Browse > Article

Anti-ischemic Effects of Nimesulide, a Cyclooxygenase-2 Inhibitor on the Ischemic Model of Rabbit Induced by Isoproterenol  

Saeed, Sheikh Arshad (Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical Sciences, University of Karachi)
Ahmed, Sagheer (Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical Sciences, University of Karachi)
Publication Information
Archives of Pharmacal Research / v.29, no.11, 2006 , pp. 977-983 More about this Journal
Abstract
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.
Keywords
Isoprenaline (ISP); Troponin I (TPI); Creatine Phosphokinase (CPK); Electrocardiography (ECG); Histopathology; Coronary perfusion rates (CPR);
Citations & Related Records

Times Cited By Web Of Science : 3  (Related Records In Web of Science)
Times Cited By SCOPUS : 2
연도 인용수 순위
1 Adams, J. E. 3rd., Bodor, G. S., Davila-Roman, V.G., Delmez, J. A., Apple, F. S., Ladenson, J. H., and Jaffe, A. S., Cardiac troponin I: a marker with high specificity for cardiac injury. Circulation, 88, 101-106 (1993)   DOI   ScienceOn
2 Baker, C. S., Hall, R. J., Evans, T. J., Pomerance, A., Maclouf, J., Creminon, C., Yacoub, M. H., and Polak, J.M., Cyclooxygenase- 2 is widely expressed in atherosclerotic lesions affecting native and transplanted human coronary arteries and colocalized with inducible nitric oxide synthase and nitrotyrosine particularly in macrophages. Arterioscler. Thromb. Vasc. Biol., 19, 646-655 (1999)   DOI   ScienceOn
3 Koenig, W., Inflammation and coronary heart disease: an overview. Caridol. Rev., 9, 31-35 (2001)   DOI   ScienceOn
4 Langendorff. Pfluners Arch. Ges. Physiol., 190, 280 (1985)
5 Mobert, J. and Becker, B. F., Cyclooxygenase inhibition aggravates ischaemia-reperfusion injury in the perfused guinea pig heart: involvement of isoprostanes. J. Am. Coll. Cardiol., 31, 1687-1694 (1998)   DOI   ScienceOn
6 Silverstein, F. E., Faich, G., Goldstein, J. L., Simon, L. S., Pincus, T., Whelton, A., Makuch, R., Eisen, G., Agrawal, N. M., Stenson, W. F., Burr, A. M., Zhao, W. W., Kent, J. D., Lefkowith, J. B., Verburg, K. M., and Geis, G. S., Gastrointestinal toxicity with celecoxib vs nonsterodial anti-inflammatory drugs for osteoarthritis and rheumatoid arthritis: the CLASS Study. A randomized control trial. JAMA, 284, 1247- 1255 (2000)   DOI   ScienceOn
7 O'Banion M., Cyclooxygenase-2: Molecular biology, pharmacology and neurobiology. Critc. Rev. Neurobiol., 13, 45-82 (1999)   DOI
8 Saito, T., Rodger, I. W., Hu, F., Shennib, H., and Giaid, A., Inhibition of cyclooxygenase-2 improves cardiac function in myocardial infarction. Biochem. Biphys. Res. Commun., 273, 772-775 (2000)   DOI   ScienceOn
9 Schonbeck, U., Sukhova, G. K., Graber, P., Coulter, S., and Libby, P., Augmented expressoin of cyclooxygenase-2 in human atherosclerotic lesions. Am. J. Pathol., 155, 1281- 1291 (1999)   DOI   ScienceOn
10 Chenevard, R., Hurlimann, D., Bechir, M., Enseleit, F., Spieker, L., Hermann, M., Riesen, W., Gay, S., Gay, R. E., Neidhart, M., Michel, B., Luscher, T. F., Noll, G., and Ruschitzka, F., Selective COX-2 inhibition improves endothelial function in coronary artery disease. Circulation, 107, 405-409 (2003)   DOI   ScienceOn
11 Lecomte, M., Laneuville, O., Ji, C., DeWitt, D. L., and Smith, W. L., Acetylation of human prostaglandin endoperoxide synthase- 2 (cyclooxygenase-2) by aspirin. J. Biol. Chem., 269, 13207- 13215 (1994)
12 Bombardier, C., Laine, L., Reicin, A., Shapiro, D., Burgos- Vargas, R., Davis, B., Day, R., Ferraz, M. B., Hawkey, C. J., Hochberg, M. C., Kvien, T. K., and Schnitzer, T. J., Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis: VIGOR Study Group. N. Engl. J. Med., 243, 1520-1528 (2000)
13 Rosalki, S. B., An improved procedure for serum creatine phosphokinase determination. J. Lab. Clin. Med., 69, 696- 705 (1967)
14 Saeed, S. A., Atiq, M., Virani, S., and Gilani, A. H., New vistas in the therapeutic uses of aspirin. Res. Commun. Pharmacol. Toxicol., 6, 277-296 (2001)
15 Duffy, S. J., Castle, S. F., Harper, R. W. et al., Contribution of vasodilator prostanoids and nitric oxide to resting flow, metabolic vasodilatation, and flow-mediated dilation in human coronary circulation. Circulation, 100, 1951-1957 (1999)   DOI   ScienceOn
16 Heitzer, T., Just, H., and Munzel, T., Antioxidant vitamin C improves and endothelial dysfunction in chronic smokers. Circulation, 94, 6-9 (1996)   DOI   ScienceOn
17 Bonow, R. O., Lipson, L. C., Shaheen, F. H., Capurro, N. L., Inser, J. M., Roberst, W.C., Goldstein, R. E., and Epstein, S.E., Lack of effect of aspirin on myocardial infarct size in dogs. Am. J. Cardiol., 47, 258-264 (1981)   DOI   ScienceOn
18 Cai, H. and Harrison, D. G., Endothelial dysfunction in cardiovascular disease: the role of oxidant stress. Cirs. Res., 87, 840-844 (2000)   DOI   ScienceOn
19 Mukerjee, D., Nissen, S. E., and Topol, E. J., Risk of cardiovascular events associated with selective COX-2 inhibitors. JAMA. 286, 954-959 (2001)   DOI   ScienceOn
20 Saeed, S. A., Gilani, A. H., Sultan, B. H., Karim, R. M., and Shah, B. H., Myocardial ischemia and infarction in isoprenalinetreated rabbits: Role of cyclooxygenases. Bichem. Soc. Trans., 26, S342 (1998)   DOI
21 Belton, O., Byrne, D., Kearney, D., Leahy, A., and Fitzgerald, D. J., Cyclooxygenase-1 and -2 dependent prostacyclin formation in patients with atherosclerosis. Circulation, 102, 840- 845 (2000)   DOI   ScienceOn
22 Mukerjee, D., Selective Cyclooxygenase-2 (COX-2) inhibitors and potential risk of cardiovascular events. Biochem. Pharmacol., 63, 817-21 (2002)   DOI   ScienceOn