Role of catecholamines in the genesis of arrhythmias.

Catecholamines play a major role in the induction of cardiac rhythm disorders. The effects of catecholamines are caused by activation of beta-receptors in the heart and appear to be mediated by the cyclic AMP/protein kinase system. Increased rate of spontaneous diastolic depolarization of cardiac fibers on exposure to endogenous or exogenous catecholamine activity leads to tachyarrhythmias. Because of non-uniform distribution of sympathetic nerve endings, activation of the sympathetic nerve system may result in non-uniform reduction in the refractory period leading to re-entrant excitation. Under abnormal conditions myocardium may become more sensitive to catecholamines. In ischemia, sympathetic stimulation causes more local differences in refractory period and a greater tendency to fibrillate. Following acute coronary ligation there is a direct relationship between rhythm disturbance and levels of myocardial catecholamines. Catecholamines not only cause arrhythmia but also contribute to the development of digitalis-induced arrhythmias. The role of catecholamines in the genesis of certain cardiac arrhythmias is further supported by the fact that beta-blocking drugs which antagonize sympathetic activity are effective for treating various types of acute arrhythmias and for prevention of recurrent arrhythmias.