Chronic Pretreatment With Celecoxib Reduces Infarct SizeLada-Moldovan, Laura BSc; Kaloustian, Sévan MSc; Bah, Thierno Madjou MSc; Girard, Stéphanie-Anne BSc; Déry, Marc-André BSc; Rousseau, Guy PhDJournal of Cardiovascular Pharmacology: July 2009 - Volume 54 - Issue 1 - p 31-37 doi: 10.1097/FJC.0b013e3181aa3905 Original Article Buy Abstract Author InformationAuthors Article MetricsMetrics 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. From the Centre de recherche, Hôpital du Sacré-Cœur de Montréal and Department of Pharmacology, Université de Montréal, Montreal, Quebec, Canada. Received for publication January 8, 2009; accepted April 15, 2009. The authors report no conflicts of interest. Reprints: Guy Rousseau, PhD, Centre Biomédecine, Hôpital du Sacré-Cœur de Montréal 5400, boul. Gouin ouest, Montreal (Québec), Canada H4J 1C5 (e-mail: Guy.Rousseau@umontreal.ca). © 2009 Lippincott Williams & Wilkins, Inc.