Journal of Pharmacological Sciences
Online ISSN : 1347-8648
Print ISSN : 1347-8613
ISSN-L : 1347-8613
Full Papers
Effects of Rosuvastatin and Pitavastatin on Ischemia-Induced Myocardial Stunning in Dogs
Kumi SatohAkira TakaguriMai ItagakiSeiichiro KanoKazuo Ichihara
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JOURNAL FREE ACCESS

2008 Volume 106 Issue 4 Pages 593-599

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Abstract

Incomplete recovery of myocardial contraction after reperfusion following brief ischemia is called the “stunning phenomenon” in an animal experiment. A hydrophilic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor (statin) does not affect this phenomenon, but lipophilic statins further reduce the contraction during reperfusion. The effects of novel hydrophilic rosuvastatin and lipophilic pitavastatin on myocardial stunning in dogs were examined. In a preliminary experiment in vitro, pitavastatin reduced L6 cell viability at 106 M and higher, whereas rosuvastatin and pravastatin up to 105 M did not show such effects. An empty capsule or a capsule filled with rosuvastatin (2 mg/kg per day) or pitavastatin (0.4 mg/kg per day) was orally administered to dogs. After 3 weeks, both statins lowered the serum cholesterol level to the same extent. Under pentobarbital anesthesia, dogs were subjected to 15-min ischemia followed by 120-min reperfusion. Ischemia arrested the myocardial contraction in the ischemic area, and reperfusion recovered it but incompletely, showing the stunning phenomenon. Rosuvastatin did not modify the stunning phenomenon, while pitavastatin further deteriorated the myocardial contraction during reperfusion.

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© The Japanese Pharmacological Society 2008
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