Grimm D, Elsner D, Schunkert H, Pfeifer M, Griese D, Bruckschlegel G, Muders F, Riegger G A, Kromer E P
Klinik und Poliklinik für Innere Medizin II, Universität Regensburg, Germany.
Cardiovasc Res. 1998 Jan;37(1):91-100. doi: 10.1016/s0008-6363(97)00212-5.
High dosages of catecholamines induce cardiomyocyte necrosis and interstitial fibrosis in rats. We investigated whether this initial damage is followed by the development of heart failure and assessed the particular role of the renin-angiotensin system using ramipril.
Following the administration of 0 mg or 150 mg isoproterenol/kg 6 groups of Wistar rats were followed for 2 or 16 weeks: Sham, isoproterenol, isoproterenol + ramipril. Isoproterenol induced significant increases of echocardiographically measured left ventricular end-diastolic posterior wall thickness and dimension, whereas ramipril treatment significantly attenuated these changes. Left ventricular end-diastolic pressure was markedly increased in isoproterenol-treated rats and normalized following ramipril. Isoproterenol rats were further characterized by hormonal activations including transient elevations of plasma renin activity, aldosterone and cardiac angiotensin converting enzyme activity. Histomorphological characterization of isoproterenol-treated hearts demonstrated cardiomyocyte necrosis and reparative fibrosis. Ramipril treatment only slightly reduced the amount of necrosis as well as the expression of extracellular matrix proteins.
In rats, a toxic dosage of isoproterenol caused characteristic myocardial damage that subsequently resulted in mild heart failure. Ramipril administration following isoproterenol was highly effective to attenuate hemodynamic and hormonal alterations as well as the development of left ventricular hypertrophy, but had only little influence on the expression of extracellular matrix proteins. Since angiotensin converting enzyme inhibition had no impact on the initial myocardial injury, the development of heart failure in this model seems to require functional integrity of the renin-angiotensin system.
高剂量儿茶酚胺可诱导大鼠心肌细胞坏死和间质纤维化。我们研究了这种初始损伤之后是否会发展为心力衰竭，并使用雷米普利评估肾素-血管紧张素系统的特殊作用。
给6组Wistar大鼠分别注射0 mg或150 mg异丙肾上腺素/kg，随后观察2周或16周，分组为：假手术组、异丙肾上腺素组、异丙肾上腺素+雷米普利组。异丙肾上腺素导致超声心动图测量的左心室舒张末期后壁厚度和内径显著增加，而雷米普利治疗可显著减轻这些变化。异丙肾上腺素处理的大鼠左心室舒张末期压力明显升高，雷米普利治疗后恢复正常。异丙肾上腺素处理的大鼠还表现出激素激活，包括血浆肾素活性、醛固酮和心脏血管紧张素转换酶活性的短暂升高。对异丙肾上腺素处理的心脏进行组织形态学特征分析，显示心肌细胞坏死和修复性纤维化。雷米普利治疗仅略微减少了坏死量以及细胞外基质蛋白的表达。
在大鼠中，有毒剂量的异丙肾上腺素导致特征性心肌损伤，随后导致轻度心力衰竭。异丙肾上腺素给药后使用雷米普利可有效减轻血流动力学和激素改变以及左心室肥厚的发展，但对细胞外基质蛋白的表达影响很小。由于血管紧张素转换酶抑制对初始心肌损伤没有影响，该模型中心力衰竭的发展似乎需要肾素-血管紧张素系统的功能完整性。
