Anversa P, Li P, Malhotra A, Zhang X, Herman M V, Capasso J M
Department of Medicine, New York Medical College, Valhalla 10595.
Am J Physiol. 1993 Aug;265(2 Pt 2):H713-24. doi: 10.1152/ajpheart.1993.265.2.H713.
In an attempt to elucidate the effects of two major risk factors of heart failure in humans, high blood pressure and coronary artery disease, renal hypertension and coronary artery constriction were induced singularly and in combination in rats, and the functional, structural, and biochemical alterations of the myocardium were examined 12-13 wk later. Renal hypertension (RH), coronary narrowing (CN), and their association (NH) resulted in left ventricular failure demonstrated by a significant increase in left ventricular end-diastolic pressure, a decrease in +dP/dt and -dP/dt, and a reduction in stroke volume and cardiac output. Measurements of ventricular loading documented that RH was characterized by elevations in systolic and diastolic wall stress of 42 and 160%, respectively. Corresponding changes with NH were 80 and 315%. CN was accompanied by an augmentation of diastolic wall stress only (280%). The abnormalities in mural stress were coupled with reductions in systolic and diastolic wall thickness-to-chamber radius ratios of 39 and 29% after CN. These anatomic parameters were preserved with RH, whereas the systolic wall thickness-to-chamber radius ratio was reduced 31% with NH. Structurally, multiple foci of replacement fibrosis were found with each intervention. The sites of tissue injury and their volume percent in the myocardium were comparable with CN and RH but were significantly more numerous and occupied a larger fraction of the ventricular wall in the presence of NH. Biochemically, the calcium dose-response curve of myofibrillar Mg2+ adenosinetriphosphatase (ATPase) activity did not vary with CN, RH, and NH. In contrast, a marked decrease in Ca2+ myosin ATPase activity was found in NH rats in association with a shift in myosin isoenzymes from V1 to V3. In conclusion, multiple physiological, morphological, and biochemical factors may participate in the generation of the abnormalities in ventricular loading with hypertension and/or coronary artery stenosis.
为了阐明人类心力衰竭的两个主要危险因素——高血压和冠状动脉疾病的影响，分别单独及联合诱导大鼠发生肾性高血压和冠状动脉狭窄，并在12 - 13周后检查心肌的功能、结构和生化改变。肾性高血压（RH）、冠状动脉狭窄（CN）及其联合作用（NH）导致左心室衰竭，表现为左心室舒张末期压力显著升高、+dP/dt和 -dP/dt降低、每搏输出量和心输出量减少。心室负荷测量表明，RH的特征是收缩期和舒张期壁应力分别升高42%和160%。NH的相应变化为80%和315%。CN仅伴有舒张期壁应力增加（280%）。CN后，壁应力异常与收缩期和舒张期壁厚度与腔半径比值分别降低39%和29%相关。这些解剖学参数在RH时得以保留，而NH时收缩期壁厚度与腔半径比值降低31%。在结构上，每种干预均发现多个替代性纤维化病灶。心肌组织损伤部位及其体积百分比在CN和RH时相当，但在NH存在时明显更多且占据心室壁的比例更大。在生化方面，肌原纤维Mg2+ 三磷酸腺苷酶（ATP酶）活性的钙剂量反应曲线在CN、RH和NH时无变化。相反，在NH大鼠中发现Ca2+ 肌球蛋白ATP酶活性显著降低，同时肌球蛋白同工酶从V1转变为V3。总之，多种生理、形态和生化因素可能参与高血压和/或冠状动脉狭窄时心室负荷异常的发生。
