Chronic pretreatment with celecoxib reduces infarct size.
This study was designed to evaluate the effect of long-term pretreatment with celecoxib, a cyclooxygenase-2 inhibitor, on myocardial infarct size. Celecoxib (3 mg/kg/day i.p; n = 16) or vehicle (DMSO 50%; EtOH 15%; distilled water, n = 16) was administered chronically to male Sprague-Dawley rats through ALZET osmotic pumps for 28 days. Under anaesthesia, the animals were then subjected to left anterior descending coronary artery occlusion for 40 minutes, followed by 24-hour reperfusion. The results show that myocardial infarct size in celecoxib-treated rats was significantly reduced compared to the control group (37.5 +/- 2.5% versus 48.0 +/- 2.6% of the area at risk, P < 0.05, n = 10 per group). Accumulation of neutrophils, estimated by myeloperoxidase levels, indicated an increase in the ischemic area without any significant difference between groups. No significant difference was observed between the treated and vehicle groups in terms of plasma prostaglandin E2 and tumour necrosis factor-alpha. Apoptosis, evaluated by Bax/Bcl-2 and terminal dUTP nick-end labelled-positive cells, was significantly decreased in the subendocardial layer of the ischemic area in celecoxib-treated rats. This study indicates that pretreatment with celecoxib can reduce infarct size by a mechanism, which may involve apoptosis inhibition.
Lada-Moldovan
Laura
L
Centre de recherche, Hôpital du Sacré-Coeur de Montréal and Department of Pharmacology, Université de Montréal, Montreal, Quebec, Canada H4J 1C5.
Kaloustian
Sévan
S
Bah
Thierno Madjou
TM
Girard
Stéphanie-Anne
SA
Déry
Marc-André
MA
Rousseau
Guy
G
D000818:Animals; D000068579:Celecoxib; D052246:Cyclooxygenase 2 Inhibitors / Q000627:therapeutic use*; D004195:Disease Models, Animal; D007263:Infusions, Parenteral; D007511:Ischemia / Q000473:pathology*; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology*; D015428:Myocardial Reperfusion Injury / Q000473:pathology*; D011720:Pyrazoles / Q000627:therapeutic use*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013449:Sulfonamides / Q000627:therapeutic use*
D052246:Cyclooxygenase 2 Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D000068579:Celecoxib