Aspirin before reperfusion blunts the infarct size limiting effect of atorvastatin

We assessed whether aspirin (acetylsalicylic acid. ASA). administered before reperfusion. abrogates the infarct size (IS)limiting effect of atorvastatin (ATV). Statins reduce IS. This dose-dependent effect is mediated by upregulation of cycloxygenase-2 (COX2) and PGI(2) production. Administration of selective COX2-inhibitors either with ATV for 3 days or immediately before coronary Occlusion blocks the IS-limiting effect of ATV. Sprague-Dawley rats received 3-day ATV (10 mg (.) kg(-1) (.) day(-1)) or water alone. Rats underwent 30 min coronary artery occlusion and 4 h reperfusion (IS Protocol. n = 8 in each croup). or rats underwent 30 min coronary artery Occlusion and 10 min reperfusion (enzyme expression and activity protocol. n = 4 in each group). Immediately before reperfusion rats received intravenous ASA (5. 10. or 20 mg/kg) or saline. Area-at-risk (AR) was assessed by blue dye and IS by triphenyltetrazolium chloride. ATV reduced IS (10.1 +/- 1.4% of the AR) compared with controls (31.0 +/- 2.2%). Intravenous ASA alone did not affect IS (29.0 +/- 2.6%); however, ASA dose dependently (5. 10. and 20 mg/kg) attenuated the protective effect of ATV on IS (15.8 +/- 0.9%, 22.0 +/- 1.6%, and 23.7 +/- 3.8%. respectively). ASA dose dependently blocked the upregulation of COX2 by ATV. COX2 activity was as follows: control, 8.93 +/- 0.90 pg/mg: ATV. 75.85 +/- 1.08 pg/mg: ATV + ASA5, 34.39 +/- 1.48 pg/mg; ATV + ASA10. 19.87 +/- 1.10 pg/mg; and ATV + ASA20, 9.36 +/- 0.94 pg/mg. ASA. administered before reperfusion in doses comparable to those used in the clinical setting. abrogates the IS-limiting effect of ATV in a model with mechanical Occlusion Of the coronary artery. This potential adverse interaction should be further investigated in the clinical setting of acute coronary syndromes.