Circ Res. 1990 Nov;67(5):1115-23. doi: 10.1161/01.res.67.5.1115.

Role of calcium and the calcium channel in the initiation and maintenance of ventricular fibrillation.

Circulation research

J C Merillat, E G Lakatta, O Hano, T Guarnieri

PMID: 2171799 DOI: 10.1161/01.res.67.5.1115

Abstract

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 microM 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 Ca2+ overload, and 2) abolition of spontaneous sarcoplasmic reticulum-generated cytosolic Ca2+ oscillations by ryanodine or Na+ channel blockade with tetrodotoxin did not prevent VF initiation. Lowering extracellular [Ca2+] to 80 microM 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 [Ca2+], 2) blockade of Ca2+ channels, or 3) electrical defibrillation. Decreasing the perfusate [Ca2+] to 80 microM 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 Ca2+ flux, as opposed to increases in cytosolic Ca2+ per se, were necessary for the initiation and maintenance of VF. The data, however, do not exclude an important role for cytosolic Ca2+ in the modulation of VF.

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Cited by

Substances

• Calcium Channels
• Nitrendipine
• Verapamil
• Potassium
• Calcium

MeSH terms

• Animals
• Biological Transport, Active
• Calcium / metabolism
• Calcium Channels / metabolism
• Electric Countershock
• In Vitro Techniques
• Nitrendipine / pharmacology
• Potassium / metabolism
• Rabbits
• Sarcoplasmic Reticulum / metabolism
• Ventricular Fibrillation / metabolism
• Ventricular Fibrillation / therapy
• Verapamil / pharmacology

Publication Types

• Comparative Study
• Journal Article
• Research Support, U.S. Gov't, P.H.S.

Grant support

• HL-17655/HL/NHLBI NIH HHS/United States
• HL-38210/HL/NHLBI NIH HHS/United States

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