Effect of Pravastatin on Left Ventr icular Remodeling in CS866-treated Rats with Myocardial Infarction
Date Issued
2003-07-31
Date
2003-07-31
Author(s)
蔡長和
DOI
912314B002227
Abstract
Background— Reactive cardiomyocyte hypertrophy after myocardial infarction is an
important risk factor for arrhythmias. Both angiotensin receptor antagonists
and 3-hydroxy-3-methylgultaryl coenzyme A (HMG-CoA) reductase
inhibitors have been shown to decrease cardiovascular morbidity and mortality.
Whether combination treatment may be superior to either drug alone on
cardiomyocyte hypertrophy remains unclear.
Methods and Results— After ligation of the left anterior descending artery, rats were
randomized to both, 1, or neither of the angiotensin receptor antagonist Cs866
(0.01, 0.1, 1, and 2 mg/kg per day) and HMG-CoA reductase inhibitor
pravastatin (5 mg/kg/day) for four weeks. Each drug, when given alone,
decreased cardiomyocyte sizes isolated by enzymatic dissociation at the
border zone compared with vehicles. However, compared with either drug
alone, combined Cs866 and pravastatin prevent cardiomyocyte hypertrophy to
a larger extent. The myocardial endothelin-1 levels at the border zone were
6.5-fold higher (P <0.0001) in the vehicle group compared with the sham
group, which can be inhibited after pravastatin administration. Further
evaluation of combination therapy with a low dose of Cs866 (0.01 mg/kg/day)
significantly prevented cardiomyocyte hypertrophy compared with pravastatin
alone (3020 ± 368 vs. 3202 ± 406 mm2 in the pravastatin-treated group, P =
0.04). With the highest dose of Cs866 (2 mg/kg/day) in combined therapy, we
observed a further reduction of cardiomyocyte hypertrophy although tissue
endothelin-1 levels remained stable in combination groups. Measurements of
arrhythmic score mirrored those of cardiomyocyte hypertrophy.
Conclusions— Dual-therapy with pravastatin and Cs866, which produced an additive
reduction in cardiomyocyte hypertrophy in a dose-dependent manner after
myocardial infarction through different mechanisms, decreases the propensity
of the heart to arrhythmogenesis. Because cotreatment with statins and
Cs866 acts in an additive manner, these observations provide important
therapeutic implications in pharmacotherapy of clinical practice.
Subjects
Arrhythmias
Hypertrophy
Myocardial infarction
Myocytes
Publisher
臺北市：國立臺灣大學醫學院外科
Type
report
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