title: PR-39, a potent neutrophil inhibitor, attenuates myocardial ischemia-reperfusion injury in mice.
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/mm(2)) compared with vehicle-treated myocardium (n = 6, 59.7 +/- 3.1 PMN/mm(2)). 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.
authors.affiliation: Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, Louisiana 71130, USA.
authors.forename: M R
authors.initials: MR
authors.lastname: Hoffmeyer
authors.forename: R
authors.initials: R
authors.lastname: Scalia
authors.forename: C R
authors.initials: CR
authors.lastname: Ross
authors.forename: S P
authors.initials: SP
authors.lastname: Jones
authors.forename: D J
authors.initials: DJ
authors.lastname: Lefer
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects / Q000276:immunology; D003331:Coronary Vessels / Q000601:surgery; D006490:Hemostatics / Q000494:pharmacology; D007082:Ileum / Q000276:immunology / Q000378:metabolism; D008026:Ligation; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008853:Microscopy / Q000379:methods; D009203:Myocardial Infarction / Q000188:drug therapy / Q000276:immunology; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000276:immunology*; D009206:Myocardium / Q000276:immunology / Q000378:metabolism; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D013917:Thrombin / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D006490:Hemostatics; D017382:Reactive Oxygen Species; C072212:PR 39; D013917:Thrombin