Pretreatment with high-dose statin, but not low-dose statin, ezetimibe, or the combination of low-dose statin and ezetimibe, limits infarct size in the rat

Yochai Birnbaum, Yu Lin, Yumei Ye, Ramanna Merla, Jose R. Perez-Polo, Barry F. Uretsky

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

Statins reduce infarct size by upregulating nitric oxide synthases and PGI2 production. In this article, the infarct size-limiting effect of low-dose simvastatin + ezetimibe, ezetimibe, and high-dose statins were compared. Rats received 3-day water, atorvastatin (10 mg/kg/d), simvastatin (10 mg/kg/d), simvastatin (2 mg/kg/d), simvastatin (2 mg/kg/d) + ezetimibe (1 mg/kg/d), or ezetimibe. Rats underwent 30-minute coronary artery occlusion and 4-hour reperfusion. Atorvastatin and simvastatin 10 reduced infarct size, whereas simvastatin 2, ezetimibe, and simvastatin 2 + ezetimibe had no effect. Atorvastatin and simvastatin 10 increased nitric oxide synthases activity, whereas simvastatin-2, ezetimibe, and simvastatin-2 + ezetimibe had only a small effect. Atorvastatin and simvastatin 10 significantly increased myocardial 6-ketoprostaglandin F levels, whereas simvastatin 2, ezetimibe, and simvastatin 2 + ezetimibe had no effect. High-dose statin is required to decrease infarct size, upregulate myocardial nitric oxide synthases activities, and increase 6-keto prostaglandin F levels. Combination of ezetimibe and low-dose statin is ineffective in modulating myocardial biochemical changes associated with cardioprotection.

Original languageEnglish (US)
Pages (from-to)72-79
Number of pages8
JournalJournal of Cardiovascular Pharmacology and Therapeutics
Volume13
Issue number1
DOIs
StatePublished - Mar 1 2008

Keywords

  • Ezetimibe
  • Infarct size
  • Nitric oxide synthase
  • Prostacyclin
  • Statins

ASJC Scopus subject areas

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

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