Zheng Xia, Hu Shen-Jiang
Cardiovascular Department, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
Heart Vessels. 2006 Mar;21(2):116-23. doi: 10.1007/s00380-005-0868-y.
Simvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, has long been thought to exert its benefits by reducing cholesterol synthesis, and has been shown to significantly reduce cardiovascular events and mortality in patients with or without coronary artery disease. However, it is still unknown whether acute administration of simvastatin beneficially affects the cardiac function prior or during ischemia-reperfusion. The aim of this study is to evaluate the cardioprotective effect of acute simvastatin treatment on isolated rat hearts or isolated ischemia-reperfusion hearts. Hearts were isolated from male Sprague-Dawley rats and attached to a Langendorff apparatus. The isolated hearts with or without ischemia (15 min) and reperfusion (60 min) were perfused with different concentrations of simvastatin. The parameters of cardiac function (such as left ventricular developed pressure [LVDP], +dp/dt max, and -dp/dt max), heart rate, and coronary flow were recorded. Simvastatin (3-30 micromol/l) significantly increased LVDP, +dp/dt max, and -dp/dt max in isolated rat hearts perfused for 60 min. Heart rate was depressed by 30 micromol/l simvastatin and the coronary flow was increased by 10 and 30 micromol/l simvastatin. At a concentration of 100 micromol/l simvastatin, worsening of heart function and subsequent cardiac arrest occurred. Administration of simvastatin (3-30 micromol/l) significantly preserved cardiac function detected by LVDP, +dp/dt max, and -dp/dt max in the isolated ischemia/reperfused (15/60 min) rat hearts. Simvastatin also significantly decreased heart rate at 30 micromol/l, and increased coronary flow at 10 and 30 micromol/l in these rat hearts. However, the protective effect of simvastatin reverted to increased damage at 100 micromol/l. Only 3 micromol/l simvastatin pretreatment before 15/60 min ischemia-reperfusion altered LVDP, +dp/dt max, and -dp/dt max. Both heart rate and coronary flow were unaltered after simvastatin pretreatment. Since simvastatin at a concentration lower than 100 micromol/l exerted beneficial effects on cardiac function in isolated perfused rat hearts, it could be applied just after myocardial ischemia and reperfusion.
辛伐他汀是一种3-羟基-3-甲基戊二酰辅酶A（HMG-CoA）还原酶抑制剂，长期以来人们一直认为它通过降低胆固醇合成发挥有益作用，并且已证明它能显著降低有或无冠状动脉疾病患者的心血管事件和死亡率。然而，急性给予辛伐他汀是否在缺血再灌注之前或期间对心脏功能产生有益影响仍不清楚。本研究的目的是评估急性辛伐他汀治疗对离体大鼠心脏或离体缺血再灌注心脏的心脏保护作用。从雄性Sprague-Dawley大鼠分离心脏并连接到Langendorff装置。用不同浓度的辛伐他汀灌注有或无缺血（15分钟）和再灌注（60分钟）的离体心脏。记录心脏功能参数（如左心室舒张末压[LVDP]、+dp/dt max和-dp/dt max）、心率和冠状动脉血流量。辛伐他汀（3 - 30微摩尔/升）显著增加灌注60分钟的离体大鼠心脏的LVDP、+dp/dt max和-dp/dt max。30微摩尔/升的辛伐他汀使心率降低，10和30微摩尔/升的辛伐他汀使冠状动脉血流量增加。在100微摩尔/升的辛伐他汀浓度下，心脏功能恶化并随后发生心脏骤停。在离体缺血/再灌注（15/60分钟）大鼠心脏中，给予辛伐他汀（3 - 30微摩尔/升）通过LVDP、+dp/dt max和-dp/dt max检测到显著保留了心脏功能。辛伐他汀在30微摩尔/升时也显著降低心率，在10和30微摩尔/升时增加这些大鼠心脏的冠状动脉血流量。然而，辛伐他汀在100微摩尔/升时的保护作用转变为损伤增加。仅在15/60分钟缺血再灌注前用3微摩尔/升辛伐他汀预处理可改变LVDP、+dp/dt max和-dp/dt max。辛伐他汀预处理后心率和冠状动脉血流量均未改变。由于低于100微摩尔/升浓度的辛伐他汀对离体灌注大鼠心脏的心脏功能发挥有益作用，因此它可在心肌缺血和再灌注后立即应用。
