acetylstrophanthidin and Ventricular-Fibrillation

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.

Topics: Aequorin; Animals; Calcium; Electric Stimulation; Electrophysiology; Ferrets; In Vitro Techniques; Male; Myocardial Contraction; Myocardium; Perfusion; Ryanodine; Sodium; Strophanthidin; Ventricular Fibrillation

Topics: Animals; Blood Circulation; Coronary Vessels; Dogs; Heart; Metabolism; Myocardium; Oxygen Consumption; Pharmacology; Research; Strophanthidin; Strophanthins; Vascular Resistance; Ventricular Fibrillation

Topics: Cardiovascular Diseases; Humans; Strophanthidin; Strophanthins; Ventricular Fibrillation

Topics: Administration, Intravenous; Cardiovascular Diseases; Digitalis; Digitalis Glycosides; Humans; Strophanthidin; Ventricular Fibrillation