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

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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)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume292
Issue number6
DOIs
StatePublished - Jun 2007

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Aspirin
Reperfusion
Coronary Occlusion
Coronary Vessels
Atorvastatin Calcium
Up-Regulation
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Epoprostenol
Acute Coronary Syndrome
Sprague Dawley Rats
Coloring Agents
Water

Keywords

  • Acetylsalicylic acid
  • Cyclooxygenase-2

ASJC Scopus subject areas

  • Physiology

Cite this

Aspirin before reperfusion blunts the infarct size limiting effect of atorvastatin. / Birnbaum, Yochai; Lin, Yu; Ye, Yumei; Martinez, Juan D.; Huang, Ming He; Lui, Charles Y.; Perez-Polo, Jose R.; Uretsky, Barry F.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 292, No. 6, 06.2007.

Research output: Contribution to journalArticle

Birnbaum, Yochai ; Lin, Yu ; Ye, Yumei ; Martinez, Juan D. ; Huang, Ming He ; Lui, Charles Y. ; Perez-Polo, Jose R. ; Uretsky, Barry F. / Aspirin before reperfusion blunts the infarct size limiting effect of atorvastatin. In: American Journal of Physiology - Heart and Circulatory Physiology. 2007 ; Vol. 292, No. 6.
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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.",
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N2 - 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.

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