Mirsky I, Pfeffer J M, Pfeffer M A, Braunwald E
Circ Res. 1983 Dec;53(6):767-78. doi: 10.1161/01.res.53.6.767.
Female spontaneously hypertensive and normotensive rats were studied at 6, 12, 18, and 24 months of age to determine which characteristics of myocardial performance herald the onset of left ventricular dysfunction. Peak ejection fraction index was derived from measurements of peak stroke volume (in vivo volume loading) and passive pressure-volume relations. The myocardial stiffness constant (km, slope of the incremental modulus-stress relation, EINC = km sigma), chamber stiffness constant (kc, slope of the chamber stiffness-pressure relation, dP/dV = kcP), and left ventricular cavitary volume-to-wall volume ratio at 10 mm Hg) were calculated from the pressure-volume data and the contractile state was assessed from the ejection fraction index-afterload relations. In the normotensive rats, the myocardial stiffness constant was not affected by age, whereas, in the spontaneously hypertensive rats, the myocardial stiffness constant remained within normal limits until 18 months, at which time a significant increase in this index of myocardial stiffness occurred. Baseline and maximal cardiac indices and ejection fraction index of spontaneously hypertensive rats were normal from 6 to 18 months, but were markedly reduced at 24 months. This reduction in cardiac performance was associated with a decrease in the left ventricular chamber stiffness constant, i.e., kc. This decreased chamber stiffness, which occurred at a time when myocardial stiffness was increased, was due to a greater increase in cavity size than in myocardial stiffness. The left ventricular cavity-to-wall volume ratio of normotensive rats was not affected by age, whereas, in the spontaneously hypertensive rats, this ratio markedly declined by 18 months. The ejection fraction index-afterload relations i.e., a measure of the contractile state, of the 6- and 12-month-old spontaneously hypertensive rats were similar to those of the normotensive rats of all ages. However, a depression in the contractile state of the spontaneously hypertensive rats occurred at 18 months and was further depressed at 24 months. This abnormality of the contractile state was evident before the deterioration of cardiac performance, as reflected in a decrease in baseline and maximal cardiac indices, and dilation of the left ventricle occurred. The contractile state (ejection fraction index-afterload relation) is thus the most sensitive indicator of left ventricular dysfunction in spontaneously hypertensive rats.
对雌性自发性高血压大鼠和正常血压大鼠在6、12、18和24月龄时进行研究，以确定心肌性能的哪些特征预示着左心室功能障碍的发生。射血分数峰值指数来自于心搏量峰值（体内容量负荷）和被动压力-容量关系的测量。心肌硬度常数（km，增量模量-应力关系的斜率，EINC = kmσ）、心室硬度常数（kc，心室硬度-压力关系的斜率，dP/dV = kcP）以及10 mmHg时的左心室腔容积与壁容积比，根据压力-容量数据计算得出，收缩状态则根据射血分数指数-后负荷关系进行评估。在正常血压大鼠中，心肌硬度常数不受年龄影响，而在自发性高血压大鼠中，心肌硬度常数在18个月前一直保持在正常范围内，此时该心肌硬度指数出现显著增加。自发性高血压大鼠的基线和最大心脏指数以及射血分数指数在6至18个月时正常，但在24个月时显著降低。心脏功能的这种降低与左心室腔硬度常数即kc的降低有关。这种心室硬度降低发生在心肌硬度增加之时，是由于腔大小的增加幅度大于心肌硬度的增加幅度。正常血压大鼠的左心室腔与壁容积比不受年龄影响，而在自发性高血压大鼠中，该比值在18个月时显著下降。6个月和12个月大的自发性高血压大鼠的射血分数指数-后负荷关系，即收缩状态的一种度量，与所有年龄段的正常血压大鼠相似。然而，自发性高血压大鼠在18个月时出现收缩状态降低，并在24个月时进一步降低。这种收缩状态异常在心脏功能恶化之前就已明显，表现为基线和最大心脏指数降低以及左心室扩张。因此，收缩状态（射血分数指数-后负荷关系）是自发性高血压大鼠左心室功能障碍最敏感的指标。
