Halothane, Isoflurane and Enflurane Potentiate the Effect of Noradrenaline on Ventricular Automaticity in the Rat Heart: Evidence of the Involvement of Both α- and β-Adrenoceptors

Abstract

Direct evidence has been sought as to what extent the sensitization of heart to the arrhythmogenic action of sympathomimetic drugs in the presence of the inhalatory anaesthetics, halothane, isoflurane and enflurane, is mediated by either alpha- or beta-adrenoceptors. For this purpose, the effects of isoprenaline, noradrenaline and phenylephrine on ventricular automaticity induced by local injury have been studied in the isolated right ventricle of the rat. Isoprenaline was more potent in increasing ventricular automaticity than either phenylephrine or noradrenaline. The anaesthetic potentiated the effects of noradrenaline, as well as that of higher concentrations of phenylephrine, but not those of isoprenaline. These results support the contention that increases in ventricular automaticity induced by sympathomimetic drugs are mainly mediated by adrenoceptors of the beta-type. However, the simultaneous activation of both alpha- and beta-adrenoceptors seems to be necessary for the effect of the anaesthetics in sensitizing the heart to sympathomimetic drugs.

Effects of volatile anesthetics on cardiac ion channels

“…The cAMP-mediated modification of L-type Ca 2þ channels is a common end point of signaling by b-adrenergic stimulation and by inhibition of cAMP degradation (57) and explains the positive inotropic effects of b-adrenergic agonists and of phosphodiesterase inhibitors. It is textbook knowledge that the potentially arrhythmic effects of the sympathetic nervous system on the heart may be enhanced by halothane (7,58,59). However, the underlying mechanisms are mostly unclear.…”

Mechanisms Involved in Cardiac Sensitization by Volatile Anesthetics: General Applicability to Halogenated Hydrocarbons?

“…In some of these in vivo studies, the involvement of α 1 -and/or β 1 -adrenergic receptors in cardiac sensitization was also investigated (Claborn and Szabuniewicz, 1973;Maze and Smith, 1983;Tranquilli et al, 1986;Venugopalan et al, 1989). The involvement of both α-and β-adrenergic receptors in sensitization of the heart to catecholamines in the presence of halothane, enflurane, or isoflurane was also confirmed in vitro (Carceles et al, 1990).…”

“…Cardiac sensitization to the arrhythmogenic action of catecholamines in the presence of volatile anesthetics is attenuated by treatment with α-and/or β-adrenergic receptor antagonists (Maze and Smith, 1983;Carceles et al, 1990) and may involve deranged intracellular Ca 2+ handling (Roden et al, 2002). Both adrenergic and muscarinic receptor signaling may be important in this context since both couple to the adenylyl cyclase, via stimulatory G s or inhibitory G i proteins, and hence contribute to modulating the basal phosphorylation state of ion channels and other cellular proteins.…”