Simvastatin preserves the ischemic-reperfused myocardium in normocholesterolemic rat hearts
Simvastatin preserves the ischemic-reperfused myocardium in normocholesterolemic rat hearts
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DOI：
10.1161/01.cir.100.2.178
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发表时间：
1999-07-13
期刊：
影响因子：
37.8
通讯作者：
Lefer, DJ
中科院分区：
文献类型：
--
作者：
Lefer, AM;Campbell, B;Lefer, DJ
背景-在多形核白细胞（PMN）存在的情况下，缺血再灌注会导致心脏收缩功能障碍以及心肌细胞损伤。这些有害作用在很大程度上是由于内皮功能障碍导致细胞粘附分子上调以及随后的中性粒细胞-内皮相互作用。在临床相关剂量下，辛伐他汀（一种 HMG-CoA 还原酶抑制剂）已被证明可以降低血清胆固醇水平并使内皮细胞功能正常化。我们想要在心肌缺血再灌注的对照模型中测试辛伐他汀对中性粒细胞介导的心脏功能障碍的影响。方法和结果-本研究检查了辛伐他汀在缺血（I）（20分钟）和再灌注（R）（45分钟）损伤的中性粒细胞依赖性离体灌注大鼠心脏模型中的作用。辛伐他汀25μg/大鼠的给药改善了冠状动脉血流并保留了左心室发展压(LVDP)和心脏收缩功能的dP/dt(max)指数。在灌注 PMN 和辛伐他汀的 I/R 心脏中，最终 LVDP 为 95+/-5 mm Hg，而在仅接受载体的 PMN 灌注 I/R 心脏中，最终 LVDP 为 49+/-4 mm Hg（P
Background-Ischemia followed by reperfusion in the presence of polymorphonuclear leukocytes (PMNs) results in cardiac contractile dysfunction as well as cardiomyocyte injury. These deleterious effects are due in large part to endothelial dysfunction leading to the upregulation of cell adhesion molecules and subsequent neutrophil-endothelium interaction. At clinically relevant doses, simvastatin, an HMG-CoA reductase inhibitor, has been shown to lower serum cholesterol levels and normalize endothelial cell function. We wanted to test the effects of simvastatin on neutrophil-mediated cardiac dysfunction in a controlled model of myocardial ischemia-reperfusion.Methods and Results-This study examines the effects of simvastatin in a neutrophil-dependent isolated perfused rat heart model of ischemia (I) (20 minutes) and reperfusion (R) (45 minutes) injury. Administration of simvastatin 25 mu g/rat improved coronary flow and preserved left ventricular developed pressure (LVDP) and dP/dt(max) indexes of cardiac contractile function. Final LVDP was 95+/-5 mm Hg in I/R hearts perfused with PMNs and simvastatin, compared with 49+/-4 mm Hg in PMN-perfused I/R hearts receiving only vehicle (P