Effects of β-Blockade on the Incidence of Ventricular Tachyarrhythmias during Acute Myocardial Ischemia: Experimental Findings and Clinical Implications

Myocardial ischemia and infarction are the most common substrates for life-threatening ventricular tachyarrhythmias. Experimental and clinical evidence suggests that enhanced activity of the sympathetic nervous system plays an important role in the genesis of ischemia-related arrhythmias. In animal experiments, beta-blockers display significant antifibrillatory effects during the acute phase of myocardial ischemia. Preconditions for their antifibrillatory effects are high serum- and tissue-concentrations, and absence of a significant partial agonist activity. During the delayed phase of ischemic arrhythmias which starts 6-8 h after coronary occlusion, beta-blockers gain significance as antiarrhythmic and potentially antifibrillatory drugs, if sympathetic activity is enhanced. The presently available evidence suggests that the potentially antifibrillatory effects of beta-blockers are at least one of the major mechanisms by which these drugs may decrease mortality when given prophylactically in patients after myocardial infarction. However, it remains to be explained why beta-blockers, in a great number of prospective randomized trials, have reduced the incidence of sudden death only by an average of about 30%. This may be the result of their "specific" mechanisms acting in the setting of acute myocardial ischemia with enhanced adrenergic tone, whereas in the remaining patients other mechanisms such as a chronic arrhythmogenic substrate may be operative. A clearer separation of these various mechanisms seems mandatory in order to allow a more specific "targeted" administration of beta-blockers. This is the more important since none of the available prospective studies that used antiarrhythmic agents has shown an improvement of prognosis, but, instead showed a worsening of the mortality rate.