Parecoxib inhibits apoptosis in acute myocardial infarction due to permanent coronary ligation but not due to ischemia-reperfusion.

Abstract

PURPOSE:

Myocardial ischemia induces cyclooxygenase 2 (COX-2) expression. We evaluated the effects of parecoxib, a COX-2 inhibitor, in 2 different mouse models of myocardial ischemia: permanent left coronary artery ligation (PI) and transient ligation (30 minutes ischemia) followed by reperfusion (I/R).

METHODS:

Forty adult male Institute of Cancer Research mice underwent PI (n = 24) or I/R (n = 16), followed by randomization to parecoxib (0.75 mg/kg intraperitoneal daily) or normal saline for 7 days.

RESULTS:

Parecoxib significantly reduced apoptosis [0.8% vs. 3.4% (saline), P < 0.001] and 7-day mortality [0% vs. 57% (saline), P = 0.040] in the PI group but showed no benefit in the I/R group. Parecoxib-treated mice also exhibited greater fractional shortening in the PI group [22% vs. 14% (saline), P = 0.045) but not in the I/R group. Parecoxib did not affect infarct size in either group.

CONCLUSIONS:

COX-2 may play a pivotal role in mediating apoptosis in the ischemic peri-infarct myocardium that is not reperfused after infarct.

• Authors: Fadi N Salloum, Nicholas N Hoke, Ignacio M Seropian, Amit Varma, Evan D Ownby, Jon-Erik Houser, Benjamin W Van Tassell, Antonio Abbate
• Journal: Journal of cardiovascular pharmacology (J Cardiovasc Pharmacol) Vol. 53 Issue 6 Pg. 495-8 (Jun 2009) ISSN: 1533-4023 [Electronic] United States
• PMID: 19455055 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cyclooxygenase 2 Inhibitors
• Isoxazoles
• parecoxib

Topics

• Acute Disease
• Animals
• Apoptosis (drug effects)
• Coronary Stenosis (complications)
• Coronary Vessels
• Cyclooxygenase 2 Inhibitors (pharmacology, therapeutic use)
• Disease Models, Animal
• Echocardiography
• Injections, Intraperitoneal
• Isoxazoles (pharmacology, therapeutic use)
• Ligation
• Male
• Mice
• Myocardial Infarction (drug therapy, etiology, pathology)
• Myocardial Reperfusion Injury (complications, drug therapy, pathology)
• Myocardium (pathology)
• Ventricular Remodeling (drug effects)