Ultrastructure of Purkinje cells in the subendocardium and false tendons in early experimental myocardial infarction complicated by fibrillation in the dog

The effect of regional myocardial ischemia complicated by ventricular fibrillation (VF) on the ultrastructure of subendocardial (SE) and false tendon (FT) Purkinje cells (PC) was studied in anesthetized dogs. In all cases of early ischemia with spontaneous VF, many PC exhibited ultrastructural damage as early as 2 min after the onset of ischemia. The changes noted were: intercalated disk dissociation, sarcoplasmic reticulum vacuolization (SRV), supercontraction, mitochondrial swelling, and sarcolemmal defects (rigor cells). The appearance of at least some rigor PC seemed to precede spontaneous VF, since these cells were absent from the conduction systems in control hearts in which VF was induced by electric shock or reperfusion, from hearts from sham-operated dogs, or from hearts subjected to longer periods of uncomplicated myocardial infarction. These observations indicate that alterations in SE and FTPC may play a role in the pathogenesis of sudden death due to early myocardial ischemia. The mechanism of this rapid damage of PC remains obscure.     

Ultrastructure of Purkinje cells in the subendocardium and false tendons in early experimental myocardial infarction complicated by fibrillation in the dog

The effect of regional myocardial ischemia complicated by ventricular fibrillation (VF) on the ultrastructure of subendocardial (SE) and false tendon (FT) Purkinje cells (PC) was studied in anesthetized dogs. In all cases of early ischemia with spontaneous VF, many PC exhibited ultrastructural damage as early as 2 min after the onset of ischemia. The changes noted were: intercalated disk dissociation, sarcoplasmic reticulum vacuolization (SRV), supercontraction, mitochondrial swelling, and sarcolemmal defects (rigor cells). The appearance of at least some rigor PC seemed to precede spontaneous VF, since these cells were absent from the conduction systems in control hearts in which VF was induced by electric shock or reperfusion, from hearts from sham-operated dogs, or from hearts subjected to longer periods of uncomplicated myocardial infarction. These observations indicate that alterations in SE and FTPC may play a role in the pathogenesis of sudden death due to early myocardial ischemia. The mechanism of this rapid damage of PC remains obscure.     

Sudden cardiac death thirty years ago and at present. The role of autonomic disturbances in acute myocardial infarction revisited

The most common cause of sudden cardiac death is ventricular fibrillation (VF). In addition to the status, size and location of the ventricular focus, a major pathogenic mechanism triggering VF is autonomic dysbalance (disturbance). This term refers to a wide range of reflex changes in the ratio of sympathetic to vagal ventricular activation over time, occurring immediately after coronary artery occlusion at the onset of acute myocardial infarction (AMI). Another trigger of VF is autonomic disturbance due to emotional stress. Experimental and clinical research into autonomic disturbances associated with coronary artery occlusion and emotional stress was given considerable attention as early as some 30 years ago when researchers were already searching for ways of inhibiting autonomic disturbances using predominant sympathetic and vagal activation by beta-blockers (BB) and atropine, respectively. The aim of our paper is to compare results obtained 30 years ago with current status of experimental and clinical research into SCD prevention. Another aim is to identify questions that have remained unanswered to date; answers to these outstanding questions could help further reduce the risk of SCD.     

Repolarization abnormalities and afterdepolarizations in a canine model of sudden cardiac death

Ventricular tachyarrhythmias are the most common cause of sudden cardiac death (SCD); a healed myocardial infarction increases the risk of SCD. We determined the contribution of specific repolarization abnormalities to ventricular tachyarrhythmias in a postinfarction model of SCD. For our methods, we used a postinfarction canine model of SCD, where an exercise and ischemia test was used to stratify animals as either susceptible (VF(+)) or resistant (VF(-)) to sustained ventricular tachyarrhythmias. Our results show no changes in global left ventricular contractility or volumes occurred after infarction. At 8-10 wk postmyocardial infarction, myocytes were isolated from the left ventricular midmyocardial wall and studied. In the VF(+) animals, myocyte action potential (AP) prolongation occurred at 50 and 90% repolarization (P < 0.05) and was associated with increased variability of AP duration and afterdepolarizations. Multiple repolarizing K(+) currents (I(Kr), I(to)) and inward I(K1) were also reduced (P < 0.05) in myocytes from VF(+) animals compared with control, noninfarcted dogs. In contrast, only I(to) was reduced in VF(-) myocytes compared with controls (P < 0.05). While afterdepolarizations were not elicited at baseline in myocytes from VF(-) animals, afterdepolarizations were consistently elicited after the addition of an I(Kr) blocker. In conclusion, the loss of repolarization reserve via reductions in multiple repolarizing currents in the VF(+) myocytes leads to AP prolongation, repolarization instability, and afterdepolarizations in myocytes from animals susceptible to SCD. These abnormalities may provide a substrate for initiation of postmyocardial infarction ventricular tachyarrhythmias.     

New aspects of ICD therapy: from rhythm therapy to complex cardiac monitoring. Development of an implantable, ICD-assisted, intrathoracic 6-channel ECG for continuous monitoring of high infarct risk patients]

Implantable defibrillator systems (ICD) are therapy of choice for the treatment of life-threatening ventricular arrhythmias and in prevention of sudden cardiac death. In more than 80% of patients who receive an ICD, the underlying cardiac disease is a coronary heart disease. Since arrhythmogenic sudden cardiac death can be reliably prevented in these patients by the use of ICD technology, the cardiac prognosis for these patients is determined by the occurrence of myocardial ischemia and myocardial infarction, as well as from the heart failure which develops in consequence. An intrathoracic 6-channel ECG comparable to the standard surface ECG can be reconstructed by further technical development of the electrode configurations currently present in ICD systems. The importance of this development in early diagnosis of myocardial ischemias and myocardial infarction can hardly be adequately estimated at the moment. The chronic consequences of myocardial infarction can be completely prevented or at least greatly reduced by means of such diagnostics and inclusion of immediate initiation of effective, appropriate early therapeutic measures before more serious symptoms even occur. In the development and pilot studies thus far, it has been found that the intrathoracic 6-channel ECG which can be generated in the ICD is capable of reliably recognizing acute myocardial ischemia, irrespective of localization or extent earlier and better than the standard surface ECG. Continuous preventive ischemia monitoring using the implanted ICD thus appears possible in patients at risk of infarction.     

Cardiopulmonary resuscitation in a rat model of chronic myocardial ischemia.

Our group has developed a rat model of cardiac arrest and cardiopulmonary resuscitation (CPR). However, the current rat model uses healthy adult animals. In an effort to more closely reproduce the event of cardiac arrest and CPR in humans with chronic coronary disease, a rat model of coronary artery constriction was investigated during cardiac arrest and CPR. Left coronary artery constriction was induced surgically in anesthetized, mechanically ventilated Sprague-Dawley rats. Echocardiography was used to measure global cardiac performance before surgery and 4 wk postsurgery. Coronary constriction provoked significant decreases in ejection fraction, increases in left ventricular end-diastolic volume, and increases left ventricular end-systolic volume at 4 wk postintervention, just before induction of ventricular fibrillation (VF). After 6 min of untreated VF, CPR was initiated on three groups: 1) coronary artery constriction group, 2) sham-operated group, and 3) control group (without preceding surgery). Defibrillation was attempted after 6 min of CPR. All the animals were resuscitated. Postresuscitation myocardial function as measured by rate of left ventricular pressure increase at 40 mmHg and the rate of left ventricular pressure decline was more significantly impaired and left ventricular end-diastolic pressure was greater in the coronary artery constriction group compared with the sham-operated group and the control group. There were no differences in the total shock energy required for successful resuscitation and duration of survival among the groups. In summary, this rat model of chronic myocardial ischemia was associated with ventricular remodeling and left ventricular myocardial dysfunction 4 wk postintervention and subsequently with severe postresuscitation myocardial dysfunction. This model would suggest further clinically relevant investigation on cardiac arrest and CPR.     

Resveratrol ameliorates myocardial damage by inducing vascular endothelial growth factor-angiogenesis and tyrosine kinase receptor Flk-1

In our study, resveratrol (polyphenol) has been identified as a very important stimulus/agent for the induction of new vessel growth. Occlusion of a main coronary depletes the blood supply to the myocardium and subsequently reduces cardiac function, which ultimately leads to heart failure. Progressive, chronic coronary artery occlusion has been shown to induce development of collateral arteries to re-establish and maintain blood flow to the myocardium at risk via the growth of new capillary vessels or angiogenesis. Studies from our laboratory, as well as from others, have already confirmed the protective role of collaterals against myocardial ischemia and cell death. We have successfully demonstrated in rat myocardial infarction (MI) model an effect of resveratrol on significant upregulation of the protein expression profiles of vascular endothelial growth factor (VEGF) and its tyrosine kinase receptor Flk-1, 3 wk after MI. Pretreatment with resveratrol also increased nitric-oxide synthase (inducible NOS and endothelial NOS) along with increased antiapoptotic and proangiogenic factors nuclear factor (NF)-kappaB and specificity protein (SP)-1. We also were able to demonstrate increased capillary density as well as improved left ventricular function by pharmacological preconditioning with resveratrol 3 wk after MI.     

Increased susceptibility to ventricular arrhythmias in a rodent model of experimental depression

Depression is an important public health problem and is considered to be an independent risk factor for coronary artery disease. The pathophysiological mechanisms that link depression with adverse cardiovascular events (e.g., myocardial ischemia, myocardial infarction, and sudden death) are not well established. It is possible that an increased susceptibility to life-threatening cardiac arrhythmias in depressed patients influences the risk of morbidity and mortality in coronary artery disease. This idea was tested with the use of an experimental model of depression that was developed to induce anhedonia, the reduced responsiveness to pleasurable stimuli observed in human depressed patients. Rats exposed to 4 wk of chronic mild stress (e.g., paired housing, strobe light, and white noise) displayed anhedonia, which was operationally defined by the reduced intake of a palatable sucrose solution relative to an established baseline and to control animals. Furthermore, compared with control rats, the anhedonic rats showed increased basal heart rate and decreased heart rate variability. In response to an intravenously infused chemical challenge, aconitine, anhedonic rats exhibited an increased vulnerability to ventricular arrhythmias, as indicated by a reduced threshold for premature ventricular complexes, salvos, and ventricular tachycardia. These findings suggest that the presence of depressive symptoms is associated with a lower threshold for ventricular arrhythmias, which may contribute to the increased risk for adverse cardiovascular events in patients with depression.     

Myocardial infarction and heart failure in the db/db diabetic mouse

Clinical studies have reported that the incidence and severity of myocardial infarction is significantly greater in diabetics compared with nondiabetics after correction for all other risk factors. The majority of studies investigating the pathophysiology of myocardial ischemia-reperfusion injury have focused on otherwise healthy animals. At present, there is a paucity of experimental investigations on the pathophysiology of heart failure in diabetic animals. We hypothesized that the severity of myocardial reperfusion injury and the development of congestive heart failure would be markedly enhanced in the db/db diabetic mouse. Accordingly, we studied the effects of varying durations of in vivo myocardial ischemia and reperfusion on the incidence of heart failure in db/db diabetic mice. Nondiabetic and db/db diabetic mice (10 wk of age) were subjected to 30, 45, or 60 min of left coronary artery occlusion and 28 days of reperfusion. Survival at 24 h of reperfusion was 100% in nondiabetic mice subjected to 30 min of myocardial ischemia and 88% in nondiabetic mice subjected to 45 min of myocardial ischemia. In contrast, survival was 53% in db/db diabetic mice subjected to 30 min of myocardial ischemia and 44% in db/db mice after 45 min of myocardial ischemia. Prolonged survival in nondiabetic mice was not significantly attenuated when compared during the 28-day follow-up period with all groups experiencing >90% survival. Prolonged survival was significantly decreased in db/db mice after both 30 and 45 min of myocardial ischemia compared with sham controls. Furthermore, we observed a significant degree or left ventricular dilatation, cardiac hypertrophy, and cardiac contractile dysfunction in db/db mice subjected to 45 min of myocardial ischemia and 28 days reperfusion. In nondiabetic mice subjected to 45 min of myocardial ischemia, we failed to observe any changes in left ventricular dimensions or fractional shortening. These studies provide a feasible experimental model system for the investigation of heart failure secondary to acute myocardial infarction in the db/db diabetic mouse.     

Implantable cardioverter defibrillator: an update

Automatic implantable cardioverter defibrillator is now a well established therapy to prevent sudden cardiac death. In secondary prevention (patients with a previous cardiac arrest) defibrillator can be considered as a class I indication, if there is no transient or reversible cause. The level of proof is A. in primary prevention the defibrillator is indicated in coronary artery disease patients with or without symptoms of mild to moderate heart failure (NYHA II or III), an ejection fraction lower than 30 %, measured at least one month after a myocardial infarction and 3 months after a revascularisation, surgery or angioplasty (level of proof B). It is also indicated in symptomatic spontaneous sustained ventricular tachycardias with underlying heart disease (level of proof B), in patients with spontaneous sustained ventricular tachycardia, poorly tolerated, without underlying heart disease for which pharmacological treatment or ablation can not be performed or failed (level of proof B). Finally it is also indicated in patients with syncope of unknown cause with sustained ventricular tachycardia or inducible ventricular fibrillation, with an underlying heart disease (level of proof B). The guidelines proposed by the different societies have also proposed class IIa recommendations which are the following: coronary artery disease patients with left ventricular dysfunction (ejection fraction between 31 or 35 %) measured at least one month after a myocardial infarction and 3 months after a revascularisation with an inducible ventricular arrhythmia. It can be also indicated in idiopathic dilated cardiomyopathies with an ejection fraction lower than 30% and NYHA class II or III. It can be also indicated in familial or inherited conditions with a high risk of sudden cardiac death by ventricular fibrillation without any other efficient known treatment and finally in heart failure patients remaining symptomatic, in class III or IV NYHA, with an optimal medical therapy, an ejection fraction lower than 35 % and a QRS complex duration higher than 120 ms: in this case it is an indication of cardiac resynchronization therapy device associated to the defibrillator. All these class IIa indications have a level of proof B.     

扶正化瘀胶囊对心肌梗死大鼠心肌纤维化的影响

目的：急性心肌梗死是危害人类健康的重大疾病之一,心肌梗死后心肌纤维化是造成心脏结构破坏、心功能下降、心律失常发生、心衰甚至猝死的微观病理机制。防治心肌纤维化是当前医学研究的重点和热点。本研究主要探讨扶正化瘀胶囊对心肌梗死大鼠心肌纤维化的干预作用。方法：大鼠随机分为假手术组、模型组、扶正化瘀胶囊组和卡托普利组,采用结扎冠状动脉前降支的方法建立心肌梗死模型,假手术组只穿线,不结扎。于造模成功后第10天开始给予相应药物治疗2个月。治疗结束后,检测左心室梗死范围和心肌胶原含量。结果：与假手术组比较,模型组、扶正化瘀胶囊组和卡托普利组的非梗死区面积显著减小（P〈0.01）。与模型组比较,扶正化瘀胶囊组和卡托普利组的梗死区面积和梗死百分比显著减小（P〈0.05,P〈0.01）。在心肌胶原表达上,与假手术组比较,模型组和扶正化瘀胶囊组胶原含量显著增加（P〈0.01）。与模型组比较,卡托普利组和扶正化瘀胶囊组胶原含量显著降低（P〈0.05,P〈0.01）。结论：扶正化瘀胶囊能够改善心肌缺血,缩小心肌梗死范围,抑制心肌胶原表达,除能用于肝纤维化的治疗外,还能用于防治心肌梗死后的心肌纤维化。     

Recommendations from the Consensus Conference on Hypertension in the Elderly.

Since 1978 there have been dramatic advances in the understanding of the pathophysiologic features of unstable angina pectoris and in the availability of new therapies of proven efficacy. Coronary artery spasm has been shown to be an important mechanism of acute myocardial ischemia in patients with unstable angina, and coronary thrombosis has been established as an early event in the development of acute myocardial infarction and, possibly, sudden death. Intravenous nitrates and oral calcium antagonists have been made available and are now widely used. Acetylsalicylic acid has been shown to be of benefit. Improved techniques of myocardial preservation and the introduction of percutaneous transluminal coronary angioplasty have modified the surgical management of coronary artery disease.     

Stent implantation at the site of the myocardial bridge after myocardial infarction. Long-term results

Although myocardial bridge is asymptomatic in most patients, it can lead to myocardial ischemia, myocardial infarction, cardiac arrhythmias, and sudden death. The authors report the case of a symptomatic myocardial bridge treated by classical stenting of the mid left anterior descending artery. The outcome was good. A control coronary angiography performed 36 months later showed no significant restenosis. No recurrence of angina during five years follow-up was observed.     

Intrinsic defensive mechanisms in the heart: a potential novel approach to cardiac protection against ischemic injury

Despite recent advances in pharmacotherapy of coronary artery disease and interventional cardiology, the management of myocardial ischemia still remains a major challenge for basic scientists and clinical cardiologists. An urgent need to combat ischemic heart disease, its forms, such as infarction, and complications including sudden cardiac death led to the development of an alternative strategy of myocardial protection based on the exploitation of the heart's own intrinsic protective mechanisms. A new concept relies on the evidence that the heart is able to protect itself by way of adaptation, either short-term or long-term, to transient episodes of stress (e.g., ischemia, hypoxia, free oxygen radicals, heat stress, etc.) preceding sustained ischemia. Preconditioning by brief episodes of ischemia (ischemic preconditioning, IP) represents the most powerful cardioprotective phenomenon. Apart from the short-lasting protection afforded by classical IP or its delayed ("second window") phase, adaptation to long-lasting physiological stimuli or pathological processes is also known to increase myocardial resistance to ischemic injury. Although molecular mechanisms of cardiac adaptation conferring a higher ischemic tolerance still remain not sufficiently elucidated, multiple cascades of intracellular signalization are suggested to be involved in this process. Experimental studies led to the observations that pharmacological modulations at different levels of signal transduction might mimic protective effects of the adaptive phenomena and thus provide a safer way of inducing cardioprotection in humans.     

Commotio cordis

Sudden arrhythmic death as a result of a blunt chest wall blow has been termed Commotio Cordis (CC). CC is being reported with increasing frequency with more than 180 cases now described in the United States Commotio Cordis Registry. The clinical spectrum is diverse; however young athletes tend to be most at risk, with victims commonly being struck by projectiles regarded as standard implements of the sport. Sudden death is instantaneous and victims are most often found in ventricular fibrillation (VF). Chest blows are not of sufficient magnitude to cause any significant damage to overlying thoracic structures and autopsy is notable for the absence of any structural cardiac injury. Development of an experimental model has allowed for substantial insights into the underlying mechanisms of sudden death. In anesthetized juvenile swine, induction of VF is instantaneous following chest impacts that occur during a vulnerable window before the T wave peak. Other critical variables, including the impact velocity and location, and the hardness of the impact object have also been identified. Rapid left ventricular pressure rise following chest impact likely results in activation of ion channels via mechano-electric coupling. The generation of inward current through mechano-sensitive ion channels results in augmentation of repolarization and non-uniform myocardial activation, and is the cause of premature ventricular depolarizations that are triggers of VF in CC. Currently available chest protectors commonly used in sport are not adequately designed to prevent CC. The development of more effective chest protectors and the widespread availability of automated external defibrillators at youth sporting events could improve the safety of young athletes.     

Circadian Variation of Myocardial Ischemia in Patients with Stable Coronary Artery Disease

The circadian variation of myocardial ischemia detected during 24-h ambulatory electrocardiographic monitoring (AEM) was analyzed in 123 patients with stable angina pectoris, positive exercise test, and angiographically proven coronary artery disease. A total of 437 ischemic episodes (ST-segment depression ≥ 1 mm and duration ≥ 1 min) were observed; 333 (76%) episodes remained asymptomatic, and only 104 (24%) episodes were accompanied by anginal pain. Ischemic episodes predominantly occurred during the morning hours, between 6 a.m. and noon, and another smaller peak was observed in the afternoon, between 4 and 5 p.m.; this diurnal pattern was influenced neither by the extent of coronary artery disease nor the degree of left ventricular dysfunction. The circadian variation was restricted to the 345 (78%) ischemic episodes preceded by increases in heart rate; the 92 (22%) episodes without prior heart rate changes occurred randomly throughout the day. The morning peak in ischemic episodes was not associated with less myocardial oxygen supply; in contrast, heart rate profile showed parallel increases during the morning and afternoon hours, indicating elevated myocardial demand during these periods. Ischemia-related ventricular arrhythmias were concentrated during the morning hours, but their overall prevalence was low-28 (6%) of 437 ischemic episodes. These findings may provide further insight into the pathomechanisms of acute clinical events in patients with coronary artery disease, since the circadian variation of myocardial ischemia is very similar to that observed for the onset of myocardial infarction and sudden cardiac death.     

Effect of myocardial infarction and ischemia on induction of cardiac reentries and ventricular fibrillation

The present work is aimed at investigating the effects of myocardial infarction and ischemia on induction of ventricular fibrillation. Electrophysiologic effects of global and local ischemia (variation of the dispersion of refractory periods as well as conduction velocity) on initiation of reentry mechanisms was studied by means of computer simulations based on a cellular automata model of propagation of activation wave through a ventricular surface element. A local area of ischemia where effects of the dispersion of refractory periods are investigated is then simulated. This is made using a Gaussian distribution characterized by its mean and standard deviation. These simulations show that ischemia is capable of initiating reentry phenomena which propagate through the whole ventricle; they are responsible for ventricular fibrillation which causes sudden cardiac death, even when ischemia only involves limited parts of the myocardium. Statistical study of the probability of reentries as a function of both of the size of ischemic zones and the rate of dispersion of refractory periods shows that the latter parameter is of primary importance in triggering cardiac reentries.     

Circadian Variation of Myocardial Ischemia in Patients with Stable Coronary Artery Disease

The circadian variation of myocardial ischemia detected during 24-h ambulatory electrocardiographic monitoring (AEM) was analyzed in 123 patients with stable angina pectoris, positive exercise test, and angiographically proven coronary artery disease. A total of 437 ischemic episodes (ST-segment depression ≥ 1 mm and duration ≥ 1 min) were observed; 333 (76%) episodes remained asymptomatic, and only 104 (24%) episodes were accompanied by anginal pain. Ischemic episodes predominantly occurred during the morning hours, between 6 a.m. and noon, and another smaller peak was observed in the afternoon, between 4 and 5 p.m.; this diurnal pattern was influenced neither by the extent of coronary artery disease nor the degree of left ventricular dysfunction. The circadian variation was restricted to the 345 (78%) ischemic episodes preceded by increases in heart rate; the 92 (22%) episodes without prior heart rate changes occurred randomly throughout the day. The morning peak in ischemic episodes was not associated with less myocardial oxygen supply; in contrast, heart rate profile showed parallel increases during the morning and afternoon hours, indicating elevated myocardial demand during these periods. Ischemia-related ventricular arrhythmias were concentrated during the morning hours, but their overall prevalence was low–28 (6%) of 437 ischemic episodes. These findings may provide further insight into the pathomechanisms of acute clinical events in patients with coronary artery disease, since the circadian variation of myocardial ischemia is very similar to that observed for the onset of myocardial infarction and sudden cardiac death.     

A role for decorin in the remodeling of myocardial infarction.

Because the small leucine-rich proteoglycan decorin has been implicated in regulation of collagen fibrillogenesis leading to proper extracellular matrix assembly, we hypothesized it could play a key role in cardiac fibrosis following myocardial infarction. In this study we ligated the left anterior descending coronary artery in wildtype and decorin-null mice to produce large infarcts in the anterior wall of the left ventricle. At early stages post-coronary occlusion the myocardial infarction size did not appreciably differ between the two genotypes. However, we found a wider distribution of collagen fibril sizes with less organization and loose packing in mature scar from decorin-null mice. Thus, we tested the hypothesis that these abnormal collagen fibrils would adversely affect post-infarction mechanics and ventricular remodeling. Indeed, scar size, right ventricular remote hypertrophy, and left ventricular dilatation were greater in decorin-null animals compared with wildtype littermates 14 days after acute myocardial infarction. Echocardiography revealed depressed left ventricular systolic function between 4 and 8 weeks post-ischemia in the decorin-null animals. These changes indicate that decorin is required for the proper fibrotic evolution of myocardial infarctions, and that its absence leads to abnormal scar tissue formation. This might contribute to aneurysmal ventricular dilatation, remote hypertrophy, and depressed ventricular function.     

Electrotonic remodeling following myocardial infarction in dogs susceptible and resistant to sudden cardiac death.

Passive electrical remodeling following myocardial infarction (MI) is well established. These changes can alter electrotonic loading and trigger the remodeling of repolarization currents, a potential mechanism for ventricular fibrillation (VF). However, little is known about the role of passive electrical markers as tools to identify VF susceptibility post-MI. This study investigated electrotonic remodeling in the post-MI ventricle, as measured by myocardial electrical impedance (MEI), in animals prone to and resistant to VF. MI was induced in dogs by a two-stage left anterior descending (LAD) coronary artery ligation. Before infarction, MEI electrodes were placed in remote (left circumflex, LCX) and infarcted (LAD) myocardium. MEI was measured in awake animals 1, 2, 7, and 21 days post-MI. Subsequently, VF susceptibility was tested by a 2-min LCX occlusion during exercise; 12 animals developed VF (susceptible, S) and 12 did not (resistant, R). The healing infarct had lower MEI than the normal myocardium. This difference was stable by day 2 post-MI (287 +/- 32 Omega vs. 425 +/- 62 Omega, P < 0.05). Significant differences were observed between resistant and susceptible animals 7 days post-MI; susceptible dogs had a wider electrotonic gradient between remote and infarcted myocardium (R: 89 +/- 60 Omega vs. S: 180 +/- 37 Omega). This difference increased over time in susceptible animals (252 +/- 53 Omega at 21 days) due to post-MI impedance changes on the remote myocardium. These data suggest that early electrotonic changes post-MI could be used to assess later arrhythmia susceptibility. In addition, passive-electrical changes could be a mechanism driving active-electrical remodeling post-MI, thereby facilitating the induction of arrhythmias.