Effect of aspirin on late preconditioning against myocardial stunning in conscious rabbits

OBJECTIVES The goal of this study was to investigate the effect of three different doses of acetylsalicylic acid (aspirin) (ASA) on the late phase of ischemic preconditioning (PC) against myocardial stunning. BACKGROUND Although recent evidence indicates that the late phase of ischemic PC is mediated by cyclooxygenase-2 (COX-2), the effect of nonsteroidal anti-inflammatory drugs (NSAIDs) that inhibit COX-2 activity on late PC has not been evaluated; ASA is the most widely used NSAID. Therefore, we determined whether ASA impedes the development of late PC. METHODS Conscious rabbits underwent a protocol consisting of three days of six 4-min coronary occlusion/4-min reperfusion cycles. RESULTS Neither 5 mg/kg nor 10 mg/kg x 3 of ASA interfered with the protective effects of late PC against stunning. In contrast, the late PC effect was completely abrogated by 25 mg/kg of ASA. Low-dose (5 mg/kg) ASA effectively inhibited platelet aggregation but did not prevent the increase in COX-2 activity, whereas the highest dose (25 mg/kg) completely blocked COX-2 activity. CONCLUSIONS The administration of ASA either at antithrombotic doses (5 mg/kg), which are widely used to prevent cardiovascular events in patients, or at analgesic/antipyretic doses (10 mg/kg) does not interfere with the cardioprotective effects of late PC against myocardial stunning. In contrast, high doses of ASA (25 mg/kg), which are used as antirheumatic therapy, abrogate both COX-2 activity and late PC, suggesting that nonselective doses of NSAIDs should be used with caution in patients with atherosclerotic cardiovascular disease because they may deprive the heart of its innate defensive response.