Digitalis-induced mechanical toxicity: protection by slow Ca++ channel blockers.
In the in vitro perfusion of the isolated heart, toxic doses of cardiac glycosides produce an inotropic response which is followed by a decline in contractile force and an increase in the resting tension. Several reports in the literature indicate that the subsequent decline in contractile force may be related to cardiac cellular Ca++ overload. The purpose of the present study was to determine if the slow Ca++ channel blockers such as verapamil and nifedipine, which block Ca++ influx through voltage-dependent gated channels, can reduce or prevent the digitalis-induced decline in contractile force (mechanical toxicity). Langendorff preparations of isolated perfused guinea pig heart were used for the present study. The data obtained demonstrate that 1 to 2 microM ouabain in the perfusion medium produced mechanical toxicity in the hearts after an initial inotropic response. Verapamil or nifedipine, when combined with ouabain in the perfusion medium, increased the magnitude of the inotropic response and delayed or abolished the mechanical toxicity in a dose-dependent manner. No changes in the sarcolemmal Na+,K+-adenosine triphosphatase or ouabain binding were observed in the presence of verapamil or nifedipine. The data suggest that simultaneous use of verapamil or nifedipine may protect against digitalis-induced mechanical toxicity.
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002301:Cardiac Glycosides / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects; D006352:Heart Ventricles / Q000187:drug effects; D009543:Nifedipine / Q000494:pharmacology; D010042:Ouabain / Q000494:pharmacology; D010477:Perfusion; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013327:Strophanthidin / Q000633:toxicity; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D002301:Cardiac Glycosides; D010042:Ouabain; D013327:Strophanthidin; D014700:Verapamil; D000254:Sodium-Potassium-Exchanging ATPase; D009543:Nifedipine