A vertical approach to cardiac arrhythmias.

Study of cardiac arrhythmia may be pursued vertically, as up the rungs of a ladder, from symptom to ECG, to EPS, to local lesion, to intracellular metabolism and to alterations of the latter and their effects on charge-transfer by ions across the cell membrane. Raised intracellular cAMP and calcium concentrations are responses to normal physiological controls, and highly abnormal ECGs occur in normal people under stress without progressing to life threatening arrhythmias, yet do so in susceptible individuals. Conversely, appropriate stimulation can precipitate ventricular fibrillation in normal myocardium. Selective stimulation of different types of adrenoceptor has differing electrophysiological effects. Beta 1-adrenoceptors increase contraction and calcium current, and shorten action potential duration (APD) by increasing potassium conductance. Beta 2-adrenoceptors do not increase calcium entry, but shorten APD by stimulating electrogenic Na/K pumping, alpha-adrenoceptors prolong contractions and lengthen APD. It is suggested that the tachycardia, extrasystoles and shortening of APD occurring in response to adrenergic stimuli and hypoxia, are accessory factors, not primary causes, in the development of arrhythmias, and constitute a danger when there is an appropriate anatomical substrate for re-entry. Serious arrhythmias are of multifactorial origin, of which "calcium overload" is but one, not proven to be a frequent one.