Effect of calcium on strophanthidin-induced electrical and mechanical toxicity in cardiac Purkinje fibers.
The role of calcium in the electrical and mechanical toxicity induced by strophanthidin (10(-6) M) was studied in canine Purkinje fibers perfused in vitro. Strophanthidin caused an increase in contractile force ("therapeutic effect") followed by a subsequent decrease and by the onset of arrhythmias ("toxic effects"). The onset of arrhythmias occurred sooner in low- and later in high-calcium solutions with respect to the normal calcium. The positive inotropic (therapeutic) effect of strophanthidin was reduced or prevented by caffeine (1 mM) or by high calcium. The late (toxic) decline in force during exposure to strophanthidin was temporarily reversed by decreasing [Ca]o to a low value. Similarly, the contractile force decreased when [Ca]o was increased from 8.1 to 16.2 mM and this decline was transiently reversed when [Ca]o was reduced to a low value. It is concluded that in Purkinje fibers 1) electrical toxicity may occur independently of an intracellular calcium accumulation, and 2) the mechanical toxicity may be due to an excessive accumulation of calcium in the fiber.
D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D006329:Heart Conduction System / Q000502:physiology*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects*; D009200:Myocardial Contraction / Q000187:drug effects; D011690:Purkinje Fibers / Q000502:physiology*; D013327:Strophanthidin / Q000037:antagonists & inhibitors*; D013806:Theophylline / Q000494:pharmacology
D002110:Caffeine; D013327:Strophanthidin; D013806:Theophylline; D002118:Calcium