Effects of halothane on arrhythmias induced by myocardial ischaemia

Abstract

Effects of halothane on arrhythmias induced by myocardial ischaemiaThe effect of halothane on arrhythmias induced by ischaemia was investigated in rats, isolated perfused rat hearts, and pigs. Responses to the occlusion of the left anterior descending coronary artery were determined in groups (n = 9) of chronically prepared rats" treated with no halothane, 0. This laboratory has previously reported that halothane anaesthesia diminished ischaemia-induced arrhythmias when compared with pentobarbital anaesthesia. ~,2 Subsequently we showed that ischaemia-induced arrhythmias were also reduced in incidence, severity, and duration by halothane when compared with conscious rats or rats receiving fentanyl anaesthesia) This antiarrhythmic action of halothane was dose-dependent, and was much greater than other halogenated anaesthetics (methoxyflurane, enflurane, isoflurane, chloroform) thus demonstrating that halothane reduced severe arrhythmias independently of the anaesthetic state. 4 Other workers have demonstrated that halothane has antiarrhythmic actions against ischaemic arrhythmias in dogs. 5'6 However, the mechanism of halothane's antiarrhythmic action in rats and dogs remains unknown and the clinical significance of the findings uncertain 4,6,7To investigate the mechanism of action and the clinical relevance of the antiarrhythmic actions of halothane, we addressed the following questions.(1) Does halothane have antiarrhythmic actions when administered after coronary artery occlusion? If so, similar compounds should be investigated as a possible treatment for ischaemic arrhythmias, independent of their anaesthetic actions, and to provide clues into the mechanism of arrhythmogenesis. The time of onset of the antiarrhythmic action also helps to determine if the drug is acting in the perfused, non-perfused or border regions of the ischaemic zone.(2) Does halothane have antiarrhythmic actions in isolated perfused hearts? Answers to this question help define mechanisms of antiarrhythmic action, i.e., does it involve direct mechanisms, or indirect ones mediated by the CNS, endocrine or cardiovascular systems.(3) Is the antiarrhythmic action species dependent? By testing for antiarrhythmic actions in the pig, a species with a similar cardiovascular system to man, the experimental f'mdings can be better extrapolated to man. 23 Methods Study I Post-occlusion halothane in chronically prepared ratsUnder halothane anaesthesia rats were prepared with a left