Aspirin before reperfusion blunts the infarct size limiting effect of atorvastatin

Yochai Birnbaum, Yu Lin, Yumei Ye, Juan D. Martinez, Ming He Huang, Charles Y. Lui, Jose R. Perez-Polo, Barry F. Uretsky

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

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 PGI2 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 group), 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.

Original languageEnglish (US)
Pages (from-to)H2891-H2897
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume292
Issue number6
DOIs
StatePublished - Jun 1 2007

Keywords

  • Acetylsalicylic acid
  • Cyclooxygenase-2

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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    Birnbaum, Y., Lin, Y., Ye, Y., Martinez, J. D., Huang, M. H., Lui, C. Y., Perez-Polo, J. R., & Uretsky, B. F. (2007). Aspirin before reperfusion blunts the infarct size limiting effect of atorvastatin. American Journal of Physiology - Heart and Circulatory Physiology, 292(6), H2891-H2897. https://doi.org/10.1152/ajpheart.01269.2006