Method for evaluating the effects of antiarrhythmic drugs on ventricular tachycardias with different electrophysiologic characteristics and different mechanisms in the infarcted canine heart

In a canine model of myocardial infarction caused by coronary occlusion and reperfusion, ventricular tachycardia occurs spontaneously at 24 hours and has many of the characteristics of an accelerated idioventricular rhythm. It cannot be induced by premature or rapid stimulation of the ventricles; overdrive pacing during this tachycardia usually causes some transient overdrive suppression but occasionally there is overdrive acceleration. We suggest that this arrhythmia is caused mainly by enhanced automaticity. Ventricular tachycardia also can be induced by premature or rapid ventricular pacing 3 to 5 days after infarction, but it does not occur spontaneously. It can be stopped by overdrive pacing, suggesting that it is caused by reentry. Electrocardiographic features are identical to chronic, recurrent sustained ventricular tachycardia in human patients. Because the arrhythmias occurring at different times probably result from different mechanisms this canine model is useful for comparing the actions of drugs on different kinds of arrhythmias. Lidocaine and procainamide generally abolished tachycardia 24 hours after infarction, but only procainamide abolished tachycardia 3 to 5 days after infarction. Isoproterenol accelerated tachycardia at both times. Verapamil did not abolish tachycardia 3 to 5 days after infarction.     

Inducible sustained ventricular tachycardia and ventricular fibrillation in conscious dogs with isolated right ventricular infarction: relation to infarct structure

The susceptibility of infarcted right ventricular myocardium to inducible ventricular tachyarrhythmias was serially evaluated in 18 conscious dogs during the first 2 weeks after permanent right coronary artery occlusion. Properly timed double premature stimuli applied to the right ventricular outflow tract induced sustained (longer than 1 minute) ventricular tachycardia at rates of 190 to 400 beats/min in nine dogs, and ventricular fibrillation in six dogs. No ventricular arrhythmias could be induced in the remaining three dogs. The zone of premature coupling intervals within which ventricular tachyarrhythmias could be induced decreased in each dog as the infarct aged, and by day 12 after occlusion, no ventricular arrhythmias could be induced in any of the dogs studied. Both the size and the degree of patchiness (graded from 0 for no patchiness to +4 for patchiness throughout the infarct) of the infarct appear to be related to the nature of the induced rhythm. Infarcts with greater heterogeneity and those that were larger than 8% of the right ventricular volume were associated with a higher incidence of ventricular fibrillation, and infarcts with a lesser degree of patchiness were more suitable for sustained ventricular tachycardia (3.4 +/- 1.2 versus 1.4 +/- 0.4, p less than 0.05). These findings indicate that the infarcted right ventricular myocardium, independent of left ventricular involvement, can be associated with malignant ventricular tachyarrhythmias, ventricular tachyarrhythmias can be induced only during a well defined postinfarction period; and both the size and geometry of the right ventricular infarct determine the nature of the induced ventricular rhythm.     

Serial analysis of spontaneous and induced ventricular arrhythmias in a canine model of myocardial infarction

To study the time course of spontaneous and induced ventricular arrhythmias after myocardial infarction (MI), 20 dogs underwent ligation of the left anterior descending coronary artery and temporary occlusion and reperfusion of the obtuse marginal branch. There were 5 early deaths (less than 24 hours) due to spontaneous ventricular fibrillation (VF). All 15 survivors exhibited spontaneous ventricular tachycardia (VT) up to day 3 with the shortest cycle length occurring at 17 hours after MI (232 +/- 11 msec: mean +/- SEM). The grade of arrhythmia complexity was decreased after day 4 compared to day 1 (p = 0.049), and the number of ventricular premature complexes was reduced after day 6 (1700 +/- 1390/hour) compared to day 1 (9500 +/- 640/hour, p = 0.042). Serial electrophysiologic studies were carried out on days 8, 15, 22, and 29 via an implanted antitachycardia pacemaker using 1 to 3 extrastimuli and rapid ventricular pacing (RVP). On day 8, VT was inducible in 7 dogs (46%), VF in 4 (27%), and 4 dogs (27%) exhibited a negative response. On day 15, 3 more dogs became negative, and all previously negative dogs displayed negative responses. From day 15, the inducibility of VT/VF remained "constant" using RVP. However, inducibility by triple extrastimuli declined week by week until day 29. Stepwise logistic regression analysis of 20 variables selected the mass of the MI as the only independent predictor of inducible VT/VF by multiple extrastimuli and RVP after day 15 (p = 0.049). Thus significant time- and mode-dependent changes in inducibility of VT/VF occur during the early phase after MI.     

Divergent time courses of ventricular vulnerability of the heart to ventricular tachycardias and ventricular fibrillation in the early necrosis stage of acute experimental myocardial infarct

Early necrosis in acute experimental myocardial infarction is characterized by severe ventricular dysrhythmias beginning approx. 6 hours after coronary artery occlusion and persisting for 2-5 days. It was the aim of this study to investigate the comparative changes in ventricular vulnerability to spontaneous and stimulus-induced tachycardia and fibrillation during early necrosis 6-18 hours following acute coronary artery occlusion. Results: 1) The thresholds for repetitive extrasystoles and for ventricular fibrillation determined via electrodes placed on to the endocardium of the right and left ventricle outside of the ischemic area are within the normal range of the non-ischemic heart. 2) Both stimulation thresholds increase significantly within the area of infarction and in many cases are not inducible any more after 18 hours of ischemia, whatever amount of current is applied. 3) Sustained ventricular tachycardia can be induced in about 30% of cases after an occlusion lasting approx. 6 hours and in about 80% after an occlusion period of 18 hours. 4) Electrically induced ventricular tachycardias differ from spontaneously occurring VT in so far as the former appear to be due to a reentry mechanism, whereas the latter seem to be "accelerated ventricular rhythms" and thus of focal origin. Our results demonstrate that enhanced ventricular vulnerability during early necrosis in acute myocardial infarction is predominantly due to ventricular tachycardia rather than to ventricular fibrillation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of verapamil on ventricular rhythm during acute coronary occlusion

The effects of verapamil on electrophysiologic parameters of the ventricle were studied during acute coronary occlusion in anesthetized open-chest dogs. Those parameters measured in the study were idioventricular automaticity, ventricular conduction, and fibrillation threshold. The incidence of rapidly repetitive beats and fibrillation induced by two successive premature beats was also studied. Verapamil significantly decreased idioventricular automaticity (in five dogs), improved conduction through the ischemic area (in six dogs), and increased fibrillation threshold of the ischemic ventricular (in eight dogs). The drug was effective in abolishing rapidly repetitive beats and fibrillation induced by closely coupled premature beats during acute coronary occlusion. Rapidly repetitive beats occurred in nine out of 15 dogs and these repetitive beats were degenerated into fibrillation in seven dogs before verapamil. Following pretreatment with the drug, rapidly repetitive beats and fibrillation occurred in none of the 15 dogs. The results indicate that verapamil can be very effective against ventricular arrhythmias occurring in association with myocardial infarction.     

Precordial mechanical stimulation for exposing electrical instability in the ischemic heart.

Sequenital mechanical pulsing of the chest wall with three stimuli failed to induce arrhythmias in normal dogs. After coronary arterial occlusion, this technique evoked in 11 of 12 animals repetitive ventricular tachycardia in 2. These responses corresponded closely to those elicited by electrical testing. In four conscious animals after recovery from myocardial infarction, precordial pulsing induced repetitive ventricular arrhythmias. The type of arrhythmia produced depended on the degree of prematurity of the third pulse in the sequence. The use of precordial mechanical stimulation can perhaps be modified and adapted as a method of detecting persons at high risk for sudden cardiac death.     

Electrophysiologic mapping to determine the mechanism of experimental ventricular tachycardia initiated by premature impulses: Experimental approach and initial results demonstrating reentrant excitation

Epicardial activation patterns were determined during repetitive responses and nonsustained and sustained ventricular tachycardias induced by premature impulses in infarcted canine hearts. A multiplexing system enabled recordings to be obtained from up to 192 electrodes simultaneously either from the entire epicardial surface with a sock electrode array or only from the sheet of epicardial muscle that survives over the infarcts, with a plaque electrode array. In hearts with an infarct caused by permanent occlusion of the left anterior descending coronary artery, the earliest epicardial excitation during nonsustained tachycardias occurred on the anterior left ventricle at the border of the infarcted region and in epicardial muscle surviving over the infarcted region. Circuituous conduction patterns leading to reentry occurred in the epicardial muscle over the infarct and probably caused the arrhythmias. During sustained tachycardia in hearts with an infarct caused either by permanent or temporary occlusion of the left anterior descending coronary artery, the earliest epicardial excitation also occurred at the border of the infarcted region, but there was no evidence of reentry in the surviving epicardial muscle.     

Transient ischaemia induced by rapid cardiac pacing results in myocardial preconditioning.

STUDY OBJECTIVE--The aim was to determine whether rapid ventricular pacing can protect against the ventricular arrhythmias occurring during a subsequent coronary artery occlusion. DESIGN--The effect was examined of two 2 min periods of pacing (300 beats.min-1) in chloralose-urethane anaesthetised dogs on a subsequent 25 min coronary artery occlusion. Ventricular arrhythmias, ST segment elevation, and inhomogeneity of conduction were analysed. EXPERIMENTAL MATERIAL--25 anaesthetised mongrel dogs in a restricted body weight range were used. MEASUREMENTS AND MAIN RESULTS--Preocclusion pacing reduced the severity of occlusion induced ST segment elevation, degree of inhomogeneity, and arrhythmias: ventricular premature beats were reduced from 528(SEM 40) to 136(45), and there were lower incidences of ventricular fibrillation (0% v 47%) and ventricular tachycardia (30% v 80%). CONCLUSIONS--Rapid ventricular pacing "preconditions" the myocardium in a manner similar to that following short coronary artery occlusions. Short periods of ischaemia no matter how induced protect the heart against the arrhythmogenic effect of a prolonged coronary artery occlusion.     

Flunarizine allows differentiation between mechanisms of arrhythmias in the intact heart

The calcium antagonist flunarizine suppresses pathologic accumulation of calcium intracellularly without affecting the fast sodium or the slow calcium channel. To establish its value in differentiating between mechanisms of arrhythmias in the canine heart, the effect of flunarizine was investigated on ventricular tachycardia (VT) induced by ouabain intoxication or occurring 16-24 hours after occlusion of the left anterior descending coronary artery. Four groups of dogs were studied. Group 1 consisted of 13 animals with VT induced by ouabain intoxication (triggered-activity group). Group 2 included nine dogs in whom VT developed 16-24 hours after occlusion of the left anterior descending coronary artery (abnormal automaticity group). Group 3 included six dogs with normally conducted sinus beats, whereas group 4 consisted of six animals having a ventricular escape rhythm. With the exception of group 3, all dogs had surgically induced complete atrioventricular block. All animals were studied while conscious and without premedication. In groups 1 and 2, 2-3 mg/kg flunarizine was given intravenously after VT had persisted for at least 20 minutes. In groups 3 and 4, 2 mg/kg flunarizine was given after the rhythm was registered for 20 minutes. The cycle lengths of the different rhythms were compared before and after flunarizine. In group 1, flunarizine increased the cycle length of the VT from 300 +/- 30 to 410 +/- 50 msec (p less than or equal to 0.001). Termination of VT was seen in 11 out of 13 animals. In group 2, flunarizine resulted in a nonsignificant shortening of the RR interval from 450 +/- 60 to 440 +/- 60 msec. Persistent termination was observed in only one of nine dogs.(ABSTRACT TRUNCATED AT 250 WORDS)     

Prediction of sudden death by electrophysiologic studies in high risk patients surviving acute myocardial infarction

Seventy patients surviving a myocardial infarction complicated by heart failure or arrhythmias, or both, were studied 7 to 20 days after the infarction. Twenty-four hour electrocardiographic ambulatory monitoring and intracardiac electrophysiologic studies were performed in each patient. Electrophysiologic studies included introduction of single right ventricular premature stimuli during sinus rhythm (70 patients), atrial pacing (35 patients) and ventricular pacing (70 patients) at a stimulating voltage of 2 V, with the use of higher stimulating voltages (up to 10 V), and double right ventricular premature stimuli in 33 patients and pacing at a second right ventricular site in 50 patients. A repetitive response was defined as two or more spontaneous ventricular depolarizations in response to the premature stimuli, with His bundle reentry and aberrant conduction of supraventricular impulses excluded by a His bundle recording. Repetitive responses were initiated in 20 patients, and 12 patients had responses that were either sustained ventricular tachycardia or self-terminating ventricular tachycardia of more than five complexes in duration. The finding of a repetitive response was not related to the occurrence of complex ventricular arrhythmias during ambulatory monitoring or in the coronary care unit.Five of the 12 patients with sustained or self-terminating responses of more than five complexes died during the 12 month follow-up period, 4 suddenly, and these responses were significantly associated with late sudden death (p < 0.05), because only 1 of 25 patients with responses of fewer than five complexes or no response to maximal provocation died suddenly. It is concluded that induced responses of more than five complexes in duration may be an important indicator of a potentially reversible risk of sudden death after myocardial infarction.     

Experimental coronary artery ligation in conscious dogs six months after bilateral cardiac sympathectomy

The effects of left circumflex coronary artery (LCA) occlusion six months after bilateral cardiac sympathectomy on mortality, arrhythmias, and myocardial norepinephrine were studied with functional and histologic assessment of sympathetic regeneration. Bilateral stellate ganglionectomy, thoracic sympathectomy, and ansectomy (BSTG) were performed on 23 dogs and denervation was confirmed by electrical stimulation. Six months later, the LCA was ligated by a two-stage technique in these dogs (BSTG-6 mo.) and 23 control dogs in the conscious state. All dogs were autopsied at death or after 48 hours. Mortality at 15 minutes from ventricular fibrillation (VF) was 22 per cent in BSTG-6 mo. dogs and 52 per cent in control animals (p < 0.05). Mortality in the two groups at 24 hours was 44 per cent and 65 per cent, respectively. Before LCA occlusion, sinus arrhythmia was present in 23 per cent of the BSTG-6 mo. dogs and 82 per cent of the control animals. A significantly greater percentage increase in the sinus cardiac rate one minute after LCA occlusion was present in control dogs compared to BSTG-6 mo. dogs (p < 0.005). There was a later onset of ventricular arrhythmias, lesser incidence of ventricular premature beats (VPB) and ventricular tachycardia (VT), and a shorter duration of VT in BSTG-6 mo. dogs than in control animals. Myocardial norepinephrine levels were similar in BSTG-6 mo. and control dogs and fell after coronary occlusion by a comparable degree in the healthy and infarcted ventricles in both groups. Upper thoracic spinal cord stimulation (SCS) produced a mean 10 per cent increase in heart rate of three dogs four weeks after BSTG; and a 21 per cent increase in five BSTG-6 mo. animals in contrast with a 78 per cent increase in five control animals. Only one BSTG-6 mo. dog showed an almost normal (68 per cent) response to SCS. Histologic studies showed neural regeneration on the right side in one out of four BSTG-6 mo. dogs. Thus after six months, BSTG still confered a protective effect from VF following experimental coronary occlusion in conscious dogs, especially in the early, most critical period following myocardial infarction. Functional and histologic studies demonstrated sympathetic re-innervation in 20 to 25 per cent of the BSTG-6 mo. dogs.     

The duration of coronary occlusion influences adrenergic contributions to reperfusion ventricular arrhythmias

Summary To study the role of the adrenergic nervous system in the genesis of nonlethal reperfusion arrhythmias, the proximal left anterior descending coronary artery was occluded for either 1 or 3 hours in 48 open-chest dogs anesthetized with alpha-chloralose. Heart rate was controlled (90 to 110 beats/min) by bilateral vagotomy and continuous right vagal stimulation. Dogs were treated with either saline, timolol (0.1 mg/kg), or prazosin (0.5 mg/kg) 15 minutes prior to reperfusion. Reperfusion after 1 hour of occlusion in saline-treated dogs evoked sustained polymorphic ventricular tachycardia (204±9 beats/min) that reverted to sinus rhythm by 15 minutes of reperfusion. The maximum rate of ventricular tachycardia was significantly reduced by both prazosin and timolol. Both drugs also caused about a 50% reduction in the total number of ectopic beats in the first 10 minutes of reperfusion. With a 3-hour occlusion, reperfusion in saline-treated dogs caused sustained polymorphic ventricular tachycardia (135±15 beats/min) which persisted for several hours. Neither timolol nor prazosin significantly altered the ventricular ectopic rate in these dogs. Furthermore, bilateral stellate transection, left stellate stimulation, isoproterenol (0.5 mg/kg), or methoxamine (100 ug/kg) all failed to alter the ventricular ectopic rate in the saline-treated dogs. Ventricular ectopy induced by reperfusion after a 1- or 3-hour occlusion was overdriven in all dogs by rapid atrial pacing. The results suggest that the nature of reperfusion-induced ventricular ectopy is highly dependent upon the preceeding duration of coronary occlusion. Whereas both alpha-1- and beta-adrenergic receptors appear to play an important role in the genesis of reperfusion-induced ectopy after a 1-hour occlusion, these receptors have little influence on reperfusion-induced ectopy after a 3-hour occlusion.     

Histopathologic correlates of inducible ventricular tachycardia in two experimental canine models of myocardial infarction

Ventricular tachyarrhythmias are the leading cause of sudden cardiac death. Determination of the substrates conducive to the initiation of ventricular tachyarrhythmias remains an important clinical goal. The purpose of this study was to correlate electrophysiologic and histopathologic parameters conducive to the initiation of sustained ventricular tachycardia using programmed electrical stimulation in two canine models of myocardial infarction. Histopathologic correlates included: infarct pattern (heterogeneous vs. homogeneous morphology), distribution (viable epicardial or endocardial rim), and size. Twenty-one adult dogs were randomly divided into two groups: (1) 12 dogs underwent two-stage, 2-hour occlusion of the proximal left anterior descending coronary artery (LAD); and (2) nine animals had permanent, complete occlusion of the LAD with latex embolization. Using programmed ventricular pacing with two premature ventricular extrastimuli, initiation of ventricular tachycardia was attempted at both 1 and 2 weeks after infarction with the chest closed and opened each time. Electrophysiologic evaluation of the infarct type correlated significantly with the histologic morphology of the infarction (p less than 0.001), the presence of a viable epicardial rim was an extremely important discriminating variable for ability to induce sustained ventricular tachycardia (p = 0.04). The presence of an endocardial rim was not significant (p = 1.0). Infarct size alone was only marginally related to ventricular tachycardia inducibility (p = 0.08). Non-uniform infarcts were more conducive to the initiation of sustained ventricular tachycardia than homogeneous infarcts (p = 0.025). The presence of a large, non-uniform infarct was the best overall discrimination variable for inducibility (p = 0.0002). Thus, in these experimental models, specific infarct morphologies correlate significantly with susceptibility to inducible sustained ventricular tachyarrhythmias.     

Anisotropic conduction and functional dissociation of ischemic tissue during reentrant ventricular tachycardia in canine myocardial infarction

We measured the conduction characteristics at the epicardial surface of the left anterior ventricular wall in the in situ canine heart before and 3 to 5 days (n = 9 dogs) after permanent occlusion of the left anterior descending coronary artery (LAD). During ventricular stimulation generating wavefronts conducted along the longitudinal or the transverse fiber direction, 61 unipolar electrograms were recorded with a fine-meshed plaque electrode. Before occlusion, the fastest conduction velocity was consistently found in a direction perpendicular to the nearby LAD segment (longitudinal direction), and the slowest velocity in a direction parallel to the LAD segment (transverse fiber direction). In 3- to 5-day-old infarct preparations, a layer of subepicardial muscle with 1 to 3 mm thickness survived over necrotic tissue. The velocities and directions of fast and of slow conduction measured in ischemic subepicardial muscle were not significantly different from preocclusion values during stimulation at a basic rate, but excitability was found to be depressed in response to premature stimuli. Premature impulses initiated in nonischemic myocardium and conducted into ischemic tissue in the longitudinal or in the transverse directions induced sustained (greater than 100 beats) monomorphic tachycardias during which figure-eight activation patterns were mapped with sock-array electrodes. During these tachycardias, the direction of the common reentrant wavefront of the figure-eight pattern was preferentially oriented along the longitudinal fiber direction, independently of the direction of the initiating impulse. When polymorphic beats were induced, tachycardia terminated spontaneously within 20 beats, or changed to a monomorphic pattern, as described above. In conclusion, the anisotropic organization of surviving subepicardial muscle overlying an infarct provides a spatial constraint that determines a preferential direction of reentrant propagation and may contribute to sustaining monomorphic tachycardia.     

Origin of so-called right and left ventricular arrhythmias in acute myocardial ischemia

The anatomic origin of ventricular arrhythmias occurring immediately after coronary arterial ligation was studied in 32 dogs. The electrocardiogram and seven single or composite bipolar electrograms were recorded from various sites within and surrounding the ischemic area in the left and right ventricles. Delay and fragmentation in the activation of the epicardial ischemic zone of the left ventricle, bridging diastole, preceded the appearance of ventricular arrhythmias and were continuous during the rhythm disorders. So-called left and right ventricular arrhythmias were associated with similar delay and fragmentation in left ventricular ischemic epicardial activity. Multiple and simultaneous activation of both the right and left ventricles produced ventricular fusion premature complexes. Multiple exit points increased before ventricular fibrillation occurred. The ultimate origin of premature ectopic impulse formation in the ventricles is not necessarily related to one or more exit points in either ventricle. Ischemic damage to the heart produces ventricular arrhythmias that appear to originate from both ventricles. The site of origin of ventricular arrhythmias should not be the sole factor in assessing the benign or malignant properties of the arrhythmia.     

The relationship between ventricular arrhythmias and ischemia-induced conduction delay in closed-chest animals within 24 hours of myocardial infarction

To investigate the myocardial conduction characteristics of premature impulses during the first 24 hours following coronary ligation and its relationship to late infarction ventricular arrhythmias, transmural electrodes were positioned in the normal and ischemic myocardium in nine dogs. Cardiac conduction in ischemic myocardium was delayed 15 minutes post coronary occlusion both in the epicardium and endocardium, both in the anterograde (base to apex) and retrograde (apex to base) direction, and was maintained at the same level throughout the experiment. Conduction across the border of ischemic myocardium from ischemic to the normal segment was also delayed, especially in the endocardium. Spontaneous ventricular arrhythmias recorded on Holter tapes showed significant increase in the number of premature ventricular complexes and ventricular tachyarrhythmias 9 hours after infarction. Thus our findings suggest that spontaneous arrhythmias occurring in the late phase of acute myocardial infarction (AMI) are independent of the ischemia-induced conduction delay and an alternate mechanism such as abnormal automaticity may be responsible for late ventricular arrhythmias.     

Morphologic correlates of technetium-99m stannous pyrophosphate imaging of acute myocardial infarcts in dogs.

To obtain insight into the mechanism(s) responsible for the direct visualization of acute myocardial infarcts by myocardial scintigraphy with technetium-99m stannous pyrophosphate (99mTc-PYP), scintigraphic and morphologic studies were performed in 22 dogs subjected to occlusion of the proximal left anterior descending coronary artery (LAD). Grossly visible myocardial infarcts occurred in ten of 11 dogs with LAD occlusion for one day, five with LAD occlusion for two days, two with LAD occlusion for seven days and two with LAD occlusion for 13 days. Rare, microscopic foci of necrosis were observed in one dog with LAD occlusion for one day, and no lesions were present in two dogs subjected to temporary LAD occlusion for eight minutes and reflow for 24 hours. In the latter three dogs, 99mTc-PYP myocardial scintigrams were negative. In the 19 dogs with gross infarcts, 99mTc-PYP myocardial scintigrams were strongly positive at one and two days after LAD occlusion, much less positive at seven days and faintly positive at 13 days after occlusion. Positive myocardial scintigrams in most showed "doughnut" patterns, with marked peripheral concentration of radioactivity around central zones of much lower activity. On histologic examination, the one and two-day-old infarcts exhibited subendocardially located central zones and surrounding peripheral zones, both of which showed distinctive histopathological and histochemical features, including the selective occurrence in the peripheral zones of calcified muscle cells with ultrastructurally demonstrable apatite-like crystals in mitochondria. Selective occurrence of high tissue levels of 99mTc-PYP radioactivity also was demonstrated in the peripheral zones of four infarcts. Hearts with older infarcts (seven and 13 days) showed progressive replacement of necrotic myocardium by granulation tissue and progressive reduction in calcium deposits in the areas of damage. The data obtained in this study establish a temporal and topographical relationship between calcium accumulation in acute myocardial infarcts and 99mTc-PYP uptake responsible for scintigraphic detection of the lesions with this radionuclide in dogs subjected to proximal LAD occlusion.     

Maximal revascularization (reperfusion) in intact conscious dogs after 2 to 5 hours of coronary occlusion.

Acute infarction was produced in intact conscious dogs by inflating a previously implanted balloon cuff around the left anterior descending coronary artery was occluded in 26 control dogs and reperfused by deflating the balloon cuff after 2 hours of occlusion in 19 dogs (group II) and after 5 hours in 11 dogs (group III). Serial studies were performed and repeated after 48 hours and 7 days. All three groups revealed hemodynamic and metabolic deterioration with coronary occlusion and infarct production. Immediately after reperfusion, arrhythmias developed in groups II and III and persistent ventricular tachycardia was present 2 to 3 hours after reperfusion in 74 percent of animals in group II and 82 percent of those in group III compared with 6 percent and 13 percent incidence rates at corresponding times in control dogs. Q waves developed in 83 percent of animals in group II and 100 percent of those in group III but in only 12 and 27 percent of control animals at corresponding times. Hemodynamic deterioration was accelerated in the postreperfusion period in both groups II and III. Angiographic assessment revealed improvement in 42 percent of dogs in group II, but in none of those in group III after reperfusion. Myocardial oxygen extraction diminished to subnormal levels after reperfusion, indicating either reactive hyperemia or shunting effect. Mortality was not significantly influenced by reperfusion. Infarct size was more than 15 percent of ventricular mass in 92 percent of control dogs and in 100 percent of dogs in group III, but in only 50 percent of those in group II. The data indicate that reperfusion in conscious dogs representing early, noninvasive maximal revascularization under ideal circumstances fails to prevent deterioration or death; instead it hastens the development of arrhythmias and myocardial injury. Reperfusion, although deleterious in the first hours, can reduce infarct size if performed after 2 hours, but not after 5 hours, of occlusion.     

Ventricular arrhythmias initiated by programmed stimulation in four groups of patients with healed myocardial infarction

Programmed electrical stimulation of the heart was prospectively used in 160 patients with healed myocardial infarction to study the incidence and characteristics of ventricular arrhythmias induced. Thirty-five patients had neither documented nor suspected ventricular arrhythmias (Group A); 37 patients had documented nonsustained ventricular tachycardia (Group B); 31 patients had been resuscitated from ventricular fibrillation (Group C); and 57 patients had documented sustained monomorphic ventricular tachycardia (Group D). No electrophysiologic differences were found between patients in Group A and Group B, but patients in both groups differed significantly from patients in Group C and Group D. In the last two groups, sustained monomorphic ventricular tachycardia was more frequently induced, the cycle length of the induced ventricular tachycardia was slower and a lesser number of premature stimuli was required for induction. No differences were found in the incidence, rate or mode of induction of nonsustained monomorphic ventricular tachycardia, but nonsustained polymorphic ventricular tachycardia and ventricular fibrillation were more frequently induced in Groups A and B. It is concluded that the substrate for sustained ventricular arrhythmia is present in at least 42% of patients after myocardial infarction. The electrophysiologic characteristics of the substrate for ventricular tachycardia seem to be the major determinant of the clinical occurrence of sustained ventricular arrhythmia. Changes in the electrophysiologic properties of the substrate of ventricular tachycardia, either spontaneously with time or induced by ischemia or antiarrhythmic drugs, can contribute to the clinical occurrence of sustained ventricular arrhythmias in patients with an old myocardial infarction.     

Enhanced induction of ventricular arrhythmias during sympathetic stimulation before and during coronary artery occlusion.

We used programmed electrical stimulation to examine the arrhythmogenic influence of the sympathetic nervous system before and during coronary artery occlusion. In 29 anesthetized dogs the left and/or right stellate ganglia were stimulated at 2-8 hertz. Program-induced ventricular arrhythmias included single premature ventricular depolarizations, doublets, triplets, ventricular tachycardia and ventricular fibrillation. Both the number of extrastimuli and the duration of coronary occlusion significantly influenced ventricular arrhythmia induction. After pooling the number of extrastimuli, type of artery occluded, and the duration of occlusion, the influences of unilateral and bilateral stellate stimulations were evaluated. The incidence of induced ventricular arrhythmias was 54% during control conditions (prior to sympathetic stimulation). Right stellate stimulation had no influence on arrhythmogenesis, causing ventricular arrhythmia induction in 52% (NS) of the trials. Left stellate stimulation resulted in increased ventricular arrhythmias (68%; P less than 0.05) in response to programmed electrical stimulation. Bilateral stellate stimulation elevated program-induced ventricular arrhythmias (63%; P less than 0.05). The effects of the stellate stimulations on arrhythmia induction were similar during and up to 180 minutes of coronary occlusion. Thus, the arrhythmogenic influence of sympathetic stimulation was present before and during coronary artery occlusion.