Bauersachs Johann, Hiss Katrin, Fraccarollo Daniela, Laufs Ulrich, Ruetten Hartmut
Medizinische Klinik und Poliklinik I, Universitätsklinikum, Universität Würzburg, Germany.
Cardiovasc Res. 2006 Dec 1;72(3):438-46. doi: 10.1016/j.cardiores.2006.08.014. Epub 2006 Aug 30.
Hypercholesterolemia contributes to coronary artery disease progression but little is known about its effect on left ventricular (LV) function after myocardial infarction (MI). The aim of this study was to investigate the effects of hypercholesterolemia and statin treatment in rabbits with experimental MI.
New Zealand White rabbits on a normal or cholesterol-rich diet for 4 weeks, underwent permanent coronary artery ligation. Starting on the first day post-MI rabbits were treated with either placebo or simvastatin (5 mg/kg/day) for 9 weeks. Hypercholesterolemia itself did not affect LV function in sham-operated animals but further impaired LV systolic (dP/dtmax -42%) and diastolic (dP/dtmin -47%) function in MI rabbits on placebo. Simvastatin treatment not only prevented deterioration of LV function associated with hypercholesterolemia but improved LV function (dP/dtmax +130%; dP/dtmin +144%, P < 0.05). Simvastatin also attenuated the depression of LV function in normocholesterolemic MI rabbits (dP/dtmax +46%; dP/dtmin +53%, P < 0.05). Hypercholesterolemia in MI rabbits coincided with a significant increase in C-reactive protein levels (marker of inflammation) and Rac1-GTPase activity (marker of oxidative stress), and a reduction in cardiac sarcoplasmic-reticulum calcium ATPase-2 expression and endothelial nitric oxide synthase protein phosphorylation, all of which were normalised by simvastatin treatment. Elevated serum cholesterol levels were only partially reduced by simvastatin.
Hypercholesterolemia further impaired the depressed LV function in rabbits post-MI. Statin treatment reversed this effect, and conferred additional protection, as in normocholesterolemic animals. Our study suggests that anti-inflammatory and anti-oxidative effects of simvastatin substantially contribute to its beneficial effects on cardiac function after MI.
高胆固醇血症会促进冠状动脉疾病进展，但对于其在心肌梗死（MI）后对左心室（LV）功能的影响知之甚少。本研究旨在探讨高胆固醇血症及他汀类药物治疗对实验性MI家兔的影响。
将新西兰白兔分为正常饮食组和高胆固醇饮食组，喂养4周后进行永久性冠状动脉结扎。MI术后第一天开始，家兔分别接受安慰剂或辛伐他汀（5mg/kg/天）治疗9周。高胆固醇血症本身对假手术动物的LV功能无影响，但会进一步损害接受安慰剂治疗的MI家兔的LV收缩功能（dP/dtmax降低42%）和舒张功能（dP/dtmin降低47%）。辛伐他汀治疗不仅可预防与高胆固醇血症相关的LV功能恶化，还能改善LV功能（dP/dtmax增加130%；dP/dtmin增加144%，P<0.05）。辛伐他汀还可减轻正常胆固醇血症MI家兔的LV功能抑制（dP/dtmax增加46%；dP/dtmin增加53%，P<0.05）。MI家兔的高胆固醇血症与C反应蛋白水平（炎症标志物）和Rac1 - GTP酶活性（氧化应激标志物）显著增加以及心肌肌浆网钙ATP酶-2表达和内皮型一氧化氮合酶蛋白磷酸化降低同时出现，而辛伐他汀治疗可使所有这些指标恢复正常。辛伐他汀仅部分降低了升高的血清胆固醇水平。
高胆固醇血症会进一步损害MI后家兔已受抑制的LV功能。他汀类药物治疗可逆转这种效应，并如在正常胆固醇血症动物中一样提供额外保护。我们的研究表明，辛伐他汀的抗炎和抗氧化作用对其MI后对心脏功能的有益作用有很大贡献。
