Role of Calcium and the Calcium Channel in the Initiation and Maintenance of Ventricular Fibrillation

• Published in: Circulation research 1990-11, Vol.67 (5), p.1115-1123
• Main Authors: Merillat, John C, Lakatta, Edward G, Hano, Osamu, Guarnieri, Thomas
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Biological Transport, Active; Calcium - metabolism; Calcium Channels - metabolism; Cardiac dysrhythmias; Cardiology. Vascular system; Electric Countershock; Heart; In Vitro Techniques; Medical sciences; Nitrendipine - pharmacology; Potassium - metabolism; Rabbits; Sarcoplasmic Reticulum - metabolism; Ventricular Fibrillation - metabolism; Ventricular Fibrillation - therapy; Verapamil - pharmacology
• ISSN: 0009-7330; 1524-4571
• DOI: 10.1161/01.res.67.5.1115

The cellular events during the initiation and maintenance of ventricular fibrillation (VF) are poorly understood. We developed a nonischemic, isolated, perfused rabbit Langendorff preparation in which sustained VF could be induced by alternating current (AC) and which allowed changes in perfusate composition. We also used Na-K pump inhibition (10 μM ouabain or K-free perfusate) to induce VF. AC stimulation or Na-K pump inhibition always initiated VF. Calcium channel blockade by verapamil or nitrendipine uniformly inhibited the initiation of VF in both models. During Na-K pump inhibition, 1) VF was prevented by calcium channel blockade, despite evidence of Ca overload, and 2) abolition of spontaneous sarcoplasmic reticulum-generated cytosolic Ca oscillations by ryanodine or Na channel blockade with tetrodotoxin did not prevent VF initiation. Lowering extracellular [Ca] to 80 μM uniformly prevented the initiation of VF due to Na-K pump inhibition but not that due to AC stimulation. VF maintenance also was studied using 1) reduction in perfusate [Ca], 2) blockade of Ca channels, or 3) electrical defibrillation. Decreasing the perfusate [Ca] to 80 μM resulted in defibrillation during VF whether induced by AC or Na-K pump inhibition. Verapamil or nitrendipine also resulted in defibrillation regardless of the initiation method. Electrical defibrillation was successful only in AC-induced VF. The results demonstrate that VF can be initiated and maintained in a nonischemic rabbit Langendorff preparation. The data suggest that increases in slow channel Ca flux, as opposed to increases in cytosolic Ca per se, were necessary for the initiation and maintenance of VF. The data, however, do not exclude an important role for cytosolic Ca in the modulation of VF.