SYSTEM AND METHOD TO MANAGE CARDIACA DA INA REMODELING
Description of the Invention This application is generally related to the treatment of the heart, and more particularly to manage and prevent the damaging cardiac remodeling that follows a myocardial infarction. Heart remodeling is a dangerous physical change in the heart that occurs with heart failure, heart attack, and heart disease. The remodeling is characterized by enlargement of the heart and thinning of the walls of the heart. For example, after a heart attack, while the normal heart muscle responds normally to excitatory impulses, the tissue that is damaged by the heart attack does not respond or respond in a slower way than the normal speed to excitatory impulses. Healthy tissue, however, which continues to function normally, places increased tension on damaged and marginalized tissue, thereby "spreading" it. The extension increases the volume of blood maintained by the heart which results in an increased blood output in the short term by means of a Frank-Sterling mechanism. In this way, the cardiac muscle behaves somewhat like an elastic band - the more extended it generates the more "pressure". However, if the heart muscle is overextended or if the heart is repetitively extended over a large period REF'177833, it eventually loses its "pressure" and becomes flaccid (a form of remodeling). The remodeling progresses in stages. After a heart attack or as a consequence of heart disease, the heart becomes rounder and larger. The heart muscle cells die and the heart like a pump becomes weaker. If remodeling is allowed to progress, the heart's main pumping chamber - the left ventricle - enlarges and changes in shape, becoming round. The heart also suffers from changes in the cellular level. The heart is divided into the right side and the left side. The right side, which includes the atrium or atrium and the right ventricle, collects and pumps the deoxygenated blood to the lungs to collect oxygen. The left side, which includes the atrium or atrium and the left ventricle, collects and pumps oxygenated blood to the body. Oxygen deficient blood returns from the body enters the right atrium through the vena cava. The right atrium contracts, pushing blood through the tricuspid valve and into the right ventricle. The right ventricle contracts to pump blood through the pulmonary valve and into the pulmonary artery, which connects to the lungs.The blood picks up oxygen in the lungs and then travels back to the heart through the pulmonary veins. The pulmonary veins empty into the left atrium, which contracts to push the oxygenated blood into the left ventricle.The left ventricle contracts, which pushes the blood through the aortic valve and into the aorta, which connects The heart's own pacemaker is located in the atrium and is responsible for the start of the heartbeat.The heartbeat starts with the heart, the coronary arteries that extend from the aorta provide the blood of the heart. Activation of the atrial tissue in the region of the pacemaker (ie, the sinoatrial or "SA" node), followed by cell-to-cell excitation of excitation throughout the atrium. The normal excitable tissue link that connects the atria to the ventricles is the atrioventricular (AV) node located at the border between the atria and the ventricles. Propagation takes place at a slow rate, but at the ventricular end the bundle of His (that is, the electrical conduction path located in the ventricular septum) and nodules of fascicles carry excitation to many sites in the right and left ventricle at a relatively high speed of 1-2 m / s. Slow conduction at the AV junction results in a delay of about 0.1 seconds between atrial and ventricular excitation. This synchronization facilitates the terminal filling of the ventricles from the atrial contraction before the ventricular contraction. After the AV node is encouraged, the fascicle of His separates into two ramifications of fascicles (left and right) which propagate along each of the septa. The fascicles branch into Purkin fibers that are distributed to the inner sides of the ventricular walls. This ensures the propagation of excitatory pulses within the ventricular conduction system that proceeds at a high relative velocity when compared to propagation through the AV node. The "heart failure" syndrome is a common course for the progression of many forms of heart disease. Heart failure can be considered to be the condition in which an abnormality of cardiac function is responsible for the heart's inability to pump blood at a rate commensurate with the requirements of the metabolizing tissues, or it can do so only at a pressure of abnormally high fill. Typically, high filling pressures result in dilation of the left ventricular chamber. The etiologies that can lead to this form of failure include idiopathic cardiomyopathy, viral cardiomyopathy, and ischemic cardiomyopathy. Heart failure is a chronic condition that affects more than five million Americans, and is the most common reason for hospitalization among the elderly. Contrary to its name, heart failure is not a heart attack. Nor is it the sudden stop of the heart that is beating. Heart failure means that the heart is failing to pump enough blood to meet the body's needs. This often occurs in patients whose hearts have been thinned or damaged by a heart attack or other conditions. As soon as the heart continues to fail, patients may experience breathing deficiency, fluid accumulation in the extremities and severe fatigue. The delays in response of the septum to the excitatory impulse can cause contractions that are not simultaneous and therefore the pattern of ventricular contraction is non-concentric. In this mode, the heart is beating inefficiently. When the heart is working properly, both lower chambers (ventricles) pump at the same time and in synchrony with the pumping of the two upper chambers
(atria) Up to 40 percent of patients with heart failure, however, have disturbances in the conduction of electrical impulses to the ventricles (for example, blockage of bundle branchings or intraventricular conduction delay). As a result, the left and right ventricles are activated at different times. When this happens, the walls of the left ventricle (the chamber responsible for pumping blood throughout the body) do not contract simultaneously, reducing the efficiency of the heart like a pump. The heart typically responds by beating faster and dilating. This results in a vicious cycle of additional delay, constriction of the vessels in the body, retention of salt and water, and also worsening of heart failure. These driving delays do not respond to antiarrhythmics or other drugs. Patients who have heart failure may be candidates for a pacemaker. A biventricular pacemaker is a type of implantable pacemaker designed to treat heart failure. A biventricular pacemaker can help to synchronize the lower chambers by sending the electrical signals simultaneously to the left ventricle and the right ventricle. By stimulating both ventricles (biventricular control), the pacemaker causes the pump walls of the right and left ventricles to pump together again. The heart is thus resynchronized, pumping more efficiently while causing less wear and tear in the heart muscle by itself. This is because the biventricular pacemaker is also referred to as cardiac resynchronization therapy (CRT). For patients suffering from heart failure, remodeling of the heart may occur. The remodeling associated with heart failure is characterized by enlargement of the left ventricle of the heart. In addition, the left ventricle becomes thinner. There is an increased use of oxygen, a higher degree of regurgitation of the mitral valve, and a decreased ejection fraction. The remodeling sets a "domino effect" of additional damage to the heart cells and more severe heart disease. The biventricular pacemaker of the present invention can potentially reverse the process. This beneficial effect on the heart is called "reverse remodeling". Typical biventricular pacemakers use 2.5 volt cathode pulses in the atrium and 5 volts in the ventricle. Heart attack A heart attack is an event that results in permanent damage or cardiac death. It is also known as a myocardial infarction, since part of the cardiac muscle (myocardium) can literally die (infarction). A heart attack occurs when one of the coronary arteries becomes severely or totally blocked, usually by a blood clot. When the heart muscle does not get the oxygenated blood it needs, it will die. The severity of a heart attack usually depends on how much of the heart muscle is damaged or dies during a heart attack.Although a heart attack is usually the result of a number of chronic heart conditions (for example coronary artery disease), the drive for a heart attack is often a blood clot that has blocked the flow of blood through a coronary artery.If the artery has already been narrowed by a fatty plaque (a disease called atherosclerosis), the blood clot may be large enough to block blood flow severely or completely.The victim may experience an episode of cardiac ischemia, which is a condition in which the heart is not giving enough oxygenated blood.This is often accompanied by angina (a type of chest pain). , pressure or discomfort), although silent ischemia shows no signs at all. Cardiac ischemia argos can trigger a heart attack. Depending on the severity of both the attack and the subsequent tear, a heart attack can lead to the following: • heart failure, a chronic condition in which at least one heart chamber is not pumping well enough to meet the demands of the body. • The electrical instability of the heart, which can cause a potentially dangerous abnormal heart rhythm (arrhythmia). • Cardiac arrest, in which the heart stops beating at the same time, resulting in early cardiac death in the absence of immediate medical attention. • Cardiogenic shock, a condition in which the damaged heart muscle can not pump normally and enters a shock-like state that is frequently fatal. • death Whether the heart muscle will continue to function or not after a heart attack depends on how much of it is damaged or how much of it dies before the patient can get medical treatment. The location of damage to the heart muscle is also important. Since different coronary arteries supply different areas of the heart, the severity of the damage will depend on the degree to which the artery is blocked and the amount and area of the heart muscle that depends on that blocked artery. As indicated previously, the tissue that is damaged by the coronary attack does not respond or responds slower than the normal speed to excitatory impulses. Healthy tissue operates normally, but as a consequence it places increased tension on this marginalized tissue, thereby "spreading" it. It is desirable to treat a coronary attack in order to minimize the likelihood of continued damaging remodeling. This can be done by reducing the contraction resistance of healthy cardiac tissues, by increasing the resistance of the contraction of marginalized cardiac tissue, or by implementing a combination of both therapies. Coronary disease and arrhythmia The disease that affects the AV junction may result in interference with normal AV conduction. This is described by different degrees of blockage. In a first degree block this conduction simply decreases, in the second degree blockade there is a periodic fallen heartbeat, but in the third degree blockade no signal reaches the ventricles. This last condition is also referred to as a complete heart block. In this case the ventricles are completely decoupled from the atria. While the coronary velocity of the atrium is still determined in the AV node, the ventricles are excited by ectopic ventricular sites. Because under normal conditions the ventricles are driven by the atria, latent ventricular pacemakers must have a lower speed. Consequently, in the complete coronary block, the ventricles beat at a low speed (bradycardia). Even this condition may not require medical attention, but if the heart rate is very low, a condition known as Stokes-Adams syndrome, the situation comes to endanger life. The prognosis in the case of complete heart block and Stokes-Adams is 50% mortality within one year. In this case the implantation of an artificial pacemaker is mandatory. Another condition, known as the syndrome of sinudal disease, is also one for which the artificial pacemaker is the treatment of choice. Under these conditions, bradycardia results from atrial velocity that is abnormally low. In this way, although the AV junction is normal, the ventricles are operated at a very low speed. A wide variety of arrhythmias can occur after acute myocardial infarction. Supraventricular tachyarrhythmias, including sinus tachycardia, atrial fibrillation, and atrial flutter, are relatively common and generally do not endanger life. Ventricular arrhythmias have a high incidence: premature ventricular beats occur in up to 90% of patients, ventricular tachycardias in up to 40% of patients, and ventricular fibrillation in up to 5%. Ventricular fibrillation is more common in the first 24 to 48 hours after myocardial infarction and is life-threatening. Although non-sustained ventricular tachycardia is of prognostic significance in the postinfarction period, it is not true whether therapy will alter the prognosis. Conduction abnormalities and bradyarrhythmias, also frequent complications of acute myocardial infarction, require pacemaker therapy when they are symptomatic. The temporary pacemaker is typically used first. If symptoms persist, a permanent pacemaker may be necessary. A pacemaker is an artificial device to electrically assist in the pacemaker of the heart so that the heart can pump blood more effectively. Implantable electronic devices have been developed to treat abnormally slow heart rates (bradycardia) and excessively rapid heart rates (tachycardia). The work of the pacemaker is to maintain a safe heart rate by properly supplying the pump chambers with the synchronized electrical impulses that replace the heart's normal rhythmic impulses. The device designed to perform this life sustaining role consists of an energy source the size of a silver dollar (containing the battery), and control circuits, wires or "conductors" that connect the power source to the Heart chambers The conductors are typically placed in contact with the "right atrium or right ventricle, or both, which allow the pacemaker to detect and stimulate in various combinations, depending on where control is required.
The absence of an arrhythmia diagnosis is not typically used as an anti-arrhythmic pacemaker as a treatment for the victims of myocardial infarction. Whether a myocardial infarction leads to heart failure depends mostly on how the remaining normal heart muscle behaves. The process of ventricular dilation (remodeling) is usually the result of chronic volume that overloads or specifically damages the myocardium. At a normal speed that is exposed to increased cardiac output requirements in the long term, for example, that of an athlete, there is an adaptive process of slight ventricular dilation and hypertrophy to the muscle myocyte. In this way, the heart fully compensates for the increased cardiac output requirements. With the damage to myocardial or chronic volume overload, however, there are increased requirements placed on the contracting myocardium to such a degree that this compensated state is never achieved and the heart continues to expand. The basic problem with a large dilated left ventricle is that there is a significant increase in wall tension and / or tension both during diastolic filling and during systolic contraction. In a normal heart, the adaptation (or remodeling) of muscle hypertrophy (thickening) and ventricular dilatation maintain a nearly constant wall tension for systolic contraction. However, in a failing heart, the initiating dilation is greater than the hypertrophy and the result is an increased wall tension requirement for the systolic contraction. This is felt to be an initial insult to the muscle myocyte which results in additional muscle damage. The increase in wall tension is also true for diastolic filling. Additionally, due to the lack of cardiac output, there is generally an increase in ventricular filling pressure from several physiological mechanisms. On the other hand, in diastolic there is both an increase in diameter and an increase in pressure over normal, both of which contribute to higher wall tension levels. The increase in diastolic wall tension is felt to be the primary contributor to initiate dilation of the chamber. The inadequate pumping of blood into the arterial system by the heart is sometimes referred to as "forward failure" with "backward failure" with reference to the resulting elevated pressures in the lungs and systemic veins that lead to congestion. Failure to reverse is the natural consequence of forward failure since blood in the pulmonary and venous systems fail to be pumped. The forward failure can be caused by impaired contractility of the ventricles or by an increased posterior load (i.e., forces resisting blood rejection) due, for example, to systemic hypertension or valvular dysfunction. A physiological compensatory mechanism that acts to increase cardiac output is due to backward failure which increases the diastolic filling pressure of the ventricles and therefore increases the preload (ie, the degree to which the ventricles are narrowed by the volume of blood in the ventricles at the end of diastole). An increase in preload causes an increase in infarct volume during systole, a phenomenon known as the Frank-starling principle. In this way, heart failure can be at least partially compensated by this mechanism but at the expense of possible pulmonary and / or systemic congestion. When the ventricles are stretched due to the increased preload over a period of time, the ventricles become dilated. Enlarged ventricular volume causes increased ventricular wall tension at a given systolic pressure. Together with the increased pressure volume work done by the ventricle, this acts as a stimulus for hypertrophy of the ventricular myocardium that leads to alterations in cellular stress, a process referred to as ventricular remodeling. Hypertrophy may increase systolic pressures but it also decreases compliance of the ventricles and therefore increases diastolic filling pressure to result in even more congestion. It has also been shown that the sustained stresses that cause hypertrophy can induce apoptosis (ie, programmed cell death) of cardiac muscle cells and eventual thinning of the wall which also causes deterioration in cardiac function. In this way, although ventricular dilation and hypertrophy can first be compensatory and increase cardiac output, the process ultimately results in both systolic and diastolic dysfunction. It has been shown that the degree of ventricular remodeling is positively correlated with increased mortality in patients with CHF. Over the past few years, numerous randomized clinical trials have been completed and show that the two classes of drugs can significantly improve the overall survival of patients who have signs of impaired heart failure (either low left ventricular rejection fraction or increased ventricular dilation). ). These drugs are beta blockers and ACE inhibitors. Beta blockers work by blocking the effect of adrenaline on the heart, and have been noted to have numerous beneficial effects in various types of coronary heart disease. Beta blockers reduce the risk of angina in patients with coronary artery disease, significantly improving the survival of patients with heart failure, significantly reducing the risk of sudden death in patients after heart attacks, and seems to delay or prevent remodeling seen in the ventricle left after heart attacks. However, patients with severe asthma or other lung disease simply can not safely take these drugs. ACE inhibitors block the enzyme that converts angiotensin, and therefore produces numerous salutary effects in the cardiovascular system. This class of drugs significantly improves the long-term survival among survivors of acute myocardial infarction, and also reduces the incidence of heart failure (apparently by preventing or delaying remodeling), recurrent heart attacks, stroke, and sudden death. While the use of drugs can be beneficial, after a myocardial infarction the undamaged area of the heart is still required to work harder and the tissue damaged by the infarct remains uncured. What would be truly useful is to provide alternative methods to treat "heart failure and post-myocardial infarction conditions that will reduce or prevent adverse remodeling and allow damaged tissue to be cured." Such alternative methods may be provided instead of, or together With, conventional pharmaceutical therapies and with new tissue regeneration therapies SUMMARY OF THE INVENTION One embodiment of the present invention provides a method for treating the heart after myocardial infarction (MI). provided to selected portions of the heart regardless of whether an arrhythmia diagnosis has been made.The stimulation may be in the form of excitatory or non-excitatory pulses using cathode, anode and biphasic waveforms.The portions of the heart selected for stimulation are determined selected based on the type of stimulation to be administered and the degree of damage sustained by the cardiac tissue. In one embodiment of the example, only healthy heart tissue is stimulated. In an alternative embodiment of the present invention, the marginal heart tissue can also be stimulated in such a way that the heart beats in a more balanced way. In an example embodiment, biphasic, biventricular stimulation is directed to undamaged areas of the heart to increase muscle contraction of healthy tissue thereby allowing the heart to achieve normal or near normal function. Increased muscle contraction of the stimulated portion of the heart reduces non-uniform heart loading and avoids or reduces the adverse forms of remodeling of the heart after myocardial infarction. The biventric, biventricular stimulation of the exemplary embodiment of the present invention comprises continuous application of both cathode and anodic impulses to the right and left ventricles through the electrodes that contact the undamaged portions of the heart. In one embodiment of the present invention, unless the pacemaker is used to control arrhythmias, the non-excitatory biphasic stimulation is not applied to the heart in response to the sensitization of an indicated cardiac signal from an arrhythmia. Moreover, non-excitatory biphasic stimulation is applied continuously to allow the heart to compensate for cardiac tissue affected by MI while avoiding undesirable forms of remodeling. Optionally, the application of biphasic stimulation is synchronized to coincide with an initiation of a depolarization wave as determined by cardiac detectors. Additionally, stimulation of the example modality can be combined with germ cell implantation at sites where the heart tissue has been damaged. Germinal cell therapy regenerates damaged heart tissue in such a way that, over time, stimulation therapy can be completed.
In this exemplary embodiment of the present invention, the prevention of adverse remodeling germinations from a number of mechanisms. The biventricular pacemaker effect provides increased inotropic effect while at the same time reducing the oxygen demand and consumption by the heart, and reduces and equalizes the wall tension, in effect it reduces the tendency to extend the damaged areas of the heart. Also, the stimulus for germ cell implantation and proper orientation depends on an appropriate wall tension and electrical activity on the damaged area. These conditions are properly established by this treatment. Additionally, exposure of damaged heart tissue to an electrical current can directly heal damaged areas. This is similar to the use of currents of appropriate polarity to cure other tissues such as fractures of bone and skin incisions. As will be appreciated by those skilled in the art, the description of example modalities is not limited. While biventric, biventricular stimulation is described herein, other waveforms and stimulation sites can be employed to reduce the development burden on undamaged cardiac tissue and thereby allow the heart to reverse or prevent undesirable remodeling. . Additionally, therapies can be used.
excitatory or non-excitatory impulses. As previously noted, the tissue that is damaged by the heart attack does not respond or responds slower than the normal speed to excitatory impulses. Healthy tissue places the increased tension on this marginalized tissue, thus "spreading" it. It is desirable to treat the heart attack in order to minimize the likelihood of continued harmful remodeling. This can be done by reducing the contraction resistance of healthy cardiac tissues, by increasing the contraction resistance of marginalized cardiac tissue, or by implementing a combination of both therapies. It is therefore an aspect of the present invention to promote the healing of cardiac tissue affected by an MI. It is another aspect of the present invention to increase the cardiac output of cardiac tissue not affected by MI through more coordinated cardiac contraction leading to a greater shock volume with less required cardiac work. It is yet another aspect of the present invention to stimulate the marginal areas of cardiac tissue in such a way that they contract to some degree to more balanced operation of the cardiac MI post. It is yet another aspect of the present invention to apply a combination of stimulation to tissue that is damaged and to tissue that is not damaged by an MI to promote the balanced functioning of post-MI cardiac tissue.
It is yet another aspect of the present invention to reduce the adverse forms of remodeling of the heart after MI. It is yet another aspect of the present invention to continuously stimulate the heart selection portions unaffected by an MI using stimulation pulses. It is a further aspect of the present invention to promote the healing of cardiac tissue affected by an MI using germ cells. It is still another aspect of the present invention to maintain the tension of the wall in the heart at acceptable levels in patients suffering from heart disease. It is a further aspect of the present invention to promote the normalization of wall tensions thereby promoting the implantation of damaged germ cells in tissue. These and other aspects of the present invention will be apparent from the general and detailed description that follows. According to one embodiment of the present invention, an apparatus for minimizing cardiac remodeling of an arrhythmic river patient comprises a cardiac stimulation device, a group of left ventricular electrodes, and a group of right ventricular electrodes. The group of left ventricular electrodes comprises LV electrodes attached to the left ventricle at increased distances from the AV node. The right ventricular electrode group comprises the RV electrodes attached to the left ventricle at increased distances from the AV node. The cardiac stimulation device is adapted to stimulate healthy and compromised areas of cardiac tissue. The cardiac stimulation device joins the LV and RV electrodes and generates a synchronized signal coinciding with a refractory period. In response to the synchronization signal, the cardiac stimulation device sends pulses to the LV and RV electrodes sequenced in such a way that an initial pulse arrives at an LV electrode and at an RV electrode closer to the AV junction and subsequent impulses arrive at an LR and RV electrode progressively also from the AV junction. In one embodiment of the present invention, the impulse is excitatory. In another embodiment of the present invention, the impulse is not excitatory. In yet another embodiment of the present invention, the impulse is biphasic. According to one embodiment of the present invention, the biphasic pulse comprises a first stimulation phase having a first phase polarity, a first phase amplitude, a first phase conformation, and a first phase duration, in order to recondition the myocardium to accept the subsequent stimulation. The biphasic pulse further comprises a second stimulation phase having a second phase polarity, a second phase amplitude that is greater in absolute value than the first phase amplitude, a second phase conformation, and a second phase duration. In one embodiment of the present invention, the first phase polarity is positive, and the second phase polarity is negative. In still another embodiment of the present invention, the first phase amplitude is at a maximum subthreshold amplitude. In one embodiment of the present invention, the germ cells are deposited in cardiac tissue. In one embodiment of the present invention, the LV and RV electrodes are located in such a way as to electrically stimulate the compromised area of cardiac tissue in which the germ cells have been deposited. In an alternative embodiment of the present invention, the LV and RV electrodes are located so as to preclude electrical stimulation of the compromised area of cardiac tissue in which the germ cells have been deposited. According to one embodiment of the present invention, an apparatus for minimizing cardiac remodeling of a non-arrhythmic patient comprises a cardiac stimulation device, a group of left ventricular electrodes, a group of right ventricular electrodes and a detector. The detector detects the excitation of a cardiac chamber. The group of left ventricular electrodes comprises LV electrodes attached to the left ventricle at increased distances from the AV node. The right ventricular electrode group comprises RV electrodes attached to the left ventricle at increased distances from the AV node. The cardiac stimulation device is adapted to stimulate healthy and compromised areas of cardiac tissue. The cardiac stimulation device joins the LV and RV electrodes and the detector. In response to a signal from the detector, the cardiac stimulation device sends pulses to the LV and RV electrodes sequenced such that an initial pulse arrives at an LV electrode and an RV electrode closest to the AV junction and the impulses Subsequent arrives at an LR electrode and at a progressively additional RV electrode of the AV junction. In one embodiment of the present invention, the impulse is excitatory. In another embodiment of the present invention, the impulse is not excitatory. In yet another embodiment of the present invention, the impulse is biphasic. According to one embodiment of the present invention, the biphasic pulse comprises a first stimulation phase having a first phase polarity, a first phase amplitude, a first phase conformation, and a first phase duration, in order to precondition the myocardium to accept the subsequent stimulation. The biphasic pulse further comprises a second stimulation phase having a second phase polarity, a second phase amplitude that is greater in absolute value than the first phase amplitude, a second phase conformation, and a second phase duration. In an embodiment of the present invention, the first phase polarity is positive, and the second phase polarity is negative. In still another embodiment of the present invention, the first phase amplitude is at a maximum subthreshold amplitude. In one embodiment of the present invention, the germ cells are deposited in cardiac tissue. In one embodiment of the present invention, the LV and RV electrodes are positioned to electrically stimulate the compromised area of cardiac tissue in which the germ cells have been deposited. In an alternative embodiment of the present invention, the LV and RV electrodes are located so as to preclude electrical stimulation of the compromised area of cardiac tissue in which the germ cells have been deposited. One embodiment of the present invention provides a method for minimizing cardiac remodeling of a non-arrhythmic patient. The germ cells are administered to a myocardial infarction (MI) of a patient.
Biphasic biventricular stimulation is continuously administered to cardiac tissue outside the MI area. According to one embodiment of the present invention, the biphasic pulse comprises a first stimulation phase having a first phase polarity, a first phase amplitude, a first phase conformation, and a first phase duration, in order to precondition the myocardium to accept the subsequent stimulation. The biphasic pulse further comprises a second stimulation phase having a second phase polarity, a phase amplitude that is larger in absolute value than the first phase amplitude, a second phase conformation and a second phase duration. In one embodiment of the present invention, the first phase polarity is positive, and the second phase polarity is negative. In still another embodiment of the present invention, the first phase amplitude is at a maximum subthreshold amplitude. In one embodiment of the present invention, the germ cells are deposited in cardiac tissue. In one embodiment of the present invention, the LV and RV electrodes are positioned to electrically stimulate the compromised area of cardiac tissue in which the germ cells have been deposited. In an alternative embodiment of the present invention, the LV and RV electrodes are positioned so as to preclude electrical stimulation of the compromised area of cardiac tissue in which the germ cells have been deposited. According to one embodiment of the present invention, an apparatus for minimizing cardiac remodeling of a non-arrhythmic patient comprises a cardiac stimulation device, a group of left ventricular electrodes, a group of right ventricular electrodes, and a detector. The detector detects the excitation of a cardiac chamber. The group of left ventricular electrodes comprises LV electrodes attached to the left ventricle at increased distances from the AV node. The right ventricular electrode group comprises RV electrodes attached to the left ventricle at increased distances from the AV node. The cardiac stimulation device is adapted to stimulate healthy and compromised areas of cardiac tissue. A compromised area of the heart has germinal cells deposited therein. The heart stimulation device joins the LV and RV electrodes and the detector. In response to a detector signal, the heart stimulation device sends pulses to the LV and RV electrodes sequenced such that an initial pulse arrives at the LV electrode and at the RV electrode closest to the AV junction and subsequent impulses arrive progressively in addition to the AV junction in an LR and RV electrode.
In one embodiment of the present invention, the germ cells are deposited in cardiac tissue. In one embodiment of the present invention, the LV and RV electrodes are positioned to electrically thereby stimulate the compromised area of cardiac tissue in which the germ cells have been deposited. In an alternative embodiment of the present invention, the LV and RV electrodes are located so as to preclude electrical stimulation of the compromised area of cardiac tissue in which the germ cells have been deposited. Figure 1 illustrates a heart with multiple ventricular electrodes that are connected to external surfaces of the ventricles, and include a separate electrode each indicated for the right and left ventricles according to the embodiments of the present invention. Figure 2 is a schematic representation of a conductive anodic biphasic stimulation according to an embodiment of the present invention. Figure 3 is a schematic representation of low-level long-term conductive anodic stimulation, followed by cathodic stimulation according to one embodiment of the present invention: Figure 4 is a schematic representation of low level conductive anodic stimulation and Long duration, followed by cathodic stimulation according to one embodiment of the present invention. Figure 5 is a schematic representation of short-term conductive anodic stimulation and short duration administered in series, followed by cathodic stimulation according to an embodiment of the present invention. One embodiment of the present invention provides a method for treating the heart after myocardial infarction (MI). Electrical stimulation is provided to selected portions of the heart independently if a diagnosis of some arrhythmia has been given. The stimulation may be in the form of excitatory or non-excitatory pulses using cathodic, anodic and biphasic waveforms. The portions of the heart selected for stimulation are selected based on the type of stimulation to be administered and the degree of damage sustained by the cardiac tissue. In an example embodiment, only healthy cardiac tissue is stimulated. In an exemplary embodiment of the present invention, the biventricular, biphasic stimulation of the present invention is directed to undamaged areas of the heart to increase muscle contraction of healthy tissue by itself allowing the heart to achieve normal or near-normal functioning. The increased muscle contraction of the stimulated portion of the heart reduces the load on the heart and prevents, prevents or reduces the adverse forms of remodeling of the heart after a myocardial infarction. Biventricular, biphasic stimulation involves the continuous application of both the cathode and anodic impulses simultaneously to the right and left ventricles through the electrodes that contact undamaged portions of the heart. In one embodiment of the present invention, unlike the pacemaker that is used to control arrhythmias, biphasic stimulation does not apply to the heart in response to detecting a cardiac signal indicative of an arrhythmia. Furthermore, biphasic stimulation is applied continuously to allow the heart to compensate for the cardiac tissue affected by an MI while avoiding undesirable forms of remodeling. Optionally, the application of biphasic stimulation is synchronized to coincide with the onset of a depolarization wave as determined by cardiac detectors. Additionally, the biphasic stimulation of the example modality is combined with the implantation of germ cells at sites where cardiac tissue has been damaged. Germ cell therapy regenerates damaged heart tissue so that over time, biphasic stimulation therapy can be terminated. With reference to Figure 1, a diagram of the heart illustrates the four chambers: right atrium (RA), left atrium (LA), right ventricle (RV) and ventricle left (LV for its acronym in English). The electrode conductor 201, connected to the group of electrodes RV 201A which comprises the individual electrodes 202, 204, 206, 208 and 210, is shown with the individual electrodes connected to multiple points on the outer surfaces of the right ventricle. The conductor of the electrode 301, connected to the electrode group LV 3OÍA which comprises the individual electrodes 302, 304, 306, 308 and 310, is shown with the individual electrodes connected to multiple points on the outer surfaces of the left ventricle. While the group of electrodes RV 201A and the group of electrodes LV 3 OIA are illustrated with five electrodes per group, this is not understood as a limitation. Other group sizes may be used without departing from the scope of the present invention. In alternative embodiments, the locations of the individual electrodes in Figure 1 (202, 204, 206, 208 and 210 and 302, 304, 306, 308 and 310) are selected to avoid stimulation of damaged cardiac tissue such as, for example,, damaged tissue as a result of an MI. In yet another embodiment of the present invention, the pulses are applied to the electrodes in order to mimic the normal physiological flow of the normal ventricular depolarization wave. In this modality, the areas closest to (or in) the A-V node are first stimulated during a given beat. In one embodiment of the present invention, the atrial excitation is sensitized (PQ interval) or the ventricular excitation is sensitized (QRS interval) and an external excitatory pulse is applied to the first electrode (after an appropriate delay) to coincide with the start of the ventricular depolarization wave. The subsequent excitatory impulses are directed to areas progressively in addition to the A-V node. The intermediate areas between these two extremes are appropriately stimulated on a scaled time base which, again, mimics the normal intrinsic conduction trajectories that facilitate the most efficient cardiac contraction. In one embodiment of the present invention, the pulses are applied to healthy cardiac tissue that is not affected by the MI, thereby allowing the damaged tissue to heal and the stimulation voltage to be low. This progressive stimulation modality requires specific knowledge of the placement of each electrode in relation to another electrode, as well as the placement in relation to the electrical conduction trajectories in the heart. In this way, it is appropriate to contemplate "classes" of electrodes, in which, for example, the electrodes are identified or categorized according to when they are burned. In a simplistic five-plane system, for example, the first planar electrodes are designed as the first to be burned (ie, the electrodes closest to the AV node), followed successively (and temporarily progressively according to the trajectories of normal conduction) by the second, third, fourth and fifth plane electrodes, where the fifth plane electrode may be the last to be ignited, and those locations in the ventricle may correspond to the last areas to be depolarized in the course of a contraction / normal ventricular beat An even simpler plane system (ie two, three or four) can be used, or one more complex (ie, one with more than 5 planes, or with only another electrode positioning base, such as a similar arrangement honeycomb in a particular area with a known or suspected pathology such as rhythmicity, reentry, conduction, contractility, etc. Additionally, multiple electrodes within a given plane may be enumerated or otherwise identified in a manner other than such. Thus, the practitioner can test and use electrodes with respect to known locations in the heart, for example, to anticipate and / or derive an electrical "" blocking area. "In this" "mode, small, multiple electrodes are pulsed with impulses. excitatory in a physiological sequential manner In yet another embodiment of the present invention, the technique described above for stimulating the ventricles is applied to the atrium. The electrodes are progressively placed from the close to the SA node (first to be burned) to approach the AV node (last to be burned), mimicking the normal intrinsic conduction trajectories of the atrium. Deriving an area of damaged tissue is also anticipated by the present invention, and can be effected by first identifying such areas, for example, by determining myocardial resistance values between the electrodes. The electrical impulses are then routine to those areas to the myocardium with appropriately low resistances, then as nearly as possible as the conduction lines of the normal intrinsic conduction paths. The communication of, and control of, resistance measurements between electrodes, as well as developing a referral protocol for a particular patient may be effected by an external computer. The external computer can communicate with the pacemaker by any convenient method, for example, radiotelemetry, direct coupling (such as by connecting an external wire from the pacemaker to the surface of the patient's skin), etc. Figures 2 to 5 represent a range of biphasic stimulation protocols. These protocols have been described in U.S. Patent 5,871,506 to Mower, which is incorporated herein by reference in its entirety. Figure 2 represents the biphasic electrical stimulation in which a first stimulation pass which comprises the anodic stimulus 202 is administered with the amplitude 204 and a duration 206. The first stimulation phase is immediately followed by a second stimulation phase which it comprises the cathodic stimulus 208, which is of equal intensity and duration to that of the anodic stimulus 202. Figure 3 represents the biphasic electrical stimulation wherein a first phase of stimulation is administered which comprises the low level, long-lasting anodic stimulation. 302 which has the amplitude 304 and the duration 306. This first stimulation phase is immediately followed by a second stimulation phase which comprises the cathodic stimulation 308 of intensity and conventional duration. In an alternative embodiment of the invention, the anodic stimulation 302 is at maximum subthreshold amplitude. In yet another alternative embodiment of the invention, the anodic stimulation 302 is less than three volts. In another alternative embodiment of the invention, the anodic stimulation 302 is a duration of about two to eight milliseconds. In yet another alternative embodiment of the invention, cathode stimulation 308 is of short duration. In another alternative embodiment of the invention, the cathodic stimulation 308 is approximately 0.3 to 1.5 milliseconds. In yet another alternative embodiment of the invention, cathodic stimulation 308 is of high amplitude. In another alternative embodiment of the invention, the cathodic stimulation 308 is in the approximate range of three to twenty volts. In yet another alternative embodiment of the present invention, cathodic stimulation 308 is of a duration less than 0.3 milliseconds and at a voltage greater than twenty volts. In another alternative embodiment, anodic stimulation 302 is administered over 200 milliseconds after heartbeat. In the manner described by these modalities, as well as those alterations and modifications which may become obvious upon reading this specification, a maximum membrane potential without activation is achieved in the first phase of stimulation. Figure 4 depicts biphasic electrical stimulation wherein a first stimulation phase which comprises anodic stimulation 402 is administered over a period 404 with an increased intensity level 406. The ramp of intensity level increase 406 may be linear or not linear, and the slope may vary. This anodic stimulation is immediately followed by a second phase of stimulation which comprises the 408 cathodic stimulation of intensity and conventional duration. In an alternative embodiment of the invention, anodic stimulation 402 is increased to a maximum subthreshold amplitude. In yet another alternative embodiment of the invention, anodic stimulation 402 is increased to a maximum amplitude that is less than three volts. In another alternative embodiment of the invention, anodic stimulation 402 is a duration of about two to eight milliseconds. In yet another alternative embodiment of the invention, cathodic stimulation 408 is of a short duration. In another alternative embodiment of the invention, the cathodic stimulation 408 is approximately 0.3 to 1.5 milliseconds. In yet another alternative embodiment of the invention, cathodic stimulation 408 is of high amplitude. In another alternative embodiment of the invention, the cathodic stimulation 408 is in the approximate range of three to twenty volts. In yet another alternative embodiment of the present invention, cathodic stimulation 408 is of duration less than 0.3 milliseconds and at a voltage greater than twenty volts. In another alternative modality, the anodal stimulation 402 is administered over 200 milliseconds after the heartbeat. In the manner described by these modalities as well as alterations and modifications which may become obvious upon reading this "specification, a potential maximum membrane without activation is achieved in the first phase of stimulation." Figure 5 represents electrical stimulation. biphasic wherein a first phase of stimulation which comprises a series 502 of anodic impulses is administered in the amplitude 504. In a modality the rest period 506 is of equal duration to the stimulation period 508 and is administered in the baseline amplitude In an alternative embodiment, rest period 506 is of a different duration than stimulation period 508 and is administered in the baseline amplitude.Relayment period 506 occurs after each stimulation period 508 with the exception that a second phase of stimulation which includes the cathodic stimulation 510 of conventional intensity and the duraci The ion immediately follows the completion of the 502 series. In an alternative embodiment of the invention, the total charge transferred through the 502 series of the anodic stimulation is at the maximum subthreshold level. In yet another alternative embodiment of the invention, the first stimulation pulse of the 502 series is administered over 200 milliseconds post heartbeat. In another alternative embodiment of the invention, cathodic stimulation 510 is approximately 0.3 to 1.5 milliseconds. In another alternative embodiment of the invention, the cathodic stimulation 510 is of a high amplitude. In yet another alternative embodiment of the invention, the cathodic stimulation 510 is in the approximate range of three to twenty volts. In another alternative embodiment of the invention, the cathodic stimulation 510 is of a duration less than 0.3 milliseconds and at a voltage greater than twenty volts. The individual pulses of the series of the pulses can be square waves, or can be of any other form, for example, the pulses which decay linearly or curvilinearly from an initial subthreshold amplitude, to a lower amplitude. In the biphasic stimulation protocol practiced by the present invention, the magnitude of the anodic phase does not exceed the maximum threshold amplitude. The anodic phase serves to precondition the stimulated myocardium, thus decreasing the excitation threshold in such a way that the cathodic excitation of less intensity than normal will produce depolarization leading to contraction. The pacemaker and the subsequent normalization of wall tensions promotes the implantation of germ cells in damaged tissue, and guides their proper orientation during cell maturation. The values of duration and amplitude will depend on factors such as placement / position of the particular electrode (including, for example, whether the electrode is in pure muscle tissue "against specialized conductive tissue or pacemaker), whether the tissue is damaged / scarred is in close proximity to the electrode, electrode depth within the tissue, local tissue resistance, presence or absence of any of a long range of local pathologies, etc. However, typical anodic phase durations often fall within the range from about two milliseconds to about eight milliseconds, while typical cathodic durations often fall within the range of about 0.3 milliseconds to about 1.5 milliseconds.The typical anodic phase amplitudes (most commonly in the maximum subthreshold amplitude) often fall within from the range of approximately 0.5 volts to 3.5 volts, compared to typical cathode phase amplitudes of about 3 volts to about 20 volts. Since the heart is constantly stimulated, the impulses of the pacemaker are applied without the need to demand awareness. In addition, the constant consistent pacemaker decreases the tension in the heart. In another embodiment of the present invention, the damaged tissue is located and treated by inserting or applying the donor or "germ" cells. A means for inserting and a means for applying the germ cells to damaged cardiac tissue is described in "U.S. Patent Application No. 60 / 429,954, entitled" Method and Apparatus for Cell and Electrical Therapy of Living Tissue " , a utility application for which is presented on November 25, 2003, both applications that are incorporated herein in their entirety for all purposes In one embodiment of the present invention, the damaged tissue is treated and the impulse of the Biventricular pacemaker is applied continuously to functioning portions of the heart In one embodiment, the pacemaker sites are chosen to ensure that the tissue treated with germ cells is not electrically stimulated.In an alternative modality, the pacemaker sites are chosen in such a way that the tissue treated with germ cells receives impulses of electrical stimulation that have an amplitude below that required Rida to excite the tissue of the heart. A system and method for managing harmful cardiac remodeling after a myocardial infarction has been described has been described. It will also be understood that the invention can be exemplified in other specific forms without departing from the scope of the invention described and that the examples and embodiments described herein are in all illustrative and non-restrictive aspects. Those skilled in the art of the present invention will recognize that other embodiments using the concepts described herein are also possible. In addition, any reference to claim elements in the singular, for example, using the articles a, one, or the, is not to be constructed as limiting the element to the singular.
It is noted that in relation to this date, the best method known to the applicant to carry out the aforementioned invention, is that which is clear from the present description of the invention.