Influence of halothane on the effect of cAMP-dependent and cAMP-independent positive inotropic agents in human myocardium

Volatile anaesthetics have a variety of effects on the myocardium, namely a negative inotropic effect and a catecholamine sensitizing effect. The present study was designed to see if the hydrocarbon anaesthetics interact specifically with subcellular targets of the myocardial cell, by examining the effects of halothane in the presence of positive inotropic agents with different mechanisms of action. Experiments were performed in isolated electrically driven left ventricular preparations (1 Hz, 37°C, Ca 2+ 1.8 mmol litre −1 ) from human hearts obtained at cardiac surgery. The concentration-response curves of noradrenaline, milrinone, BayK 8644 and Ca 2+ were investigated in the absence and in the presence of halothane. Halothane enhanced the efficacy of noradrenaline and milrinone but not of Ca 2+ or BayK 8644. The potency of milrinone was also increased by halothane, whereas the potency of BayK 8644 was decreased and those of noradrenaline and Ca 2+ were unchanged. Halothane differentially influences the effects of agents with different positive inotropic mechanisms. This experimental approach can be taken as a functional method to localize the mechanisms of action of the inhalation anaesthetics in human myocardium, namely sensitization of cAMP formation and interaction with L-type Ca 2+ channels.