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

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.

Calcium antagonistic and antiarrhythmic actions of CPU‐23, a substituted tetrahydroisoquinoline

“…The reduction in force of contraction of the isolated perfused heart has been well established as resulting from inhibition of transmembrane calcium influx through the L-type calcium channels (Fleckenstein, 1977;Conti et al, 1985). More calcium which is required for the initiation and maintenance of VF (Merillat et al, 1990) by binding to dihydropyridinesensitive calcium channels. In short the findings of the present study support the view that the antiarrhythmic action of CPU-23 may be due primarily to an inhibition of transmembrane calcium influx in the cardiac tissue as suggested by Curtis & Walker (1988) and Lydtin & Trenkwalder (1990).…”

Spatiotemporal Relationship Between Intracellular Ca 2+ Dynamics and Wave Fragmentation During Ventricular Fibrillation in Isolated Blood-Perfused Pig Hearts

“…36 Others demonstrated that manipulations leading to Ca i overload readily induced VF. 37,38 Those studies, however, did not provide definitive data as to the role of Ca i oscillations in the maintenance of VF (this topic is discussed in Ref. 14).…”

Life Span of Ventricular Fibrillation Frequencies

“…13,14 Time-frequency analysis was applied to better understand and visualize how a Ca 2ϩ channel blocker influences the behavior of VF dynamics in time and space. Nifedipine (2 mol/L) was added during VF, and transmembrane potentials were recorded continuously for 5 minutes for time-frequency analysis.…”