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

We investigated the effects of PR-39, a recently discovered neutrophil inhi bitor, in a murine model of myocardial ischemia-reperfusion injury. Mice we re 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 reperf usion. 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) red uced in PR-39 treated hearts (21.0 +/- 3.8%) compared with vehicle (47.1 +/ - 4.8%). Histological analysis of ischemic reperfused myocardium demonstrat ed a significant (P, 0.01) reduction in polymorphonuclear neutrophil (PMN) accumulation in PR-39-treated hearts (n = 6, 34.3 +/- 1.7 PMN/mm(2)) compar ed with vehicle-treated myocardium (n = 6, 59.7 +/- 3.1 PMN/mm(2)). In addi tion, PR-39 significantly (P < 0.05) attenuated leukocyte rolling and adher ence in rat inflamed mesentery. These results indicate that PR-39 inhibits leukocyte recruitment into inflamed tissue and attenuated myocardial reperf usion injury in a murine model of myocardial ischemia-reperfusion.