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: M R Hoffmeyer, R Scalia, C R Ross, S P Jones, D J Lefer
• Journal: American journal of physiology. Heart and circulatory physiology (Am J Physiol Heart Circ Physiol) Vol. 279 Issue 6 Pg. H2824-8 (Dec 2000) ISSN: 0363-6135 [Print] United States
• PMID: 11087237 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Anti-Bacterial Agents
• Antimicrobial Cationic Peptides
• Hemostatics
• Reactive Oxygen Species
• PR 39
• Thrombin

Topics

• Animals
• Anti-Bacterial Agents (pharmacology)
• Antimicrobial Cationic Peptides (pharmacology)
• Cell Adhesion (drug effects, immunology)
• Coronary Vessels (surgery)
• Hemostatics (pharmacology)
• Ileum (immunology, metabolism)
• Ligation
• Male
• Mice
• Mice, Inbred Strains
• Microscopy (methods)
• Myocardial Infarction (drug therapy, immunology)
• Myocardial Reperfusion Injury (drug therapy, immunology)
• Myocardium (immunology, metabolism)
• Neutrophils (cytology, drug effects, immunology)
• Rats
• Rats, Sprague-Dawley
• Reactive Oxygen Species (metabolism)
• Thrombin (pharmacology)