INCREASED FORMATION OF INTERSTITIAL HYDROXYL RADICAL FOLLOWING MYOCARDIAL-ISCHEMIA - POSSIBLE RELATIONSHIP TO ENDOGENOUS OPIOID-PEPTIDES

The effects of myocardial ischemia and reperfusion on interstitial hyd roxyl radical production, in the left ventricular myocardium of anesth etized cats, were investigated. Ringer's solution containing salicylic acid was perfused through an implanted microdialysis probe. Hydroxyl radical production was evaluated as the 2,3 and 2,5 dihydroxybenzoic a cid (DHBA) concentrations in the microdialysates by an on-line high pe rformance liquid chromatography system. Myocardial ischemia for 60 min , induced by ligation of the left anterior descending coronary artery, significantly increased both 2,3 and 2,5 DHBA levels when compared wi th the sham-operated cats. Naloxone (1 mg/kg, bolus, intravenous), an endogenous opioid peptide receptor antagonist, significantly suppresse d the ischemia-induced production of hydroxyl radicals. Myocardial isc hemia also induced cardiac arrhythmia. Naloxone reduced the severity o f ischemia-induced arrhythmia, as observed by a significantly lower ar rhythmia score (1.4 +/- 0.2 vs. 4.6 +/- 0.4 for control), and by dimin ished incidence of ventricular tachycardia (0/7 vs. 8/8 for control) a nd ventricular fibrillation (0/7 vs. 3/8 for control). Furthermore, pe rfusion of dynorphin (0.25 mu g, 2.5 mu g and 25 mu g), an endogenous opioid peptide receptor agonist, increased hydroxyl radical production . Our results suggest that, in anesthetized cats, myocardial ischemia can induce production of interstitial hydroxyl radical in left ventric ular myocardium, and this production may involve the actions of releas ed endogenous opioid peptides on their receptors.