Inhibition of COX pathway in experimental myocardial infarction.
Release of inflammatory mediators within the ischemic myocardium has long been thought to contribute to myocardial damage and dysfunction. Myocardial infarction (MI) and congestive heart failure (CHF) were induced in rats by ligating the left coronary artery. Animals were treated with the selective cyclooxygenase-2 (COX-2) inhibitor-5,5-dimethyl-3-(3-fluorophenyl1)-4-(4-methyl-sulphonyl-2(5H)-fluranone (DFU), low-, high-dose acetyl salicylic acid (aspirin), or vehicle for 3 months. Strong immunoreactivity for COX-2 was detected in the cardiomyocytes, vascular endothelial cells, and macrophages in the infarcted myocardium. Compared to the vehicle, treatment with DFU significantly reduced left ventricular end-diastolic pressure, central venous pressure, lung wet/dry ratio and infarct size, and improved cardiac contractility (P < 0.05). In comparison, treatment with low or high doses of aspirin did not significantly impact any of these parameters. These findings demonstrate that induction of myocardial COX-2 in rats with CHF secondary to MI contributes to the cardiac injury and dysfunction associated with this disease, and that therapy aimed at inhibiting this enzymatic pathway at the onset of the disease may be beneficial in the treatment of MI and CHF.
Saito
Takayuki
T
The Montreal General Hospital and McGill University, Montreal, Que., Canada H3G 1A4.
Rodger
Ian W
IW
Hu
Fu
F
Robinson
Richard
R
Huynh
Thao
T
Giaid
Adel
A
D000818:Animals; D001241:Aspirin / Q000494:pharmacology; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004195:Disease Models, Animal; D004452:Echocardiography; D004730:Endothelium, Vascular / Q000201:enzymology / Q000276:immunology; D005663:Furans / Q000494:pharmacology; D006333:Heart Failure / Q000201:enzymology; D006352:Heart Ventricles; D007150:Immunohistochemistry; D007249:Inflammation; D007527:Isoenzymes / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D009203:Myocardial Infarction / Q000201:enzymology / Q000473:pathology*; D009206:Myocardium / Q000201:enzymology / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D051381:Rats; D011917:Rats, Inbred Lew
C106876:5,5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulfonyl)phenyl-2(5H)-furanone; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D005663:Furans; D007527:Isoenzymes; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D001241:Aspirin