羟甲基戊二酰辅酶A还原酶抑制对心肌梗死后左心室重构的影响：一项实验性系列心脏磁共振成像研究

Impact of hydroxymethylglutaryl coenzyme a reductase inhibition on left ventricular remodeling after myocardial infarction: an experimental serial cardiac magnetic resonance imaging study.

作者信息

Nahrendorf Matthias, Hu Kai, Hiller Karl-Heinz, Galuppo Paolo, Fraccarollo Daniela, Schweizer German, Haase Axel, Ertl Georg, Bauer Wolfgang R, Bauersachs Johann

机构信息

Medizinische Universitätsklinik, University of Würzburg, Josef Schneider-Strasse 2, 97080 Würzburg, Germany.

出版信息

J Am Coll Cardiol. 2002 Nov 6;40(9):1695-700. doi: 10.1016/s0735-1097(02)02375-6.

DOI:10.1016/s0735-1097(02)02375-6

PMID:12427425

Abstract

OBJECTIVES

We sought to assess the influence of long-term hydroxymethylglutaryl coenzyme A reductase inhibition (statin) therapy on left ventricular (LV) remodeling after myocardial infarction (MI) by use of serial cardiac magnetic resonance imaging (CMRI) studies.

BACKGROUND

Statin therapy has been shown to reduce cardiac hypertrophy in vitro and in vivo, but the influence on LV post-MI remodeling is largely unknown.

METHODS

The CMRI measurements were taken four and 12 weeks after left coronary artery ligation in a 7.05-tesla Biospec. The MI size, LV mass and volumes, cardiac output (CO), and ejection fraction were determined. Rats were treated for 12 weeks with either placebo (P), cerivastatin (C; 0.6 mg/kg body weight per day) as a dietary supplement, or cerivastatin plus the nitric oxide synthase (NOS) inhibitor N-methyl-L-arginine methyl ester (L-NAME, 76 mg/100 ml) and hydralazine (8 mg/100 ml) in drinking water (CLH) to assess the contribution of endogenous nitric oxide formation.

RESULTS

Administration of cerivastatin attenuated hypertrophy after MI, and this effect was completely abolished by NOS inhibition (increase of LV mass from 4 to 12 weeks after MI: 235.3 +/- 33.7 mg with P vs. 59.8 +/- 20.5 mg with C vs. 239.5 +/- 16.0 mg with CLH; p < 0.05 vs. P and CLH). Left ventricular dilation was not changed (increase of end-diastolic volume from 4 to 12 weeks after MI: 108.7 +/- 28.8 with P vs. 126.6 +/- 20.5 with C vs. 173.7 +/- 25.1 with CLH; p = NS). The CO was higher in the cerivastatin group (12 weeks: 76.1 +/- 2.9 ml/min with P vs. 95.8 +/- 4.8 ml/min with C; p < 0.05). The effects of cerivastatin were abolished by NOS inhibition in the CLH group (CO at 12 weeks: 69.3 +/- 2.8 ml/min, p < 0.05 vs. C).

CONCLUSIONS

Left ventricular remodeling was profoundly changed by statin treatment. Hypertrophy was attenuated, and global function was improved. These positive effects were abolished by NOS inhibition.

摘要

目的

我们试图通过系列心脏磁共振成像（CMRI）研究，评估长期羟甲基戊二酰辅酶A还原酶抑制（他汀类）疗法对心肌梗死（MI）后左心室（LV）重构的影响。

背景

他汀类疗法已被证明在体外和体内均可减轻心脏肥大，但对MI后LV重构的影响很大程度上尚不清楚。

方法

在7.05特斯拉的Biospec中，于左冠状动脉结扎后4周和12周进行CMRI测量。测定MI大小、LV质量和容积、心输出量（CO）以及射血分数。大鼠接受为期12周的治疗，分别给予安慰剂（P）、作为饮食补充剂的西立伐他汀（C；0.6毫克/千克体重/天），或在饮用水中给予西立伐他汀加一氧化氮合酶（NOS）抑制剂N-甲基-L-精氨酸甲酯（L-NAME，76毫克/100毫升）和肼屈嗪（8毫克/100毫升）（CLH），以评估内源性一氧化氮生成的作用。

结果

给予西立伐他汀可减轻MI后的肥大，而NOS抑制可完全消除这种作用（MI后4至12周LV质量增加：P组为235.3±33.7毫克，C组为59.8±20.5毫克，CLH组为239.5±16.0毫克；与P组和CLH组相比，p<0.05）。左心室扩张未发生变化（MI后4至12周舒张末期容积增加：P组为108.7±28.8，C组为126.6±20.5, CLH组为173.7±25.1；p=无显著性差异）。西立伐他汀组的CO较高（12周时：P组为76.1±2.9毫升/分钟，C组为95.8±4.8毫升/分钟；p<0.05）。CLH组中NOS抑制消除了西立伐他汀的作用（12周时CO：69.3±2.8毫升/分钟，与C组相比，p < 0.05）。