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CLINICAL STUDY

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

^* Experimental Research Laboratory, Division of Cardiology, University of Louisville, and the Jewish Hospital Heart and Lung Institute, Louisville, Kentucky, USA

Manuscript received August 14, 2002; revised manuscript received November 8, 2002, accepted November 22, 2002.

^* Reprint requests and correspondence: Dr. Roberto Bolli, Division of Cardiology, University of Louisville, Louisville, Kentucky 40292, USA.
rbolli{at}louisville.edu

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.

Abbreviations and Acronyms   ASA = acetylsalicylic acid (aspirin)   COX = cyclooxygenase   NSAID(s) = nonsteroidal anti-inflammatory drug(s)   PC = preconditioning   PG = prostaglandin   WTh = systolic wall thickening

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