PR-39, a potent neutrophil inhibitor, attenuates myocardial ischemia-reperfusion injury in mice

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Abstract
We investigated the effects of PR-39, a recently discovered neutrophil inhibitor, in a murine model of myocardial ischemia-reperfusion injury. Mice were given an intravenous injection of vehicle ( n = 12) or PR-39 ( n = 9) and subjected to 30 min of coronary artery occlusion followed by 24 h of reperfusion. In addition, the effects of PR-39 on leukocyte rolling and adhesion were studied utilizing intravital microscopy of the rat mesentery. The area-at-risk per left ventricle was similar in vehicle- and PR-39-treated mice. However, myocardial infarct per risk area was significantly ( P < 0.01) reduced in PR-39 treated hearts (21.0 ± 3.8%) compared with vehicle (47.1 ± 4.8%). Histological analysis of ischemic reperfused myocardium demonstrated a significant ( P < 0.01) reduction in polymorphonuclear neutrophil (PMN) accumulation in PR-39-treated hearts ( n = 6, 34.3 ± 1.7 PMN/mm2) compared with vehicle-treated myocardium ( n = 6, 59.7 ± 3.1 PMN/mm2). In addition, PR-39 significantly ( P < 0.05) attenuated leukocyte rolling and adherence in rat inflamed mesentery. These results indicate that PR-39 inhibits leukocyte recruitment into inflamed tissue and attenuated myocardial reperfusion injury in a murine model of myocardial ischemia-reperfusion.