Anti-ischemic effects of nimesulide, a cyclooxygenase-2 inhibitor on the ischemic model of rabbit induced by isoproterenol.
The objective was to devise an animal model of myocardial infarction (MI) against which cardioprotective drugs might be tested. We describe the effects of nimesulide, a COX experience with development and validation of such a model. The rabbit was chosen in preference to rodents because its heart and cardiac circulation more closely resemble those of human. Thus, the cardiovascular system of anaesthetized male rabbits, 1 to 1.5 kg (n=11), was stressed by a single bolus intravenous injection of isoprenaline (ISP), 65 mg/kg. The effects of the injection were followed for sixteen days and were evaluated in four ways: 1) measurements of creatinine kinase isozyme and troponin-I (TPI) in serum 2) Electrocardiographic (ECG) changes (ST elevation and Q wave development) 3) Cardiac histopathology observed in tissue sections of the isolated of the heart. The histopathological analysis showed that rabbit heart on 2nd day after ISP injection showed changes of coagulation necrosis. Day 4 total coagulation with the loss of nuclear and striation associated with heavy interstitial infiltrate of neutrophils was found. Day 8 after infarction showed collagen deposition with capillary channels in between the remaining islands of myocytes in the infarcted area. On the 16th day scarring was complete. Coronary perfusion rates (CPR) and heart rate (HR) of the infarcted and nimesulide (a COX-2 inhibitor) treated rabbits displayed significant improvement (n=11) on each corresponding day after infarction as compared to the infarcted and saline treated rabbits (P<0.05). All four indices revealed similarities with effects commonly associated with MI in humans.
Saeed
Sheikh Arshad
SA
Dr Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical Sciences, University of Karachi, Pakistan. arshad.saeed@iccs.edu
Ahmed
Sagheer
S
D000318:Adrenergic beta-Agonists; D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects; D003402:Creatine Kinase / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000627:therapeutic use*; D004562:Electrocardiography / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D007511:Ischemia / Q000139:chemically induced* / Q000188:drug therapy* / Q000201:enzymology; D007545:Isoproterenol; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy / Q000473:pathology; D009206:Myocardium / Q000201:enzymology / Q000473:pathology; D009336:Necrosis; D011817:Rabbits; D013449:Sulfonamides / Q000627:therapeutic use*; D019210:Troponin I / Q000378:metabolism
D000318:Adrenergic beta-Agonists; D052246:Cyclooxygenase 2 Inhibitors; D013449:Sulfonamides; D019210:Troponin I; D003402:Creatine Kinase; D007545:Isoproterenol; C012655:nimesulide