Interaction of halothane with α- and β-adrenoceptor stimulations in rat myocardium

Abstract

Background: Halothane induces negative inotropic and lusitropic effects in myocardium. It has been suggested that halothane potentiates β- adrenoceptor stimulation. However, its effects on the inotropic response to α-adrenoceptor stimulation and its effects on the lusitropic effects of α- and β-adrenoceptor stimulation are unknown. Methods: The effects of halothane (0.5 and 1 minimum alveolar concentration [MAC]) on the inotropic responses induced by phenylephrine (10-8 to 10-4 M) and isoproterenol (10-8 to 10-4 M) were studied in rat left ventricular papillary muscles in vitro (in Krebs-Henseleit solution at 29°C, pH 7.40, with 0.5 mM calcium and stimulation frequency at 12 pulses/min). The lusitropic effects were studied in isotonic (R1) and isometric (R2) conditions. Results: One MAC halothane induced a negative inotropic effect (54 ± 3%, P < 0.05), increased R1 (109 ± 3%, P < 0.05), and decreased R2 (88 ± 2%, P < 0.05). In control groups, phenylephrine (137 ± 70%, p > 0.05) and isoproterenol (162 ± 6%, P < 0.05) induced a positive inotropic effect. Halothane did not significantly modify the positive inotropic effect of calcium, suggesting that it did not modify the inotropic reserve of papillary muscles. In contrast, 1 MAC halothane enhanced the positive inotropic effects of phenylephrine (237 ± 19%, P < 0.05) and isoproterenol (205 ± 11%, P < 0.05). Halothane did not modify the lusitropic effect of phenylephrine under high or low load. In contrast, 1 MAC halothane impaired the positive lusitropic effect of isoproterenol under low load (P < 0.05), whereas it did not modify the positive lusitropic effect of isoproterenol under high load. Conclusions: At clinically relevant concentrations, halothane potentiated the positive inotropic effects of both α- and β-adrenoceptor stimulation. Furthermore, halothane alters the positive lusitropic effect of β-adeenoceptor stimulation under low load.