Effects of Rosuvastatin and Pitavastatin on Ischemia-Induced Myocardial Stunning in Dogs

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 fur...

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Main Authors: Kumi Satoh, Akira Takaguri, Mai Itagaki, Seiichiro Kano, Kazuo Ichihara
Format: Article
Language:English
Published: Elsevier 2008-01-01
Series:Journal of Pharmacological Sciences
Online Access:http://www.sciencedirect.com/science/article/pii/S1347861319314793
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spelling doaj-a8646e886d044e688f37584bbe7f73f52020-11-24T22:01:17ZengElsevierJournal of Pharmacological Sciences1347-86132008-01-011064593599Effects of Rosuvastatin and Pitavastatin on Ischemia-Induced Myocardial Stunning in DogsKumi Satoh0Akira Takaguri1Mai Itagaki2Seiichiro Kano3Kazuo Ichihara4Division of Pharmacology, Hokkaido Pharmaceutical University, 7-1 Katsuraoka, Otaru 047-0264, JapanDivision of Pharmacology, Hokkaido Pharmaceutical University, 7-1 Katsuraoka, Otaru 047-0264, JapanDivision of Pharmacology, Hokkaido Pharmaceutical University, 7-1 Katsuraoka, Otaru 047-0264, JapanDivision of Pharmacology, Hokkaido Pharmaceutical University, 7-1 Katsuraoka, Otaru 047-0264, JapanDivision of Pharmacology, Hokkaido Pharmaceutical University, 7-1 Katsuraoka, Otaru 047-0264, Japan; Corresponding author. ichihara1@hokuyakudai.ac.jpIncomplete 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 10−6M and higher, whereas rosuvastatin and pravastatin up to 10−5M 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. Keywords:: 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, heart, coronary artery, ischemia, ATPhttp://www.sciencedirect.com/science/article/pii/S1347861319314793
collection DOAJ
language English
format Article
sources DOAJ
author Kumi Satoh
Akira Takaguri
Mai Itagaki
Seiichiro Kano
Kazuo Ichihara
spellingShingle Kumi Satoh
Akira Takaguri
Mai Itagaki
Seiichiro Kano
Kazuo Ichihara
Effects of Rosuvastatin and Pitavastatin on Ischemia-Induced Myocardial Stunning in Dogs
Journal of Pharmacological Sciences
author_facet Kumi Satoh
Akira Takaguri
Mai Itagaki
Seiichiro Kano
Kazuo Ichihara
author_sort Kumi Satoh
title Effects of Rosuvastatin and Pitavastatin on Ischemia-Induced Myocardial Stunning in Dogs
title_short Effects of Rosuvastatin and Pitavastatin on Ischemia-Induced Myocardial Stunning in Dogs
title_full Effects of Rosuvastatin and Pitavastatin on Ischemia-Induced Myocardial Stunning in Dogs
title_fullStr Effects of Rosuvastatin and Pitavastatin on Ischemia-Induced Myocardial Stunning in Dogs
title_full_unstemmed Effects of Rosuvastatin and Pitavastatin on Ischemia-Induced Myocardial Stunning in Dogs
title_sort effects of rosuvastatin and pitavastatin on ischemia-induced myocardial stunning in dogs
publisher Elsevier
series Journal of Pharmacological Sciences
issn 1347-8613
publishDate 2008-01-01
description 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 10−6M and higher, whereas rosuvastatin and pravastatin up to 10−5M 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. Keywords:: 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, heart, coronary artery, ischemia, ATP
url http://www.sciencedirect.com/science/article/pii/S1347861319314793
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