Calcium oscillations in digitalis-induced ventricular fibrillation: pathogenetic role and metabolic consequences in isolated ferret hearts.
The pathophysiology of the ventricular fibrillation that complicates digitalis intoxication was investigated. In this and other calcium-overload states, oscillations of the intracellular free calcium concentration ([Ca2+]i) have been implicated as the cause of ventricular tachyarrhythmias. We addressed two questions: 1) Are [Ca2+]i oscillations obligatory in the pathogenesis of ventricular fibrillation during digitalis toxicity? 2) What are the metabolic consequences of [Ca2+]i oscillations? Ferret hearts (n = 20) were Langendorff-perfused at constant flow with oxygenated HEPES-buffered Tyrode's solution at 37 degrees C. Isovolumic left ventricular pressure was measured along with the extracellular electrogram or with simultaneous phosphorus nuclear magnetic resonance spectra. When strophanthidin (20 microM) was added during pacing at 3 Hz, the positive inotropic effect soon gave way to a decrease in developed force. The decrease in force was accompanied by an increase in inorganic phosphate concentration, a decrease in phosphocreatine concentration, and a slight acidosis. The rhythm changed to ventricular fibrillation after 12-25 minutes. This change was initially accompanied by further metabolic deterioration, but all metabolites reached steady state within 12-18 minutes of the onset of ventricular fibrillation. Fast Fourier transformation revealed the existence of periodic oscillations at 7-10 Hz in both the extracellular electrogram and the ventricular pressure during ventricular fibrillation. Ryanodine, an inhibitor of [Ca2+]i oscillations, abolished the pressure oscillations but not the voltage oscillations. Exposure to ryanodine significantly decreased the inorganic phosphate concentration and increased the phosphocreatine concentration (p less than 0.05) despite continuing exposure to strophanthidin. The results indicate that oscillations of [Ca2+]i are not required to sustain ventricular fibrillation, but when present, such oscillations contribute importantly to metabolic deterioration.
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D004562:Electrocardiography; D005289:Ferrets; D005583:Fourier Analysis; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D012433:Ryanodine / Q000494:pharmacology; D013327:Strophanthidin / Q000633:toxicity*; D014693:Ventricular Fibrillation / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology
D007473:Ion Channels; D012433:Ryanodine; D013327:Strophanthidin; D002118:Calcium