Circulation. 2001;104:982-985
doi: 10.1161/hc3401.095946
doi: 10.1161/hc3401.095946
(Circulation. 2001;104:982.)
© 2001 American Heart Association, Inc.
Brief Rapid Communications |
Improvement of Left Ventricular Remodeling and Function by Hydroxymethylglutaryl Coenzyme A Reductase Inhibition With Cerivastatin in Rats With Heart Failure After Myocardial Infarction
From the Medizinische Klinik der Julius-Maximilians-Universität Würzburg (J.B., P.G., D.F., G.E.), and the Klinik für Innere Medizin-Kardiologie (M.C.), Philipps-Universität Marburg, Germany.
Correspondence to Dr Johann Bauersachs, Medizinische Universitätsklinik, Josef-Schneider-Str 2, D-97080 Würzburg, Germany. E-mail j.bauersachs{at}uni-wuerzburg.de
Background— Hydroxymethylglutaryl coenzyme A reductase inhibitors (statins) attenuate angiotensin II-induced cellular signaling. Because angiotensin II is involved in left ventricular (LV) remodeling after myocardial infarction (MI), we examined the effects of statin treatment in an experimental model of chronic heart failure after MI.
Methods and Results— Rats with extensive MI were treated with placebo or cerivastatin (0.3 mg/kg per day) as a dietary supplement or via gavage for 11 weeks starting on the 7th postoperative day. Infarct size and cholesterol levels were similar among all groups. LV cavity area, an index of LV dilatation, was reduced in MI rats on cerivastatin compared with placebo. LV end-diastolic pressure was increased in MI rats on placebo (24.1±4.1 mm Hg versus sham: 5.1±0.3 mm Hg; P<0.01), and it was significantly reduced by cerivastatin treatment (13.7±2.7 mm Hg; P<0.05 versus placebo). Cerivastatin partially normalized LV dP/dtmax and dP/dtmin, indices of LV systolic and diastolic function, which were significantly reduced in MI rats on placebo. Improvement of LV function by cerivastatin was accompanied by a reduced expression of collagen type I and ß-myosin heavy chain. LV endothelial nitric oxide synthase was increased, whereas the nitrotyrosine protein level was decreased in MI rats by cerivastatin treatment.
Conclusions— Cerivastatin improved LV remodeling and function in rats with heart failure. This effect was associated with an attenuated LV expression of fetal myosin heavy chain isoenzymes and collagen I. Statin treatment may retard the progression of chronic heart failure.
Key Words: myocardial infarction • heart failure • myocardium • remodeling • nitric oxide synthase
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
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