Morphine preconditioning attenuates neutrophil activation in rat models ofmyocardial infarction

Previous results from our laboratory have suggested that morphine can atten uate neutrophil activation in patients with acute myocardial infarction. To elucidate if morphine preconditioning (PC) has the same effects via activa tion of neutrophil endopeptidase 24.11 (NEP), we measured serum levels of i ntercellular adhesion molecule-1 (ICAM-1), gp100(MEL14) and NEP in adult Wi star rats subjected to ten different protocols (n=10 for each) at baseline, immediately after and 2 h after morphine PC. All groups were subjected to 30 min of occlusion and 2 h of reperfusion. Similarly, morphine-induced PC was elicited by 3-min drug infusions (100 mu g/kg) interspersed with 5-min drug-free periods before the prolonged 30-min occlusion. Infarct size (IS), as a percentage of the area at risk (AAR), was determined by triphenyltetr azolium staining. Pretreatment with morphine increased NEP activities (9.86 +/-1.98 vs. 5.12+/-1.10 nmol/mg protein in control group; p<0.001). Naloxon e (mu-opioid receptor antagonist) (4.82+/-1.02 nmol/mg protein) and phospho ramidon (NEP inhibitor) (4.66+/-1.00 nmol/mg protein) inhibited morphine-ac tivated NEP: whereas glibenclamide (ATP-sensitive potassium channel antagon ist) and chelerythrine (protein kinase C inhibitor) had no effects. The ICA M-1 and gp100MEL'4 Of the third sampling were lowest for those with morphin e PC (280+/-30 ng/ml and 2.2+/-0.7 mu g/ml; p<0.001), but naloxone (372+/-3 8 ng/ml and 3.8+/-0.9 mu g/ml) and phosphoramidon (382+/-40 ng/ml and 4.2+/ -1.1 mu g/ml) abolished the above phenomenon. IS/AAR were definitely lowest for those with morphine PC (24+/-7%; p <0.05). Morphine preconditioning in creases NEP activities to attenuate shedding of gp100(MEL14) and to ICAM-1 and, thus, provides myocardial protection. (C) 1998 Elsevier Science B.V. A ll rights reserved.