Electrophysiological mechanisms for the initiation and maintenance of ventricular fibrillation in nonischemic rabbit hearts.

Abstract

Two series of experiments were carried out using isolated, perfused rabbit hearts to elucidate the mechanisms of initiation and maintenance of ventricular fibrillation in the absence of ischemia. In the first series, either single premature or rapid electrical stimulation induced ventricular fibrillation, during which the spread of excitation was studied by recording electrograms from the endocardial and epicardial surfaces of both ventricles. Left ventricular endocardial stimulation appeared to induce fibrillation most easily. Initiation of ventricular fibrillation was preceded by the spread of areas showing a conduction delay. In certain instances, excitation of the endocardial and subendocardial tissue was necessary for the maintenance of repetitive responses. Injury to the endocardial and subendocardial layers of a ventricle (or both ventricles) by formaldehyde perfusion made the initiation of fibrillation more difficult, although complete prevention of fibrillation required extensive injury with a significant reduction in the excitable myocardial mass. In the second series of experiments, sustained ventricular fibrillation was produced by rapid electrical stimulation and the effects of several antiarrhythmic agents or electrolytes were studied by recording transmembrane action potentials of subepicardial ventricular muscle fibers with microelectrodes. Quinidine, lidocaine, and high K+ concentration significantly decreased the frequency of cellular depolarization and terminated fibrillation in all the 14 hearts studied. These agents suppressed local responses and small action potentials, and made the action potentials more uniform. In 5 of the 14 hearts in these three groups, termination of fibrillation was followed by either transient or prolonged periods of regular ventricular tachycardia. High Mg2+ concentration and bretylium tosylate tended to hyperpolarize the cell membrane, but less markedly decreased the frequency of cellular discharge. Defibrillation was achieved in only two of the ten hearts in which these two interventions were tested. Lanatoside C shortened the action potential duration, sometimes increased the frequency of cellular depolarization, and tended to sustain fibrillatory movements. These observations suggest the role of numerous microreentry movements in both the initiation and maintenance of ventricular fibrillation, although unifocal, ectopic impulse formation may not be definitely ruled out as an initiating mechanism. The possible defibrillating effect of certain antiarrhythmic agents is suggested.