Naproxen and Diclofenac Attenuate Atorvastatin-induced Preconditioning of the Myocardium

Statins reduce infarct size (IS) in ischemia-reperfusion injury of the myocardium. Inhibition of cyclooxygenase-2 (COX-2) attenuates this benefit. We investigated the effect of two widely used non-selective non-steroidal anti-inflammatory drugs (NSAIDs) with different degree of anti-COX-2 activity on atorvastatin-mediated preconditioning. Wistar rats received oral atorvastatin (10 mg∙kg-1∙day-1), naproxen (10 mg∙kg-1∙day-1), diclofenac (8 mg∙kg-1∙day-1), atorvastatin+naproxen, atorvastatin+diclofenac or water for three days. Hearts were then excised and perfused in the Langendorff system. Area at risk (AR) and IS were determined after 30 min of regional ischemia and 120 min of reperfusion. Atorvastatin reduced IS by 51.3% compared with controls (14.7 ± 3.9% vs. 30.2 ± 4.6% of the AR; P < 0.001). Naproxen and diclofenac alone did not alter IS compared to control. Diclofenac completely abrogated atorvastatin-mediated protection of the myocardium. Naproxen significantly attenuated but did not eliminate the IS reducing the effect of atorvastatin when compared with controls (P = 0.038). The difference in IS between the atorvastatin+naproxen group and the atorvastatin+diclofenac group showed a strong trend in reaching statistical significance (P = 0.058), but was not found to be significant. Our results suggest relatively small, but noticeable differences among non-selective NSAIDs in their potential to attenuate statin-mediated preconditioning.