Increased formation of interstitial hydroxyl radical following myocardial ischemia: possible relationship to endogenous opioid peptides.
The effects of myocardial ischemia and reperfusion on interstitial hydroxyl radical production, in the left ventricular myocardium of anesthetized 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 acid (DHBA) concentrations in the microdialysates by an on-line high performance 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 with the sham-operated cats. Naloxone (1 mg/kg, bolus, intravenous), an endogenous opioid peptide receptor antagonist, significantly suppressed the ischemia-induced production of hydroxyl radicals. Myocardial ischemia also induced cardiac arrhythmia. Naloxone reduced the severity of ischemia-induced arrhythmia, as observed by a significantly lower arrhythmia score (1.4 +/- 0.2 vs. 4.6 +/- 0.4 for control), and by diminished incidence of ventricular tachycardia (0/7 vs. 8/8 for control) and ventricular fibrillation (0/7 vs. 3/8 for control). Furthermore, perfusion of dynorphin (0.25 microgram, 2.5 micrograms and 25 micrograms), 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 ventricular myocardium, and this production may involve the actions of released endogenous opioid peptides on their receptors.
Yang
C S
CS
Department of Medical Research, Taichung Veterans General Hospital, Taiwan, R.O.C.
Tsai
P J
PJ
Chen
W Y
WY
Kuo
J S
JS
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D002415:Cats; D005841:Gentisates; D006321:Heart / Q000187:drug effects; D062385:Hydroxybenzoates / Q000378:metabolism; D017665:Hydroxyl Radical / Q000378:metabolism*; D008297:Male; D017551:Microdialysis; D017202:Myocardial Ischemia / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000378:metabolism*; D009270:Naloxone / Q000494:pharmacology*; D012016:Reference Values; D017180:Tachycardia, Ventricular / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*
D005841:Gentisates; D062385:Hydroxybenzoates; D017665:Hydroxyl Radical; D009270:Naloxone; C009135:2,3-dihydroxybenzoic acid; C010925:2,5-dihydroxybenzoic acid