OXYGEN RADICALS RELEASED DURING ISCHEMIC PRECONDITIONING CONTRIBUTE TO CARDIOPROTECTION IN THE RABBIT MYOCARDIUM

Previous studies have proposed that oxygen radicals may play a role in the triggering of ischemic preconditioning. However, studies evaluati ng the effects of radical scavengers have yielded conflicting results, possibly because of differences in the number of preconditioning epis odes used. The present study tested whether N-2-mercaptopropionylglyci ne (MPG) could block protection of both single and multiple episodes o f preconditioning in in situ and in vitro rabbit hearts, All hearts we re subjected to 30 min of regional ischemia followed by reperfusion fo r 2 (in vitro) or 3 (in situ) h. Infarct size was measured by tetrazol ium. Infarction in control in situ hearts was 37.5+/-3.5% of the risk zone. A single cycle of preconditioning (PC1), with 5 min ischemia/10 min reperfusion, reduced infarct size to 12.3+/-2.0% (P<0.05). Four cy cles of preconditioning (PC4) were equally protective. MPG (1 mg/kg/mi n i.v.) alone had no effect on infarction but abolished protection aff orded by PC1 (35.4+/-3.9%). However, MPG failed to block protection in the PC4 group. In isolated control hearts, infarct size was 31.1+/-1. 8% and was reduced to 10.2+/-2.2% (P<0.05) by preconditioning. MPG (30 0 mu M) aborted protection. Infusion of hypoxanthine or xanthine oxida se separately in lieu of preconditioning had no effect on infarct size , but induced protection when combined (14.1+/-2.2%; P<0.05). Polymyxi n B, an inhibitor of protein kinase C (PKC), abolished this protection (53.1+/-4.1%). In conclusion, oxygen radicals contribute to ischemic preconditioning in the rabbit and appear to do so via activation of PI (C. The fact that MPG could not block protection by PC4 suggests that oxygen radicals act in concert with other triggers of preconditioning such as adenosine and bradykinin. (C) 1997 Academic Press Limited.