Interaction of halogenated anesthetics with α- and β-adrenoceptor stimulations in diabetic rat myocardium

Abstract

Background: Halogenated anesthetics potentiate the positive inotropic effects of α- and β-adrenoceptor stimulations. Although diabetes mellitus induces significant myocardial abnormalities, the interaction of halogenated anesthetics and adrenoceptor stimulation in diabetic myocardium remains unknown. Methods: Left ventricular papillary muscles were provided from healthy and streptozotocin-induced diabetic rats. Effects of 1 minimum alveolar concentration halothane, isoflurane, and sevoflurane on the inotropic and lusitropic responses of α (phenylephrine)- and β (isoproterenol)- adrenoceptor stimulations were studied at 29°C with 12 pulses/min. Data shown are mean percentage of baseline active force ± SD. Results: Phenylephrine induced comparable positive inotropic effects in healthy and diabetic rats (143 ± 8 vs. 136 ± 18%; not significant), but the potentiation by halogenated anesthetics was abolished in the diabetic rats (121 ± 20, 130 ± 20, and 123 ± 20% for halothane, isoflurane, and sevoflurane, respectively; not significant). In diabetic rats, the positive inotropic effect of isoproterenol was markedly diminished (109 ± 9 vs. 190 ± 18%; P < 0.05), but its potentiation was preserved with isoflurane (148 ± 21%; P < 0.05) and sevoflurane (161 ± 40%; P < 0.05) but not with halothane (126 ± 16%; not significant). Halothane induced a deleterious effect on the sarcoplasmic reticulum, as shown by its impairment in the lusitropic effect of isoproterenol, compared with isoflurane and sevoflurane. Conclusion: Potentiation of the positive inotropic effect of α-adrenoceptor stimulation by halogenated anesthetics is abolished in diabetic rats. In contrast, potentiation of β-adrenoceptor stimulation is preserved with isoflurane and sevoflurane but not with halothane, probably because of its deleterious effects on sarcoplasmic reticulum.