Intracellular calcium and ventricular fibrillation. Studies in the aequorin-loaded isovolumic ferret heart.
To elucidate the role of changes in [Ca2+]i in the induction of ventricular fibrillation (VF), Ca2+i signals, epicardial electrical potentials, and isovolumic left ventricular pressure were simultaneously recorded in isolated intact ferret hearts loaded with aequorin, a bioluminescent protein. When the preparations were perfused with 3 microM acetylstrophanthidin and 8 mM Ca2+, or with a low Na+ solution (18 mM Na+, 100 mM Li+), spontaneous transitions to the VF state were consistently observed within a short period of time. The initiation of spontaneous VF was preceded by development of a Ca2+i overload state, coincidental with the ascending phase of diastolic Ca2+i oscillations, and was followed by further elevation in Ca2+i levels, which were associated with augmented Ca2+i oscillations of a saw-toothed pattern. Pretreatment with 10 microM ryanodine, which blocked Ca2+i oscillations in the preparation, did not eliminate inducibility of VF by means of AC electrical stimulations; however, VF no longer occurred spontaneously, and the threshold for VF induction increased markedly. In the absence of a state of Ca2+i overload, spontaneous defibrillation occurred within a minute after the initiation of VF. We conclude that 1) VF can be induced in the absence of Ca2+i oscillations; however, 2) Ca2+i oscillations play a crucial role as a trigger for VF and therefore are an important determinant of the vulnerability to VF; and 3) the augmented Ca2+i oscillations after the transition to VF state may support the maintenance of this type of arrhythmia.
Kihara
Y
Y
Charles A. Dana Research Institute, Boston, Mass.
Morgan
J P
JP
D000331:Aequorin; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D004558:Electric Stimulation; D004594:Electrophysiology; D005289:Ferrets; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism*; D010477:Perfusion; D012433:Ryanodine / Q000494:pharmacology; D012964:Sodium / Q000378:metabolism; D013327:Strophanthidin / Q000031:analogs & derivatives / Q000494:pharmacology; D014693:Ventricular Fibrillation / Q000209:etiology* / Q000378:metabolism
D012433:Ryanodine; D000331:Aequorin; D013327:Strophanthidin; D012964:Sodium; C004681:acetylstrophanthidin; D002118:Calcium