Reduction of infarct size by short-term pretreatment with atorvastatin

Yochai Birnbaum, Taras Ashitkov, Barry F. Uretsky, Scott Ballinger, Massoud Motamedi

Research output: Contribution to journalArticle

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Abstract

Previous studies have suggested that the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors attenuate ischemia-reperfusion injury by increasing the activity of endothelial nitric oxide synthase (eNOS). We assessed whether short-term treatment with atorvastatin reduces myocardial infarct size in the rat. Rats (male Sprague-Dawley) received atorvastatin 2 mg/kg per day (n=9), 10 mg/kg per day (n=8), or 75 mg/kg per day (n=11), or placebo (n=11) by gastric gavage for 3 days. Two additional groups received atorvastatin 10 mg/kg (n=7) or placebo (n=7) for 3 days and the nonselective nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), 15 mg/kg intravenously 15 min before surgery. All rats underwent 30 min of coronary artery occlusion followed by 180 min of reperfusion. Ischemic myocardium at risk was assessed with blue dye and infarct size by triphenyltetrazolium chloride. Ischemic myocardium at risk was comparable among groups. Infarct size, expressed as a percentage of the myocardium at risk, was significantly smaller in the atorvastatin 75 mg/kg group (22.6±2.8%; p =0.035 vs. placebo) and atorvastatin 10 mg/kg (20.3±3.8%; p=0.022 vs. placebo) compared with placebo (37.5±4.3%). The effect of atorvastatin 2 mg/kg was of smaller magnitude and did not reach statistical significance (infarct size 30.6±4.2% of the myocardium at risk). L-NAME abolished the protective effect of atorvastatin 10 mg/kg per day. Infarct size was 43.0±4.1% in the atorvastatin group and 39.4±3.3% in the placebo group (p=0.503). In conclusion, short-term (3 days) atorvastatin (10-75 mg/kg/d) significantly reduced myocardial infarct size. The protective effect was completely abolished by L-NAME, strongly suggesting that this protective effect is mediated via the nitric oxide synthase pathway.

Original languageEnglish (US)
Pages (from-to)25-30
Number of pages6
JournalCardiovascular Drugs and Therapy
Volume17
Issue number1
DOIs
StatePublished - 2003

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NG-Nitroarginine Methyl Ester
Placebos
Myocardium
Nitric Oxide Synthase
Myocardial Infarction
Atorvastatin Calcium
Nitric Oxide Synthase Type III
Coronary Occlusion
Reperfusion Injury
Reperfusion
Sprague Dawley Rats
Coronary Vessels
Stomach
Oxidoreductases
Coloring Agents
Therapeutics

Keywords

  • 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors
  • Infarct size
  • Myocardial infarction
  • Nitric oxide
  • Rat
  • Statins

ASJC Scopus subject areas

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

Cite this

Reduction of infarct size by short-term pretreatment with atorvastatin. / Birnbaum, Yochai; Ashitkov, Taras; Uretsky, Barry F.; Ballinger, Scott; Motamedi, Massoud.

In: Cardiovascular Drugs and Therapy, Vol. 17, No. 1, 2003, p. 25-30.

Research output: Contribution to journalArticle

Birnbaum, Yochai ; Ashitkov, Taras ; Uretsky, Barry F. ; Ballinger, Scott ; Motamedi, Massoud. / Reduction of infarct size by short-term pretreatment with atorvastatin. In: Cardiovascular Drugs and Therapy. 2003 ; Vol. 17, No. 1. pp. 25-30.
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