Ventricular arrhythmias, sudden death, and silent myocardial ischemia

Abstract

T HE ASSOCIATION between acute ischemia and ventricular arrhythmia in experimental animals is well established. Kaplinsky et al’ found two periods of early ventricular arrhythmia within 30 minutes of coronary occlusion in dogs. Janse et al* described two mechanisms of ventricular arrhythmia during acute experimental ischemia. At the normal side of the ischemic border they found a focal mechanism, induced possibly by injury currents in the normal Purkinje fibers, whereas in the ischemic myocardium they found macroand microreentry ventricular arrhythmia. Coronary occlusion in cats3 caused increased conduction time through the myocardium and epicardial regions, asynchronous depolarization and shortening of the refractory period, accompanied by ventricular arrhythmias. Kabell et al4 demonstrated that ischemia induced by reduction of collateral flow to an infarcted area in experimental animals, induced fractionation and delay of the electrogram in the infarcted zone and a higher frequency of pacing-induced ventricular tachycardia (VT). The effect of repeated 5-minute periods of ischemia followed by reperfusion on ventricular arrhythmia was assessed by Shiki and Hearse5 in rats; during reperfusion all animals exhibited VT and 83% of them exhibited ventricular fibrillation (VF). After conversion to sinus rhythm and following recovery, they were again subjected to 5-minute periods of ischemia and reperfusion. Following a short recovery period from the initial bout of ischemia only 8% to 17% of the experimental animals developed VT and none had VF, whereas longer recovery periods were associated with a progressive return of vulnerability. Thus, a very short period of ischemia and reperfusion “preconditioned” and protected the myocardium from reperfusion arrhythmias, but for only a short period of time. Recent evidence suggests that platelet activation may contribute to arrhythmogenesis during myocardial ischemia. Flores et al6 found that in ischemic myocardium platelets increased conduction time and reduced action potential duration. Further support for the role of platelets in inducing life-threatening arrhythmias was provided by Davies et al7 who described platelet aggregation as a frequent finding in patients with unstable angina suffering sudden ischemic cardiac death. The association between catecholamines, ischemia, and arrhythmia is a complex one. Within 10 minutes of ischemia the noradrenaline concentration in the myocardium is increased.8l” The accumulation of catecholamines in the extracellular space during ischemia in viable myocardium can cause malignant arrhythmia and acceleration of cell damage.‘O High doses of epinephrine decrease the resting membrane potential and action potential amplitude, slow conduction, and produce undirectional block; all these alterations predispose to reentrant arrhythmias. Epinephrine can also induce triggered activity, the underlying cause of automatic arrhythmias. i1,12 The importance of the sympathetic system during ischemia-induced arrhythmias is further substantiated by the protective effects of beta blockers both against myocardial ischemia and necrosisi3s14 and cardiac arrhythmias. 15.1h In human hearts no enhanced cardiac release of noradrenaline during coronary angioplastyinduced ischemia could be detected by sampling of coronary sinus blood.17 An association between ischemia and arrhythmias in humans was demonstrated by Garan et al’s in 17 patients with multivessel disease who survived out-ofhospital cardiac arrest. Before bypass surgery all developed VT during pacing-induced ischemia; after surgery VT or VF could not be induced in 10 patients, suggesting that ischemia was a major contributing factor for arrhythmia in these patients. Morady et al’” performed electrophysiological stimulation in 15 survivors