at a lower voltage level also results in reduction in power consumption and 4 increased life for pacemaker batteries.
As with the cardiac muscle, striated muscle may also be stimulated electrically, 6 chemically, mechanically or by temperature change. Where the muscle fiber is stimulated by 7 a motor neuron, the neuron transmits an impulse which activates all of the muscle fibers 8 within its control, that is, those muscle fibers in its motor unit.
Depolarization in one region 9 of the membrane stimulates adjacent regions to depolarize as well, resulting in a wave of depolarization traveling over the membrane in all directions away from the site of 11 stimulation. Thus. when a motor neuron transnuts an impulse, all the muscle fibers in its 12 motor unit are stimulated to contract simultaneously.
13 The minimum strength to elicit a contraction is called the threshold stimulus. Once 14 this level of stimulation has been met, the generally held belief is that increasing the level will I S not increase the contraction. Additionally, since the muscle fibers within each muscle are 16 organized into motor units, and each motor unit is controlled by a single motor netuon, all of 17 the muscle fibers in a motor unit are stimulated at the same time. However, the whole muscle 18 is controlled by many different motor routs that respond to different stimulation thresholds.
19 Thus, when a given stimulus is applied to a muscle, same motor units may respond while others may not.
21 The combination of cathodal and anodal pulses of the present invention also provides 22 improved contraction of'striated muscle where electrical muscular stimulation is indicated 23 due to neural or macular damage. Where nerve fibers have been damaged due to trauma or 24 disease, muscle fibers ui the regions supplied by the damaged nerve fiber tend to undergo atrophy and waste away. A muscle that cannot be exercised may decrease to half of its usual 26 size in a few months. Where there is no stimulation, not only will the muscle fibers decrease 27 in size, but they will become fragmented and degenerated, and replaced by connective tissue.
28 Through electrical stimulation, one may maintain muscle tone such that, upon healing or 29 regeneration of the nerve fiber, viable muscle tissue remains, and the overall regenerative process is thereby enrlanced and assisted.
31 Striated muscle stimulation can also serve to preserve the neural pathway, such that, 1 upon healing of the nerve fibers associated with the stimulated tissue, the patient 2 "remembers" how to contract that particular muscle. Enhanced striated muscle contraction is 3 obtained through the biphasic stimulation of the present invention. The combination of 4 cathodal with anodal pulses of either a stimulating or conditioning nature results in contraction of a greater number of motor units at a lower voltage level, leading to superior 6 muscle response.
Lastly, biphasic stimulation as provided by the present invention may be desirable to 8 stimulate smooth muscle tissue, such as those muscles responsible for the movements that 9 force food through the digestive tube, constrict blood vessels and empty the urinary bladder.
For example, appropriate stimulation could rectify the difficulties associated with 11 incontinence.
13 It is therefore an object of the present invention to provide improved electrical 14 stimulation of muscle tissue.
It is another object of the present invention to extend battery life of implantable 16 electrical stimulation devices.
1~ It is a further object of the present invention to obtain effective muscle stimulation at a 18 lower voltage leve 19 It is a further object of the present invention to provide improved stimulation of muscle tissue, particularly striated muscle.
21 It is a further ~biect of the present invention to provide contraction of a greater 22 number of muscle motor units at a lower voltage level.
23 It is a further object of the present invention to provide contraction of a greater 24 number of muscle motor units at a lower level of electrical current.
A method and apparatus for muscular stimulation in accordance with the present 26 invention includes the administration of biphasic stimulation to the muscle tissue, wherein 27 both cathodal and anodal pulses are administered.
2g According to a still further aspect of this invention, the stimulation is administered to 29 muscle tissue to evoke muscular response. Stimulation may be administered directly or 1 indirectly to muscle tissue, where indirect administration includes stimulation through the 2 skin. Using the present invention, lower levels of electrical energy (voltage and/or current) 3 are needed to reach the threshold stimulus, compared to conventional stimulation methods.
4 Muscle tissue that may benefit from stimulation according to the present invention include skeletal (striated) muscle, cardiac muscle, and smooth muscle.
The electronics required for the implantable stimulation devices needed to practice the 7 method of the present invention are well knownto those skilled in the art.
Current 8 implantable stimulation devices are capable of being programmed to deliver a variety of 9 pulses, including those disclosed herein. In addition, the electronics required for indirect muscle stimulation are also well known to those skilled in the art and are readily modified to 11 practice the method of the present invention.
12 The method and apparatus of the present invention comprises a first and second 13 stimulation phase, with each stimulation phase having a polarity, amplitude, shape, and 14 duration. In a preferred embodiment, the first and second phases have differing polarities. In one alternative embodiment, the two phases are of differing amplitude. In a second alternative 16 embodiment, the two phases are of differing duration. In a third alternative embodiment, the 17 first phase is in a chopped wave form. In a fourth alternative embodiment, the amplitude of 18 the first phase is rampeci. In a preferred alternative embodiment, the first phase of stimulation 19 is an anodal pulse at maximum subthreshold amplitude for a long duration, and the second phase of stimulation is a cathodal pulse of short duration and high amplitude.
It is noted that 21 the aforementioned alternative embodiments can be combined in differing fashions. It is also 22 noted that these anernative embodiments are intended to be presented by way of example 23 only, and are not !inciting.
Fig. 1 is a schematic representation of leading anodal biphasic stimulation.
26 Fig. 2 is a schematic representation of leading cathodal biphasic stimulation.
27 Fig. 3 is a schematic representation of leading anodal stimulation of low level and 28 long duration, follow;,d by conventional cathodal stimulation.
29 Fig. 4 is a schematic representation of leading anodal stimulation of ramped low level l and long duration, followed by conventional cathodal stimulation.
2 Fig. 5 is a schematic representation of leading anodal stimulation of low level and 3 short duration, administered in series, followed by conventional cathodal stimulation.
4 Fig. 6 graphs conduction velocity transverse to the fiber vs. pacing duration resulting from leading anodal biphasic pulse.
6 Fig. 7 graphs conduction velocity parallel to the fiber vs. pacing duration resulting 7 from leading anodal biphasic pulse.
6 Since the total charge transferred is equal to the current amplitude times the pulse duration, 7 increased stimulus duration is associated with a decrease in threshold current amplitude.
8 Second, the percentage of applied current that actually traverses the membrane varies 9 inversely with electrode size. Third, the percentage of applied current that actually traverses the membrane varies directly with the proximity of the electrode to the tissue. Fourth, the 11 impulse amplitude required to elicit a response is dependent upon the timing of stimulation 12 within the excitability cycle.
13 Throughout much of the heart are clumps and strands of specialized cardiac muscle 14 tissue. This tissue comprises the cardiac conduction system and serves to initiate and distribute depolarization waves throughout the myocardium. Any interference or block in 16 cardiac impulse conduction may cause an arrhythmia or marked change in the rate or rhythm 17 of the heart 18 Sometimes a patient suffering from a conduction disorder can be helped by an 19 artificial pacemaker. Such a device contains a small battery powered electrical stimulator.
When the artificial pacemaker is installed, electrodes are generally threaded through veins 21 into the right ventricle, or into the right atrium and right ventricle, and the stimulator is 22 planted beneath the skin in the shoulder or abdomen. The leads are planted in intimate 23 contact with the cardiac tissue. The pacemaker then transmits rhythmic electrical impulses to 24 the heart, and the myocardium responds by contracting rhythmically.
Implantable medical devices for the pacing of the heart are well known in the art and have been used in humans 26 since approximately the mid 1960s.
27 Either cathodal or anodal current may be used to stimulate the myocardium.
However 28 anodal current is thought not to be useful clinically. Cathodal current comprises electrical 29 pulses of negative polarity. This type of current depolarizes the cell membrane by discharging the membrane capacitor, and directly reduces the membrane potential toward 31 threshold level. Cathodal current, by directly reducing the resting membrane potential toward WO 99/61100 ~ PCT/US99/11376 1 threshold, has a one-half to one-third lower threshold current in late diastole than does anodal 2 current. Anodal current comprises electrical pulses of positive polarity.
The effect of anodal 3 current is to hyperpolarize the resting membrane. On sudden termination of the anodal pulse, 4 the membrane potential returns towards resting level, overshoots to threshold, and a propagated response occurs. The use of anodal current to stimulate the myocardium is 6 generally discouraged due to the higher stimulation threshold, which leads to use of a higher 7 current, resulting in a drain on the battery of an implanted device and impaired longevity.
8 Additionally, the use of anodal current for cardiac stimulation is discouraged due to the 9 suspicion that the anodal contribution to depolarization can, particularly at higher voltages, contribute to arrhythmogenesis.
11 Virtually all artificial pacemaking is done using stimulating pulses of negative 12 polarity, or in the case of bipolar systems, the cathode is closer to the myocardium than is the 13 anode. Where the use of anodal current is disclosed, it is generally as a charge of minute 14 magnitude used to dissipate residual charge on the electrode. This does not affect or condition the myocardium itself. Such a use is disclosed in U.S. Patent No.
4,543,956 to 16 Herscovici.
17 The use of a triphasic waveform has been disclosed in U.S. Patent Nos.
4,903,700 and 18 4,821,724 to Whigham et al., and U.S. Patent No. 4,343,312 to Cals et al.
Here, the first and 19 third phases have nothing to do with the myocardium per se, but are only envisioned to affect the electrode surface itself. Thus, the charge applied in these phases is of very low amplitude.
21 Lastly, biphasic stimulation is disclosed in U.S. Patent No. 4,402,322 to Duggan. The 22 goal of this disclosure is to produce voltage doubling without the need for a large capacitor in 23 the output circuit. The phases of the biphasic stimulation disclosed are of equal magnitude 24 and duration.
What is needed is an improved means for stimulating muscle tissue, wherein the 26 contraction elicited is enhanced and the damage to the tissue adjacent to the electrode is 27 diminished.
28 Enhanced myocardial function is obtained through the biphasic pacing of the present 29 invention. The combination of cathodal with anodal pulses of either a stimulating or conditioning nature, preserves the improved conduction and contractility of anodal pacing 31 while eliminating the drawback of increased stimulation threshold. The result is a 1 depolarization wave of increased propagation speed. This increased propagation speed 2 results in superior cardiac contraction leading to an improvement in blood flow. Improved 3 stimulation at a lower voltage level also results in reduction in power consumption and 4 increased life for pacemaker batteries.
As with the cardiac muscle, striated muscle may also be stimulated electrically, 6 chemically, mechanically or by temperature change. Where the muscle fiber is stimulated by 7 a motor neuron, the neuron transmits an impulse which activates all of the muscle fibers 8 within its control, that is, those muscle fibers in its motor unit.
Depolarization in one region 9 of the membrane stimulates adjacent regions to depolarize as well, resulting in a wave of depolarization traveling over the membrane in all directions away from the site of 11 stimulation. Thus. when a motor neuron transnuts an impulse, all the muscle fibers in its 12 motor unit are stimulated to contract simultaneously.
13 The minimum strength to elicit a contraction is called the threshold stimulus. Once 14 this level of stimulation has been met, the generally held belief is that increasing the level will I S not increase the contraction. Additionally, since the muscle fibers within each muscle are 16 organized into motor units, and each motor unit is controlled by a single motor netuon, all of 17 the muscle fibers in a motor unit are stimulated at the same time. However, the whole muscle 18 is controlled by many different motor routs that respond to different stimulation thresholds.
19 Thus, when a given stimulus is applied to a muscle, same motor units may respond while others may not.
21 The combination of cathodal and anodal pulses of the present invention also provides 22 improved contraction of'striated muscle where electrical muscular stimulation is indicated 23 due to neural or macular damage. Where nerve fibers have been damaged due to trauma or 24 disease, muscle fibers ui the regions supplied by the damaged nerve fiber tend to undergo atrophy and waste away. A muscle that cannot be exercised may decrease to half of its usual 26 size in a few months. Where there is no stimulation, not only will the muscle fibers decrease 27 in size, but they will become fragmented and degenerated, and replaced by connective tissue.
28 Through electrical stimulation, one may maintain muscle tone such that, upon healing or 29 regeneration of the nerve fiber, viable muscle tissue remains, and the overall regenerative process is thereby enrlanced and assisted.
31 Striated muscle stimulation can also serve to preserve the neural pathway, such that, 1 upon healing of the nerve fibers associated with the stimulated tissue, the patient 2 "remembers" how to contract that particular muscle. Enhanced striated muscle contraction is 3 obtained through the biphasic stimulation of the present invention. The combination of 4 cathodal with anodal pulses of either a stimulating or conditioning nature results in contraction of a greater number of motor units at a lower voltage level, leading to superior 6 muscle response.
Lastly, biphasic stimulation as provided by the present invention may be desirable to 8 stimulate smooth muscle tissue, such as those muscles responsible for the movements that 9 force food through the digestive tube, constrict blood vessels and empty the urinary bladder.
For example, appropriate stimulation could rectify the difficulties associated with 11 incontinence.
13 It is therefore an object of the present invention to provide improved electrical 14 stimulation of muscle tissue.
It is another object of the present invention to extend battery life of implantable 16 electrical stimulation devices.
1~ It is a further object of the present invention to obtain effective muscle stimulation at a 18 lower voltage leve 19 It is a further object of the present invention to provide improved stimulation of muscle tissue, particularly striated muscle.
21 It is a further ~biect of the present invention to provide contraction of a greater 22 number of muscle motor units at a lower voltage level.
23 It is a further object of the present invention to provide contraction of a greater 24 number of muscle motor units at a lower level of electrical current.
A method and apparatus for muscular stimulation in accordance with the present 26 invention includes the administration of biphasic stimulation to the muscle tissue, wherein 27 both cathodal and anodal pulses are administered.
2g According to a still further aspect of this invention, the stimulation is administered to 29 muscle tissue to evoke muscular response. Stimulation may be administered directly or 1 indirectly to muscle tissue, where indirect administration includes stimulation through the 2 skin. Using the present invention, lower levels of electrical energy (voltage and/or current) 3 are needed to reach the threshold stimulus, compared to conventional stimulation methods.
4 Muscle tissue that may benefit from stimulation according to the present invention include skeletal (striated) muscle, cardiac muscle, and smooth muscle.
The electronics required for the implantable stimulation devices needed to practice the 7 method of the present invention are well knownto those skilled in the art.
Current 8 implantable stimulation devices are capable of being programmed to deliver a variety of 9 pulses, including those disclosed herein. In addition, the electronics required for indirect muscle stimulation are also well known to those skilled in the art and are readily modified to 11 practice the method of the present invention.
12 The method and apparatus of the present invention comprises a first and second 13 stimulation phase, with each stimulation phase having a polarity, amplitude, shape, and 14 duration. In a preferred embodiment, the first and second phases have differing polarities. In one alternative embodiment, the two phases are of differing amplitude. In a second alternative 16 embodiment, the two phases are of differing duration. In a third alternative embodiment, the 17 first phase is in a chopped wave form. In a fourth alternative embodiment, the amplitude of 18 the first phase is rampeci. In a preferred alternative embodiment, the first phase of stimulation 19 is an anodal pulse at maximum subthreshold amplitude for a long duration, and the second phase of stimulation is a cathodal pulse of short duration and high amplitude.
It is noted that 21 the aforementioned alternative embodiments can be combined in differing fashions. It is also 22 noted that these anernative embodiments are intended to be presented by way of example 23 only, and are not !inciting.
Fig. 1 is a schematic representation of leading anodal biphasic stimulation.
26 Fig. 2 is a schematic representation of leading cathodal biphasic stimulation.
27 Fig. 3 is a schematic representation of leading anodal stimulation of low level and 28 long duration, follow;,d by conventional cathodal stimulation.
29 Fig. 4 is a schematic representation of leading anodal stimulation of ramped low level l and long duration, followed by conventional cathodal stimulation.
2 Fig. 5 is a schematic representation of leading anodal stimulation of low level and 3 short duration, administered in series, followed by conventional cathodal stimulation.
4 Fig. 6 graphs conduction velocity transverse to the fiber vs. pacing duration resulting from leading anodal biphasic pulse.
6 Fig. 7 graphs conduction velocity parallel to the fiber vs. pacing duration resulting 7 from leading anodal biphasic pulse.
9 The present invention relates to the biphasic electrical stimulation of muscle tissue.
Fig.
11 1 depicts biphasic electrical stimulation wherein a first stimulation phase, comprising anodal 12 stimulus 102, is administered having amplitude 104 and duration 106. This first stimulation 13 phase is immediately followed by a second stimulation phase comprising cathodal stimulation 14 108 of equal intensity and duration.
Fig. 2 depicts biphasic electrical stimulation wherein a first stimulation phase, 16 comprising cathodal stimulation 202 having amplitude 204 and duration 206, is administered.
17 This first stimulation phase is immediately followed by a second stimulation phase 18 comprising anodal stimulation 208 of equal intensity and duration.
19 Fig. 3 depicTs a preferred embodiment of the present invention wherein a first stimulation phase, comprising low level, long duration anodal stimulation 302 having 21 amplitude 304 ansl duration 306, is administered. This first stimulation phase is immediately 22 followed by a second stimulation phase comprising cathodal stimulation 308 of conventional 23 intensity and duration. In an alternative embodiment of the invention, anodal stimulation 302 24 is at maximum subthresizold amplitude. In yet another alternative embodiment of the invention, anodal stimulation 302 is less than three volts. In another alternative embodiment 26 of the invention, anodal stimulation 302 is a duration of approximately two to eight 27 milliseconds. In vet another alternative embodiment of the invention, cathodal stimulation 28 308 is of a short duration. In another alternative embodiment of the invention, cathodal 29 stimulation 308 is approximately 0.3 to 0.8 millisecond. In yet another alternative 1 embodiment of the invention, cathodal stimulation 308 is of a high amplitude. In another 2 alternative embodiment of the invention, cathodal stimulation 308 is in the approximate range 3 of three to twenty volts. In yet another alternative embodiment of the present invention, 4 cathodal stimulation 308 is of a duration less than 0.3 millisecond and at a voltage greater than twenty volts. In another alternati~~e embodiment of the present invention, cathodal 6 stimulation 308 lasts as long as 6.0 milliseconds and has a voltage as low as 200 rnillivolts.
7 In the manner disclosed by these embodiments, as well as those alterations and modifications 8 which may become obvioL~s upon the reading of this specification, a maximum membrane 9 potential without activation is achieved in the first phase of stimulation.
Fig. 4 depicts an alternative preferred embodiment of the present invention wherein a 11 first stimulation~pl~ase. comprising anodal stimulation 402, is administered over period 404 12 with rising intensity level 406. The ramp of rising intensity level 406 may be linear or non-13 linear, and the slope may vary. This anodal stimulation is immediately followed by a second 14 stimulation phase comprising cathodal stimulation 408 of conventional intensity and duration. In an alternati~~e embodiment of the invention, anodal stimulation 402 rises to a 16 maximum subthreshold amplitude. In yet another alternative embodiment of the invention, 17 anodal stimulation 402 rises to a maximum amplitude that is less than three volts. In another 18 alternative embodiment of the invention, anodal stimulation 402 is a duration of 19 approximately two to eight milliseconds. In yet another alternative embodiment of the invention. cathodal stimulation 408 l s of a short duration. In another alternative embodiment 21 of the invention. catl~odal stimulation 408 is approximately 0.3 to 0.8 millisecond. In yet 22 another alternative embodiment of the invention, cathodal stimulation 408 is of a high 23 amplitude. In another aiiernative embodiment of the invention, cathodal stimulation 408 is in 24 the approximate range of thYee to twenty volts. In yet another alternative embodiment of the present invention, cathodal :,timulation 408 is of a duration less than 0.3 milliseconds and at a 26 voltage greater than t<venty volts. In another alternative embodiment of the present invention, 27 cathodal stimulation 108 lasts as long as 6.0 milliseconds and has a voltage as low as 200 28 millivolts. In the rrarner disclosed by these embodiments, as well as those alterations and 29 modifications which may become obvious upon the reading of this specification, a maximum membrane potential without activation is achieved in the first phase of stimulation.
31 Fig. 5 depicts binhasic electrical stimulation wherein a first stimulation phase, WO 99/61100 PCr/US99/11376 _, 1 comprising series 502 of anodal pulses, is administered at amplitude 504. In one 2 embodiment, rest period 506 is of equal duration to stimulation period 508, and is 3 administered at baseline amplitude. In an alternative embodiment, rest period 506 is of a 4 differing duration than stimulation period 508 and is administered at baseline amplitude.
Rest period 506 occurs after each stim°alation period 508, with the exception that a second 6 stimulation phase, comprising cathodal stimulation 510 of conventional intensity and 7 duration, immediatel:~ follows the completion of series 502. In an alternative embodiment of 8 the invention. the total :barge transferred through series S02 of anodal stimulation is at the 9 maximum subthreshold level. In another alternative embodiment of the invention, cathodal stimulation 510 is of a Short d~wation. In yet another alternative embodiment of the invention, 11 cathodal stimulation 510 is appro~:imately 0.3 to 0.8 millisecond. In another alternative 12 embodiment of the invention, cathodal stimulation 510 is of a high amplitude. In yet another 13 alternative embodiment of the invention, cathodal stimulation 510 is in the approximate range 14 of three to twenty volts. In another alternative embodiment of the invention, cathodal stimulation 510 is of a duration less than 0.3 millisecond and at a voltage greater than twenty 16 volts. In another alternative embodiment of the present invention, cathodal stimulation 510 17 lasts as long as 6.0 milliseconds and has a voltage as low as 200 millivolts.
19 Stimulation and proYagation characteristics of the myocardium were studied in isolated hearts using pulses of differing polarities and phases. 'The experiments were earned 21 out in five isolated Langendo-tf perfused rabbit hearts. Conduction velocity on the 22 epicardium was treasured using an array of bipolar electrodes. Measurements were made 23 between six millimeters ane ni:-~e millimeters from the stimulation site.
Transmembrane 24 potential was recorded using a floating intracellular microelectrode. The following protocols were examined: mono ~zsi : cathodal pulse., monophasic anodal pulse, leading cathodal 26 biphasic pulse, anal leading anodal bzphasic pulse.
2~ Table 1 discloses the conduction speed transverse to fiber direction for each 28 stimulation protocol acuninistersd. with stimulations of three, four and five volts and two 29 millisecond pulse: dnrati~n.
WO 99/61100 PCT/US99/11376 ..
2 Conduction Speed Transverse to Fiber Direction, 2 cosec 3 duration S Cathodal Monophasic 13.9 ~ 2.5 21.4 t 2.6 cm/sec23.3 ~ 3.0 cm/sec cm/sec 6 Anodal Monophasic 24.0 t 2.3 27.5 t 2.1 cm/sec31.3 t 1.7 cm/sec cm/sec 7 Leading Cathodal Biphasic27.1 = 1.2 28.2 ~ 2.3 cm/sec27.5 ~ 1.8 cm/sec em/sec 8 Leading Anodal Biphasic26.8 ~ 2.1 28.5 ~ 0.7 cm/sec29.7 ~ 1.8 cm/sec cm/sec 9 Table 2 disc'.oses the conduction speed along fiber direction for each stimulation protocol administered, with stimulations of three, four and five volts and two millisecond 11 pulse duration.
Conduction Speed Along Fiber Direction, 2 cosec stimulation 1S Cathodal',',~onu; 45.3 ~ 0.9 em/sec47.4 ~ 1.8 49.7 ~ 1.S
i:a<i~: cm/sec cm/sec 16 Anodal Monophasic 48.1 ~ 1.2 crn/secS 1.8 ~ O.S 54.9 t 0.7 cm/sec cm/sec 17 Leading Cathodal Su.8 t O.y cm/sec52.6 t 1.1 52.8 t 1.7 Biphasic em/see cm/sec 18 Leading ?~nc~~aal 52.6 t 2.5 cm/secSS.3 t 1.S 54.2 t 2.3 Biphasic em/sec cm/sec 19 The differences in conduction velocities between the cathodal monophasic, anodal monophasic, leading cathodal bipl~asic and leading anodal biphasic were found to be 21 significant (p < 0.001 ). From the transmembrane potential measurements, the maximum 22 upstroke ((d~l,'c';::~ax} of the a. ~ior. potentials was found to correlate well with the changes in 23 conduction velocity in fne longitudinal direction. For a four volt pulse of two millisecond 24 duration, (dV/dt}coax was 63.5 t 2.4 V/sec for cathodal and 7S.S t S.6 V/sec for anodal 2S pulses.
27 The effects of v~ Tying pacing protocols on cardiac electrophysiology were analyzed 28 using Langendorff prepared isolated rabbit hearts. Stimulation was applied to the heart at a 29 constant voltage rectangular pulse. The following protocols were examined:
monophasic 1 anodal pulse, monophasic cathodal pulse, leading anodal biphasic pulse, and leading cathodal 2 biphasic pulse. Administered voltage was increased in one volt steps from one to five volts 3 for both anodal and cathodal stimulation. Duration was increased in two millisecond steps 4 from two to ten n:.illiseconds. Epicardial conduction velocities were measured along and transverse to tire left ventricular fiber direction at a distance between three to six millimeters 6 from the left ventricular free wall. Figs. 6 and 7 depict the effects of stimulation pulse 7 duration and the protocol of stimulation administered on the conduction velocities.
g Fig. 6 depicts the velocities measured between three millimeters and six millimeters 9 transverse to the fiber direction. In this region, cathodal monophasic stimulation 602 demonstrates the slowest conduction velocity for each stimulation pulse duration tested. This 11 is followed by modal tronophz.sic stimulation 604 and leading cathodal biphasic stimulation 12 606. The fastest conduction velocity is demonstrated by leading anodal biphasic stimulation 13 608.
14 Fig. 7 depicts the velocities measured between three millimeters and six millimeters parallel to the fiber directior_. In this region, cathodal monophasic stimulation 702 16 demonstrates the slowest conduction velocity for each stimulation pulse duration tested.
17 Velocity results of ar_odai monophasic stimulation 704 and leading cathodal biphasic 18 stimulation 706 are similar to those with anodal monophasic stimulation, but demonstrating 19 slightly quicker speeds. The fastest conduction velocity is demonstrated by leading anodal biphasic stimulation 708.
21 In one aspect of the invention, electrical stimulation is administered to the cardiac 22 muscle. The ano3ai stimulation component of biphasic electrical stimulation augments 23 cardiac contractilit;~ by hvperpolarizing the tissue prior to excitation, leading to faster impulse 24 conduction, mire intrsceliuiar calcium release, and the resulting superior cardiac contraction.
The cathodal stmulaticn component eliminates the drawbacks of anodal stimulation, 26 resulting in e:fective cardiac stimulation at a lower voltage level than would be required with 27 anodal stimulation alone. This, in turn, extends pacemaker battery life and reduces tissue 28 damage.
29 In a second aspect of the invention, biphasic electrical stimulation is administered to the cardiac bloods yool, that is, sae blood entering and surrounding the heart. This enables 31 cardiac stimulation without the necessity of placing electrical leads in intimate contact with 1 cardiac tissue, thereby diminishing the likelihood of damage to this tissue.
The stimulation 2 threshold of biphasic sti.nulation administered via the blood pool is in the same range as 3 standard stimuli delivered directly to the heart muscle. Through the use of biphasic electrical 4 stimulation to the cardiac blood pool it is therefore possible to achieve enhanced cardiac contraction, without ske:etal muscle contraction, cardiac muscle damage or adverse effects to 6 the blood pool.
7 In a third aspect of the invention, biphasic electrical stimulation is applied to striated 8 (skeletal) muscle tissue. The combination of anodal with cathodal stimulation results in the 9 contraction of a greater number of muscle motor units at lower levels of voltage and/or electrical current, resulting in improved muscle response. The benefits of the present 1 I invention are realized both when there is direct stimulation, as well as when the stimulation is 12 indirect (througri the skin). Benefits may be realized in physical therapy and muscle 13 rehabilitation contexts, for example, stimulation of muscles over time while waiting for 14 damaged nerves to regenerate.
In a fourth aspect of the invention, biphasic electrical stimulation is applied to smooth 16 muscle tissue. Visceral smooth muscle is found in the walls of hollow visceral organs such 17 as the stomacri, intestines, urinary bladder and uterus. The fibers of smooth muscles are 18 capable of stimulating each other. Thus, once one fiber is stimulated, the depolarization wave 19 moving over its surface may excite adjacent fibers, which in turn stimulate still others.
Benefits of such sT~mulatior, ca.~: be realized, for example, in situations where incontinence 21 has been caused by trauma or disease.
22 HavirLg thllS described the basic concept of the invention, it will be readily apparent to 23 those skilled in the art that the foregoing detailed disclosure is intended to be presented by 24 way of example aniy. and is not limiting. Various alterations, improvements and modifications vrili occur and are intended to those skilled in the art, but are not expressly 26 stated herein. ~ ilese modifications, alterations and improvements are intended to be 27 suggested hereby, and within the scope of the invention. Further, the stimulating pulses 28 described in this specification are well within the capabilities of existing electronics with 29 appropriate programming. Biphasic stimulation as provided by the present invention may be desirable in additional situations where ele ctrical stimulation is indicated;
such as, nerve 31 tissue stimulation gird bone Z.issu~ stimulation. Accordingly, the invention is limited only by WO 99/61100 PCTlUS99/11376 the following claims and equivalents thereto.
Fig.
11 1 depicts biphasic electrical stimulation wherein a first stimulation phase, comprising anodal 12 stimulus 102, is administered having amplitude 104 and duration 106. This first stimulation 13 phase is immediately followed by a second stimulation phase comprising cathodal stimulation 14 108 of equal intensity and duration.
Fig. 2 depicts biphasic electrical stimulation wherein a first stimulation phase, 16 comprising cathodal stimulation 202 having amplitude 204 and duration 206, is administered.
17 This first stimulation phase is immediately followed by a second stimulation phase 18 comprising anodal stimulation 208 of equal intensity and duration.
19 Fig. 3 depicTs a preferred embodiment of the present invention wherein a first stimulation phase, comprising low level, long duration anodal stimulation 302 having 21 amplitude 304 ansl duration 306, is administered. This first stimulation phase is immediately 22 followed by a second stimulation phase comprising cathodal stimulation 308 of conventional 23 intensity and duration. In an alternative embodiment of the invention, anodal stimulation 302 24 is at maximum subthresizold amplitude. In yet another alternative embodiment of the invention, anodal stimulation 302 is less than three volts. In another alternative embodiment 26 of the invention, anodal stimulation 302 is a duration of approximately two to eight 27 milliseconds. In vet another alternative embodiment of the invention, cathodal stimulation 28 308 is of a short duration. In another alternative embodiment of the invention, cathodal 29 stimulation 308 is approximately 0.3 to 0.8 millisecond. In yet another alternative 1 embodiment of the invention, cathodal stimulation 308 is of a high amplitude. In another 2 alternative embodiment of the invention, cathodal stimulation 308 is in the approximate range 3 of three to twenty volts. In yet another alternative embodiment of the present invention, 4 cathodal stimulation 308 is of a duration less than 0.3 millisecond and at a voltage greater than twenty volts. In another alternati~~e embodiment of the present invention, cathodal 6 stimulation 308 lasts as long as 6.0 milliseconds and has a voltage as low as 200 rnillivolts.
7 In the manner disclosed by these embodiments, as well as those alterations and modifications 8 which may become obvioL~s upon the reading of this specification, a maximum membrane 9 potential without activation is achieved in the first phase of stimulation.
Fig. 4 depicts an alternative preferred embodiment of the present invention wherein a 11 first stimulation~pl~ase. comprising anodal stimulation 402, is administered over period 404 12 with rising intensity level 406. The ramp of rising intensity level 406 may be linear or non-13 linear, and the slope may vary. This anodal stimulation is immediately followed by a second 14 stimulation phase comprising cathodal stimulation 408 of conventional intensity and duration. In an alternati~~e embodiment of the invention, anodal stimulation 402 rises to a 16 maximum subthreshold amplitude. In yet another alternative embodiment of the invention, 17 anodal stimulation 402 rises to a maximum amplitude that is less than three volts. In another 18 alternative embodiment of the invention, anodal stimulation 402 is a duration of 19 approximately two to eight milliseconds. In yet another alternative embodiment of the invention. cathodal stimulation 408 l s of a short duration. In another alternative embodiment 21 of the invention. catl~odal stimulation 408 is approximately 0.3 to 0.8 millisecond. In yet 22 another alternative embodiment of the invention, cathodal stimulation 408 is of a high 23 amplitude. In another aiiernative embodiment of the invention, cathodal stimulation 408 is in 24 the approximate range of thYee to twenty volts. In yet another alternative embodiment of the present invention, cathodal :,timulation 408 is of a duration less than 0.3 milliseconds and at a 26 voltage greater than t<venty volts. In another alternative embodiment of the present invention, 27 cathodal stimulation 108 lasts as long as 6.0 milliseconds and has a voltage as low as 200 28 millivolts. In the rrarner disclosed by these embodiments, as well as those alterations and 29 modifications which may become obvious upon the reading of this specification, a maximum membrane potential without activation is achieved in the first phase of stimulation.
31 Fig. 5 depicts binhasic electrical stimulation wherein a first stimulation phase, WO 99/61100 PCr/US99/11376 _, 1 comprising series 502 of anodal pulses, is administered at amplitude 504. In one 2 embodiment, rest period 506 is of equal duration to stimulation period 508, and is 3 administered at baseline amplitude. In an alternative embodiment, rest period 506 is of a 4 differing duration than stimulation period 508 and is administered at baseline amplitude.
Rest period 506 occurs after each stim°alation period 508, with the exception that a second 6 stimulation phase, comprising cathodal stimulation 510 of conventional intensity and 7 duration, immediatel:~ follows the completion of series 502. In an alternative embodiment of 8 the invention. the total :barge transferred through series S02 of anodal stimulation is at the 9 maximum subthreshold level. In another alternative embodiment of the invention, cathodal stimulation 510 is of a Short d~wation. In yet another alternative embodiment of the invention, 11 cathodal stimulation 510 is appro~:imately 0.3 to 0.8 millisecond. In another alternative 12 embodiment of the invention, cathodal stimulation 510 is of a high amplitude. In yet another 13 alternative embodiment of the invention, cathodal stimulation 510 is in the approximate range 14 of three to twenty volts. In another alternative embodiment of the invention, cathodal stimulation 510 is of a duration less than 0.3 millisecond and at a voltage greater than twenty 16 volts. In another alternative embodiment of the present invention, cathodal stimulation 510 17 lasts as long as 6.0 milliseconds and has a voltage as low as 200 millivolts.
19 Stimulation and proYagation characteristics of the myocardium were studied in isolated hearts using pulses of differing polarities and phases. 'The experiments were earned 21 out in five isolated Langendo-tf perfused rabbit hearts. Conduction velocity on the 22 epicardium was treasured using an array of bipolar electrodes. Measurements were made 23 between six millimeters ane ni:-~e millimeters from the stimulation site.
Transmembrane 24 potential was recorded using a floating intracellular microelectrode. The following protocols were examined: mono ~zsi : cathodal pulse., monophasic anodal pulse, leading cathodal 26 biphasic pulse, anal leading anodal bzphasic pulse.
2~ Table 1 discloses the conduction speed transverse to fiber direction for each 28 stimulation protocol acuninistersd. with stimulations of three, four and five volts and two 29 millisecond pulse: dnrati~n.
WO 99/61100 PCT/US99/11376 ..
2 Conduction Speed Transverse to Fiber Direction, 2 cosec 3 duration S Cathodal Monophasic 13.9 ~ 2.5 21.4 t 2.6 cm/sec23.3 ~ 3.0 cm/sec cm/sec 6 Anodal Monophasic 24.0 t 2.3 27.5 t 2.1 cm/sec31.3 t 1.7 cm/sec cm/sec 7 Leading Cathodal Biphasic27.1 = 1.2 28.2 ~ 2.3 cm/sec27.5 ~ 1.8 cm/sec em/sec 8 Leading Anodal Biphasic26.8 ~ 2.1 28.5 ~ 0.7 cm/sec29.7 ~ 1.8 cm/sec cm/sec 9 Table 2 disc'.oses the conduction speed along fiber direction for each stimulation protocol administered, with stimulations of three, four and five volts and two millisecond 11 pulse duration.
Conduction Speed Along Fiber Direction, 2 cosec stimulation 1S Cathodal',',~onu; 45.3 ~ 0.9 em/sec47.4 ~ 1.8 49.7 ~ 1.S
i:a<i~: cm/sec cm/sec 16 Anodal Monophasic 48.1 ~ 1.2 crn/secS 1.8 ~ O.S 54.9 t 0.7 cm/sec cm/sec 17 Leading Cathodal Su.8 t O.y cm/sec52.6 t 1.1 52.8 t 1.7 Biphasic em/see cm/sec 18 Leading ?~nc~~aal 52.6 t 2.5 cm/secSS.3 t 1.S 54.2 t 2.3 Biphasic em/sec cm/sec 19 The differences in conduction velocities between the cathodal monophasic, anodal monophasic, leading cathodal bipl~asic and leading anodal biphasic were found to be 21 significant (p < 0.001 ). From the transmembrane potential measurements, the maximum 22 upstroke ((d~l,'c';::~ax} of the a. ~ior. potentials was found to correlate well with the changes in 23 conduction velocity in fne longitudinal direction. For a four volt pulse of two millisecond 24 duration, (dV/dt}coax was 63.5 t 2.4 V/sec for cathodal and 7S.S t S.6 V/sec for anodal 2S pulses.
27 The effects of v~ Tying pacing protocols on cardiac electrophysiology were analyzed 28 using Langendorff prepared isolated rabbit hearts. Stimulation was applied to the heart at a 29 constant voltage rectangular pulse. The following protocols were examined:
monophasic 1 anodal pulse, monophasic cathodal pulse, leading anodal biphasic pulse, and leading cathodal 2 biphasic pulse. Administered voltage was increased in one volt steps from one to five volts 3 for both anodal and cathodal stimulation. Duration was increased in two millisecond steps 4 from two to ten n:.illiseconds. Epicardial conduction velocities were measured along and transverse to tire left ventricular fiber direction at a distance between three to six millimeters 6 from the left ventricular free wall. Figs. 6 and 7 depict the effects of stimulation pulse 7 duration and the protocol of stimulation administered on the conduction velocities.
g Fig. 6 depicts the velocities measured between three millimeters and six millimeters 9 transverse to the fiber direction. In this region, cathodal monophasic stimulation 602 demonstrates the slowest conduction velocity for each stimulation pulse duration tested. This 11 is followed by modal tronophz.sic stimulation 604 and leading cathodal biphasic stimulation 12 606. The fastest conduction velocity is demonstrated by leading anodal biphasic stimulation 13 608.
14 Fig. 7 depicts the velocities measured between three millimeters and six millimeters parallel to the fiber directior_. In this region, cathodal monophasic stimulation 702 16 demonstrates the slowest conduction velocity for each stimulation pulse duration tested.
17 Velocity results of ar_odai monophasic stimulation 704 and leading cathodal biphasic 18 stimulation 706 are similar to those with anodal monophasic stimulation, but demonstrating 19 slightly quicker speeds. The fastest conduction velocity is demonstrated by leading anodal biphasic stimulation 708.
21 In one aspect of the invention, electrical stimulation is administered to the cardiac 22 muscle. The ano3ai stimulation component of biphasic electrical stimulation augments 23 cardiac contractilit;~ by hvperpolarizing the tissue prior to excitation, leading to faster impulse 24 conduction, mire intrsceliuiar calcium release, and the resulting superior cardiac contraction.
The cathodal stmulaticn component eliminates the drawbacks of anodal stimulation, 26 resulting in e:fective cardiac stimulation at a lower voltage level than would be required with 27 anodal stimulation alone. This, in turn, extends pacemaker battery life and reduces tissue 28 damage.
29 In a second aspect of the invention, biphasic electrical stimulation is administered to the cardiac bloods yool, that is, sae blood entering and surrounding the heart. This enables 31 cardiac stimulation without the necessity of placing electrical leads in intimate contact with 1 cardiac tissue, thereby diminishing the likelihood of damage to this tissue.
The stimulation 2 threshold of biphasic sti.nulation administered via the blood pool is in the same range as 3 standard stimuli delivered directly to the heart muscle. Through the use of biphasic electrical 4 stimulation to the cardiac blood pool it is therefore possible to achieve enhanced cardiac contraction, without ske:etal muscle contraction, cardiac muscle damage or adverse effects to 6 the blood pool.
7 In a third aspect of the invention, biphasic electrical stimulation is applied to striated 8 (skeletal) muscle tissue. The combination of anodal with cathodal stimulation results in the 9 contraction of a greater number of muscle motor units at lower levels of voltage and/or electrical current, resulting in improved muscle response. The benefits of the present 1 I invention are realized both when there is direct stimulation, as well as when the stimulation is 12 indirect (througri the skin). Benefits may be realized in physical therapy and muscle 13 rehabilitation contexts, for example, stimulation of muscles over time while waiting for 14 damaged nerves to regenerate.
In a fourth aspect of the invention, biphasic electrical stimulation is applied to smooth 16 muscle tissue. Visceral smooth muscle is found in the walls of hollow visceral organs such 17 as the stomacri, intestines, urinary bladder and uterus. The fibers of smooth muscles are 18 capable of stimulating each other. Thus, once one fiber is stimulated, the depolarization wave 19 moving over its surface may excite adjacent fibers, which in turn stimulate still others.
Benefits of such sT~mulatior, ca.~: be realized, for example, in situations where incontinence 21 has been caused by trauma or disease.
22 HavirLg thllS described the basic concept of the invention, it will be readily apparent to 23 those skilled in the art that the foregoing detailed disclosure is intended to be presented by 24 way of example aniy. and is not limiting. Various alterations, improvements and modifications vrili occur and are intended to those skilled in the art, but are not expressly 26 stated herein. ~ ilese modifications, alterations and improvements are intended to be 27 suggested hereby, and within the scope of the invention. Further, the stimulating pulses 28 described in this specification are well within the capabilities of existing electronics with 29 appropriate programming. Biphasic stimulation as provided by the present invention may be desirable in additional situations where ele ctrical stimulation is indicated;
such as, nerve 31 tissue stimulation gird bone Z.issu~ stimulation. Accordingly, the invention is limited only by WO 99/61100 PCTlUS99/11376 the following claims and equivalents thereto.
Claims (10)
1. An apparatus for stimulating muscle tissue with biphasic waveforms, comprising:
pulse generation electronics that generates a pulse, the pulse defining a first stimulation phase and defining a second stimulation phase, wherein the first stimulation phase has a first phase polarity, a first phase amplitude, a first phase shape, and a first phase duration for preconditioning the muscle tissue to accept subsequent stimulation, and wherein the second stimulation phase has a polarity opposite to the first phase polarity, a second phase amplitude that is larger in absolute value than the first phase amplitude, a second phase shape, and a second phase duration; and leads connected to the pulse generation electronics and being adapted to apply the first stimulation phase and the second stimulation phase in sequence to the muscle tissue, wherein the muscle tissue is selected from the group consisting of striated muscle, smooth muscle and mixed muscle;
wherein the first phase amplitude is ramped from a baseline value to a second value.
pulse generation electronics that generates a pulse, the pulse defining a first stimulation phase and defining a second stimulation phase, wherein the first stimulation phase has a first phase polarity, a first phase amplitude, a first phase shape, and a first phase duration for preconditioning the muscle tissue to accept subsequent stimulation, and wherein the second stimulation phase has a polarity opposite to the first phase polarity, a second phase amplitude that is larger in absolute value than the first phase amplitude, a second phase shape, and a second phase duration; and leads connected to the pulse generation electronics and being adapted to apply the first stimulation phase and the second stimulation phase in sequence to the muscle tissue, wherein the muscle tissue is selected from the group consisting of striated muscle, smooth muscle and mixed muscle;
wherein the first phase amplitude is ramped from a baseline value to a second value.
2. An apparatus for stimulating muscle tissue with biphasic waveforms, comprising:
pulse generation electronics that generates a pulse, the pulse defining a first stimulation phase and defining a second stimulation phase, wherein the first stimulation phase has a first phase polarity, a first phase amplitude, a first phase shape, and a first phase duration for preconditioning the muscle tissue to accept subsequent stimulation, and wherein the second stimulation phase has a polarity opposite to the first phase polarity, a second phase amplitude that is larger in absolute value than the first phase amplitude, a second phase shape, and a second phase duration; and leads connected to the pulse generation electronics and being adapted to apply the first stimulation phase and the second stimulation phase in sequence to the muscle tissue, wherein the muscle tissue is selected from the group consisting of striated muscle, smooth muscle and mixed muscle;
wherein the first phase amplitude is ramped from a baseline value to a second value, and wherein the absolute value of the second value is equal to the absolute value of the second phase amplitude.
pulse generation electronics that generates a pulse, the pulse defining a first stimulation phase and defining a second stimulation phase, wherein the first stimulation phase has a first phase polarity, a first phase amplitude, a first phase shape, and a first phase duration for preconditioning the muscle tissue to accept subsequent stimulation, and wherein the second stimulation phase has a polarity opposite to the first phase polarity, a second phase amplitude that is larger in absolute value than the first phase amplitude, a second phase shape, and a second phase duration; and leads connected to the pulse generation electronics and being adapted to apply the first stimulation phase and the second stimulation phase in sequence to the muscle tissue, wherein the muscle tissue is selected from the group consisting of striated muscle, smooth muscle and mixed muscle;
wherein the first phase amplitude is ramped from a baseline value to a second value, and wherein the absolute value of the second value is equal to the absolute value of the second phase amplitude.
3. An apparatus for stimulating muscle tissue with biphasic waveforms, comprising:
pulse generation electronics that generates a pulse, the pulse defining a first stimulation phase and defining a second stimulation phase, wherein the first stimulation phase has a first phase polarity, a first phase amplitude, a first phase shape, and a first phase duration for preconditioning the muscle tissue to accept subsequent stimulation, and wherein the second stimulation phase has a polarity opposite to the first phase polarity, a second phase amplitude that is larger in absolute value than the first phase amplitude, a second phase shape, and a second phase duration; and leads connected to the pulse generation electronics and being adapted to apply the first stimulation phase and the second stimulation phase in sequence to the muscle tissue, wherein the muscle tissue is selected from the group consisting of striated muscle, smooth muscle and mixed muscle;
wherein the first stimulation phase further comprises a series of stimulating pulses of a predetermined amplitude, polarity, and duration.
pulse generation electronics that generates a pulse, the pulse defining a first stimulation phase and defining a second stimulation phase, wherein the first stimulation phase has a first phase polarity, a first phase amplitude, a first phase shape, and a first phase duration for preconditioning the muscle tissue to accept subsequent stimulation, and wherein the second stimulation phase has a polarity opposite to the first phase polarity, a second phase amplitude that is larger in absolute value than the first phase amplitude, a second phase shape, and a second phase duration; and leads connected to the pulse generation electronics and being adapted to apply the first stimulation phase and the second stimulation phase in sequence to the muscle tissue, wherein the muscle tissue is selected from the group consisting of striated muscle, smooth muscle and mixed muscle;
wherein the first stimulation phase further comprises a series of stimulating pulses of a predetermined amplitude, polarity, and duration.
4. An apparatus for stimulating muscle tissue with biphasic waveforms, comprising:
pulse generation electronics that generates a pulse, the pulse defining a first stimulation phase and defining a second stimulation phase, wherein the first stimulation phase has a first phase polarity, a first phase amplitude, a first phase shape, and a first phase duration for preconditioning the muscle tissue to accept subsequent stimulation, and wherein the second stimulation phase has a polarity opposite to the first phase polarity, a second phase amplitude that is larger in absolute value than the first phase amplitude, a second phase shape, and a second phase duration; and leads connected to the pulse generation electronics and being adapted to apply the first stimulation phase and the second stimulation phase in sequence to the muscle tissue, wherein the muscle tissue is selected from the group consisting of striated muscle, smooth muscle and mixed muscle;
wherein the first phase polarity is positive and has a maximum subthreshold amplitude of about 0.5 to 3.5 volts.
pulse generation electronics that generates a pulse, the pulse defining a first stimulation phase and defining a second stimulation phase, wherein the first stimulation phase has a first phase polarity, a first phase amplitude, a first phase shape, and a first phase duration for preconditioning the muscle tissue to accept subsequent stimulation, and wherein the second stimulation phase has a polarity opposite to the first phase polarity, a second phase amplitude that is larger in absolute value than the first phase amplitude, a second phase shape, and a second phase duration; and leads connected to the pulse generation electronics and being adapted to apply the first stimulation phase and the second stimulation phase in sequence to the muscle tissue, wherein the muscle tissue is selected from the group consisting of striated muscle, smooth muscle and mixed muscle;
wherein the first phase polarity is positive and has a maximum subthreshold amplitude of about 0.5 to 3.5 volts.
5. An apparatus for stimulating muscle tissue with biphasic waveforms, comprising:
pulse generation electronics that generates a pulse, the pulse defining a first stimulation phase and defining a second stimulation phase, wherein the first stimulation phase has a first phase polarity, a first phase amplitude, a first phase shape, and a first phase duration for preconditioning the muscle tissue to accept subsequent stimulation, and wherein the second stimulation phase has a polarity opposite to the first phase polarity, a second phase amplitude that is larger in absolute value than the first phase amplitude, a second phase shape, and a second phase duration; and leads connected to the pulse generation electronics and being adapted to apply the first stimulation phase and the second stimulation phase in sequence to the muscle tissue, wherein the muscle tissue is selected from the group consisting of striated muscle, smooth muscle and mixed muscle;
wherein the first phase duration is at least as long as the second phase duration and the first phase duration is about one to nine milliseconds.
pulse generation electronics that generates a pulse, the pulse defining a first stimulation phase and defining a second stimulation phase, wherein the first stimulation phase has a first phase polarity, a first phase amplitude, a first phase shape, and a first phase duration for preconditioning the muscle tissue to accept subsequent stimulation, and wherein the second stimulation phase has a polarity opposite to the first phase polarity, a second phase amplitude that is larger in absolute value than the first phase amplitude, a second phase shape, and a second phase duration; and leads connected to the pulse generation electronics and being adapted to apply the first stimulation phase and the second stimulation phase in sequence to the muscle tissue, wherein the muscle tissue is selected from the group consisting of striated muscle, smooth muscle and mixed muscle;
wherein the first phase duration is at least as long as the second phase duration and the first phase duration is about one to nine milliseconds.
6. ~An apparatus for stimulating muscle tissue with biphasic waveforms, comprising:
pulse generation electronics that generates a pulse, the pulse defining a first stimulation phase and defining a second stimulation phase, wherein the first stimulation phase has a first phase polarity, a first phase amplitude, a first phase shape, and a first phase duration for preconditioning the muscle tissue to accept subsequent stimulation, and wherein the second stimulation phase has a polarity opposite to the first phase polarity, a second phase amplitude that is larger in absolute value than the first phase amplitude, a second phase shape, and a second phase duration; and leads connected to the pulse generation electronics and being adapted to apply the first stimulation phase and the second stimulation phase in sequence to the muscle tissue, wherein the muscle tissue is selected from the group consisting of striated muscle, smooth muscle and mixed muscle;
wherein the first phase duration is at least as long as the second phase duration and the second phase duration is about 0.2 to 0.9 millisecond.
pulse generation electronics that generates a pulse, the pulse defining a first stimulation phase and defining a second stimulation phase, wherein the first stimulation phase has a first phase polarity, a first phase amplitude, a first phase shape, and a first phase duration for preconditioning the muscle tissue to accept subsequent stimulation, and wherein the second stimulation phase has a polarity opposite to the first phase polarity, a second phase amplitude that is larger in absolute value than the first phase amplitude, a second phase shape, and a second phase duration; and leads connected to the pulse generation electronics and being adapted to apply the first stimulation phase and the second stimulation phase in sequence to the muscle tissue, wherein the muscle tissue is selected from the group consisting of striated muscle, smooth muscle and mixed muscle;
wherein the first phase duration is at least as long as the second phase duration and the second phase duration is about 0.2 to 0.9 millisecond.
7. ~An apparatus for stimulating muscle tissue with biphasic waveforms, comprising:
pulse generation electronics that generates a pulse, the pulse defining a first stimulation phase and defining a second stimulation phase, wherein the first stimulation phase has a first phase polarity, a first phase amplitude, a first phase shape, and a first phase duration for preconditioning the muscle tissue to accept subsequent stimulation, and wherein the second stimulation phase has a polarity opposite to the first phase polarity, a second phase amplitude that is larger in absolute value than the first phase amplitude, a second phase shape, and a second phase duration; and leads connected to the pulse generation electronics and being adapted to apply the first stimulation phase and the second stimulation phase in sequence to the muscle tissue, wherein the muscle tissue is selected from the group consisting of striated muscle, smooth muscle and mixed muscle;
wherein the second phase amplitude is about two volts to twenty volts.
pulse generation electronics that generates a pulse, the pulse defining a first stimulation phase and defining a second stimulation phase, wherein the first stimulation phase has a first phase polarity, a first phase amplitude, a first phase shape, and a first phase duration for preconditioning the muscle tissue to accept subsequent stimulation, and wherein the second stimulation phase has a polarity opposite to the first phase polarity, a second phase amplitude that is larger in absolute value than the first phase amplitude, a second phase shape, and a second phase duration; and leads connected to the pulse generation electronics and being adapted to apply the first stimulation phase and the second stimulation phase in sequence to the muscle tissue, wherein the muscle tissue is selected from the group consisting of striated muscle, smooth muscle and mixed muscle;
wherein the second phase amplitude is about two volts to twenty volts.
8. ~An apparatus for stimulating muscle tissue with biphasic waveforms, comprising:
pulse generation electronics that generates a pulse, the pulse defining a first stimulation phase and defining a second stimulation phase, wherein the first stimulation phase has a first phase polarity, a first phase amplitude, a first phase shape, and a first phase duration for preconditioning the muscle tissue to accept subsequent stimulation, and wherein the second stimulation phase has a polarity opposite to the first phase polarity, a second phase amplitude that is larger in absolute value than the first phase amplitude, a second phase shape, and a second phase duration; and leads connected to the pulse generation electronics and being adapted to apply the first stimulation phase and the second stimulation phase in sequence to the muscle tissue, wherein the muscle tissue is selected from the group consisting of striated muscle, smooth muscle and mixed muscle;
wherein the second phase duration is less than 0.3 milliseconds and the second phase amplitude is greater than twenty volts.
pulse generation electronics that generates a pulse, the pulse defining a first stimulation phase and defining a second stimulation phase, wherein the first stimulation phase has a first phase polarity, a first phase amplitude, a first phase shape, and a first phase duration for preconditioning the muscle tissue to accept subsequent stimulation, and wherein the second stimulation phase has a polarity opposite to the first phase polarity, a second phase amplitude that is larger in absolute value than the first phase amplitude, a second phase shape, and a second phase duration; and leads connected to the pulse generation electronics and being adapted to apply the first stimulation phase and the second stimulation phase in sequence to the muscle tissue, wherein the muscle tissue is selected from the group consisting of striated muscle, smooth muscle and mixed muscle;
wherein the second phase duration is less than 0.3 milliseconds and the second phase amplitude is greater than twenty volts.
9. ~An apparatus for stimulating muscle tissue with biphasic waveforms, comprising:
pulse generation electronics that generates a pulse, the pulse defining a first stimulation phase and defining a second stimulation phase, wherein the first stimulation phase has a first phase polarity, a first phase amplitude, a first phase shape, and a first phase duration for preconditioning the muscle tissue to accept subsequent stimulation, and wherein the second stimulation phase has a polarity opposite to the first phase polarity, a second phase amplitude that is larger in absolute value than the first phase amplitude, a second phase shape, and a second phase duration; and leads connected to the pulse generation electronics and being adapted to apply the first stimulation phase and the second stimulation phase in sequence to the muscle tissue, wherein the muscle tissue is selected from the group consisting of striated muscle, smooth muscle and mixed muscle;
wherein the stimulation to the muscle is selected from the group consisting of direct stimulation to the muscle and indirect stimulation to the muscle; and wherein the indirect stimulation is administered through skin.
pulse generation electronics that generates a pulse, the pulse defining a first stimulation phase and defining a second stimulation phase, wherein the first stimulation phase has a first phase polarity, a first phase amplitude, a first phase shape, and a first phase duration for preconditioning the muscle tissue to accept subsequent stimulation, and wherein the second stimulation phase has a polarity opposite to the first phase polarity, a second phase amplitude that is larger in absolute value than the first phase amplitude, a second phase shape, and a second phase duration; and leads connected to the pulse generation electronics and being adapted to apply the first stimulation phase and the second stimulation phase in sequence to the muscle tissue, wherein the muscle tissue is selected from the group consisting of striated muscle, smooth muscle and mixed muscle;
wherein the stimulation to the muscle is selected from the group consisting of direct stimulation to the muscle and indirect stimulation to the muscle; and wherein the indirect stimulation is administered through skin.
10. ~An apparatus for stimulating muscle tissue with biphasic waveforms, comprising:
pulse generation electronics that generates a pulse, the pulse defining a first stimulation phase and defining a second stimulation phase;
wherein the first stimulation phase has a positive polarity, a first phase amplitude, a first phase shape, and a first phase duration, where the first phase amplitude is about 0.5 to 3.5 volts, and the first phase duration is about one to nine milliseconds; and wherein the second stimulation phase has a negative polarity, a second phase amplitude that is larger in absolute value than the first phase amplitude, a second phase shape, and a second phase duration, where the second phase amplitude is about two volts to twenty volts, and the second phase duration is about 0.2 to 0.9 millisecond; and leads connected to the pulse generation electronics and being adapted to apply the first stimulation phase and the second stimulation phase in sequence to the muscle tissue, wherein the muscle tissue is selected from the group consisting of striated muscle, smooth muscle and mixed muscle, and wherein the stimulation to the muscle is selected from the group consisting of direct stimulation to the muscle and indirect stimulation to the muscle.
pulse generation electronics that generates a pulse, the pulse defining a first stimulation phase and defining a second stimulation phase;
wherein the first stimulation phase has a positive polarity, a first phase amplitude, a first phase shape, and a first phase duration, where the first phase amplitude is about 0.5 to 3.5 volts, and the first phase duration is about one to nine milliseconds; and wherein the second stimulation phase has a negative polarity, a second phase amplitude that is larger in absolute value than the first phase amplitude, a second phase shape, and a second phase duration, where the second phase amplitude is about two volts to twenty volts, and the second phase duration is about 0.2 to 0.9 millisecond; and leads connected to the pulse generation electronics and being adapted to apply the first stimulation phase and the second stimulation phase in sequence to the muscle tissue, wherein the muscle tissue is selected from the group consisting of striated muscle, smooth muscle and mixed muscle, and wherein the stimulation to the muscle is selected from the group consisting of direct stimulation to the muscle and indirect stimulation to the muscle.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US09/085,360 US6141587A (en) | 1996-08-19 | 1998-05-27 | Augmentation of muscle contractility by biphasic stimulation |
| US09/085,360 | 1998-05-27 | ||
| PCT/US1999/011376 WO1999061100A1 (en) | 1998-05-27 | 1999-05-21 | Augmentation of muscle contractility by biphasic stimulation |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2333360A1 CA2333360A1 (en) | 1999-12-02 |
| CA2333360C true CA2333360C (en) | 2003-11-25 |
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| CA002333360A Expired - Fee Related CA2333360C (en) | 1998-05-27 | 1999-05-21 | Augmentation of muscle contractility by biphasic stimulation |
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| US (1) | US6141587A (en) |
| EP (1) | EP1079892B1 (en) |
| JP (3) | JP2002516161A (en) |
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| AT (1) | ATE300973T1 (en) |
| AU (1) | AU749212B2 (en) |
| BR (1) | BR9910731A (en) |
| CA (1) | CA2333360C (en) |
| DE (1) | DE69926501T2 (en) |
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| ES (1) | ES2246087T3 (en) |
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| TR (1) | TR200003494T2 (en) |
| UA (1) | UA66384C2 (en) |
| WO (1) | WO1999061100A1 (en) |
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- 1999-05-21 ID IDW20002431A patent/ID27941A/en unknown
- 1999-05-21 NZ NZ530452A patent/NZ530452A/en unknown
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- 1999-05-21 JP JP2000550555A patent/JP2002516161A/en active Pending
- 1999-05-21 CA CA002333360A patent/CA2333360C/en not_active Expired - Fee Related
- 1999-05-21 AU AU40952/99A patent/AU749212B2/en not_active Ceased
- 1999-05-21 BR BR9910731-7A patent/BR9910731A/en not_active Application Discontinuation
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107635496A (en) * | 2015-05-12 | 2018-01-26 | 圣犹达医疗用品电生理部门有限公司 | For exchanging the asymmetrical balance waveform of the irreversible electroporation of heart |
| CN107635496B (en) * | 2015-05-12 | 2021-08-17 | 圣犹达医疗用品电生理部门有限公司 | Asymmetric balanced waveforms for alternating current cardiac irreversible electroporation |
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