Reversible and irreversible forms of contractile failure caused by disturbances by general anesthetics in myocardial ATP utilization

Abstract

Overdoses of several volatile anesthetics (ether, chloroform, ethyl chloride, halothane, methoxyflurane) as well as of various barbiturates lead to severe contractile failure of the heart. In all cases it was found that at the stage of maximal failure the myocardial stores of ATP and phosphocreatine were increased, indicative of reduced high energy phosphate utilization. Barbiturate-induced failure can be fully reversed by the intravenous injection of CaCl2, isoproterenol, or strophanthin. Simultaneously ATP and phosphocreatine concentrations become normal. In contrast, cardiac failure caused by volatile anesthetics proved to be resistant to this therapy. Electron micrographs showed a normal structure of the transverse tubules in the case of barbiturate failure. On the other hand, after the application of volatile anesthetics, a striking dilatation of the transverse tubular system was observed. The irreversibility of this latter type of contractile failure is probably caused by permanent damage of myocardial ultrastructures involved in excitation-contraction coupling.