Evidence of Prothrombotic Effect of Celecoxib and Risk of Myocardial Infarction

The present work was devoted to study the effects of celecoxib, a selective COX-2 inhibitor, on the risk of myocardial infarction (MI) induced experimentally in rats by subcutaneous injection of isoprenaline. The effects of celecoxib were compared with those of ibuprofen, the non-selective COX inhibitor. Sixty rats were used and divided into six groups, each of 10 rats. The groups received either saline (control group, group I), isoprenaline alone (group II), isoprenaline and celecoxib (group III), isoprenaline and ibuprofen (group IV), celecoxib alone (group V), or ibuprofen alone (group VI), for two weeks. Acute MI was induced in groups II, lIT, and IV of rats, by subcutaneous injection of isoprenaline (50 mg/kg/day) for two successive days. At the end of the study, all rats were subjected to ECG recording; measurement of serum levels of cardiac injury biomarkers total creatine kinase (CK) and subtype B (CK-MB); assessment of ex-vivo platelet aggregation in response to ADP, collagen, and arachidonic acid; and histopathological examination of the isolated hearts. The results obtained revealed that induction of acute MI by isoprenaline resulted in significant ECG changes and marked rise in the levels of MI biomarkers, together with histological evidence of myocardial damage. These changes were associated with significant increase in platelet aggregation. Treatment with celecoxib leads to exaggeration of the MI manifestations induced by isoprenaline, with more marked changes in the ECG. selUm MI markers, enhanced platelet aggregation, and significant increase in the area of cardiac infarction. On the contrary, treatment with ibuprofen produces no significant changes in the MImanifestations induced by isoprenaline, with similar percentage of infarct surface area. It is concluded that selective COX-2 inhibitor, celecoxib can exaggerate myocardial damage and increase infarction size. The current data would suggest that the use of selective COX-2 inhibitors, might lead to increased risk for thrombotic cardiovascular events probably via prothrombotic effect with enhanced platelet reactivity.