Parecoxib inhibits apoptosis in acute myocardial infarction due to permanent coronary ligation but not due to ischemia-reperfusion.
OBJECTIVE
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.
Salloum
Fadi N
FN
Division of Cardiology, Pauley Heart Center, Virginia Commonwealth University, Richmond, VA 23298-0281, USA.
Hoke
Nicholas N
NN
Seropian
Ignacio M
IM
Varma
Amit
A
Ownby
Evan D
ED
Houser
Jon-Erik
JE
Van Tassell
Benjamin W
BW
Abbate
Antonio
A
D000208:Acute Disease; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D023921:Coronary Stenosis / Q000150:complications*; D003331:Coronary Vessels; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D004452:Echocardiography; D007274:Injections, Intraperitoneal; D007555:Isoxazoles / Q000494:pharmacology* / Q000627:therapeutic use; D008026:Ligation; D008297:Male; D051379:Mice; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D009206:Myocardium / Q000473:pathology; D020257:Ventricular Remodeling / Q000187:drug effects
D052246:Cyclooxygenase 2 Inhibitors; D007555:Isoxazoles; C409945:parecoxib