Effect of halothane on myocardial reoxygenation injury in the isolated rat heart

Several studies have reported a protective effect of halothane on myocardial injury in an ischaemia-reperfusion situation. It is unclear if the protection is a result of the haemodynamic effects of halothane or if halothane has a specific action on ischaemia or reperfusion pathomechanisms. To examine this question, we have used an isolated rat heart model where heart rate (300 beat min(-1)), ventricular volume and coronary flow are constant. Left ventricular developed pressure (LVDP) and release of creatine kinase (CK) were measured as variables of myocardial performance and cellular injury, respectively. Five control hearts were subjected to 35 min of low-flow (2 ml min(-1)) anoxic and substrate-free perfusion and were then perfused for 1 h with the oxygenated buffer. In the treatment groups, halothane 0.4 mmol litre(-1) was added during the first 30 min of anoxic perfusion (n = 5) or during the first 30 min of reoxygenation (n = 5), in five additional hearts, the effect of halothane 0.4 mmol litre(-1) was under normoxic tested conditions, Mean basal CK 0.29 (SEM 0.13) iu g(-1) min(-1) and 105.5 (4.0) mm Hg. Under normoxic conditions, halothane reduced LVDP to 52.0 (2.6) mm Hg. In control hearts, the major cell injury occurred at the onset of reoxygenation (CK release increased to 149.1 (9.1) iu g(-1) min(-1)) and functional recovery after 1 h of reoxygenation was poor (control LVDP, 14.2 (2.)% of baseline). Halothane during anoxia attenuated myocardial injury only moderately (CK release 50.2 (5.7) iu g(-1) min(-1)) and LVDP recovered to 30.8 (3.0)% (each P < 0.05 vs control). When halothane was administered at reoxygenation, CK release was reduced to 10.1 (0.9) iu g(-1) min(-1) and LVDP recovered to 69.4 (4.9)% (each P < .05 vs control). We conclude that halothane not only attenuated ischaemic injury but had a specific protective action against reoxygenation injury.