Farrar D J, Bond M G, Riley W A, Sawyer J K
Department of Physiology, Bowmann Gray School of Medicine, Wake Forest University, Winston-Salem, N.C.
Circulation. 1991 May;83(5):1754-63. doi: 10.1161/01.cir.83.5.1754.
We noninvasively measured changes in average aortic stiffness in 79 cynomolgus monkeys being fed cholesterol progression, regression, and control diets by measuring pulse wave velocity (PWV) in 260 experiments during a 30-month period. Every 6 months, a group of monkeys was studied with invasive aortic PWV techniques and with ultrasonically determined pressure-strain elastic modulus (Ep) of the carotid artery, and then the group was killed so that morphometric evaluation of atherosclerosis severity could be made. After 6 months of a cholesterol progression diet, PWV decreased slightly from 6.2 +/- 0.1 to 5.7 +/- 0.1 m/sec, followed by an approximate linear increase to 8.8 +/- 1.2 m/sec after 30 months on the diet. The corresponding ratio of intimal (plaque) area to medial area (IA/MA) measured on perfusion-fixed cross-sections of the abdominal and thoracic aortas increased from 0.16 +/- 0.07 at 6 months to 1.23 +/- 0.22 at 30 months. Monkeys in the regression groups were fed the cholesterol progression diet for 18 months, followed by a chow diet for 6 or 12 months. In the first 6 months of the cholesterol regression diet, PWV continued to increase from 7.0 +/- 0.2 to 8.1 +/- 0.4 m/sec, and IA/MA was 1.24 +/- 0.18. However, after 12 months of the cholesterol regression diet, PWV decreased to 6.8 +/- 0.4 m/sec, and IA/MA was 0.90 +/- 0.18. The variability of the data demonstrates that PWV is not a simple function of atherosclerosis severity, and the best simple correlation was r = 0.69 (r2 = 0.48) between PWV and intimal area. However, multiple regression analysis of aortic PWV, systolic (SP) and diastolic (DP) blood pressures, and total plasma cholesterol concentration (TPC), all of which can be measured with minimally invasive techniques, improved the prediction of the IA/MA ratio through the following equation: IA/MA = 0.127 PWV-0.039 DP+0.023SP+0.0003TPC-0.292 (r = 0.81, r2 = 0.66). These data suggest that arterial stiffness in combination with minimally invasive parameters can be used to predict the severity of diffuse asymptomatic atherosclerosis in monkeys. However, more widespread application of these data to humans is uncertain because of biological variability and differences between animal models and human subjects.
我们通过在30个月内进行的260次实验中测量脉搏波速度（PWV），对79只食蟹猴在摄入胆固醇递增、递减和对照饮食期间的平均主动脉僵硬度变化进行了无创测量。每6个月，对一组猴子采用有创主动脉PWV技术以及超声测定颈动脉的压力应变弹性模量（Ep）进行研究，然后将该组猴子处死，以便对动脉粥样硬化严重程度进行形态学评估。在摄入胆固醇递增饮食6个月后，PWV从6.2±0.1米/秒略有下降至5.7±0.1米/秒，随后在该饮食持续30个月后近似线性增加至8.8±1.2米/秒。在腹部和胸部主动脉灌注固定横切面上测量的内膜（斑块）面积与中膜面积之比（IA/MA）从6个月时的0.16±0.07增加至30个月时的1.23±0.22。回归组的猴子先摄入胆固醇递增饮食18个月，然后摄入普通饮食6或12个月。在胆固醇递减饮食的前6个月，PWV继续从7.0±0.2米/秒增加至8.1±0.4米/秒，IA/MA为1.24±0.18。然而，在胆固醇递减饮食12个月后，PWV降至6.8±0.4米/秒，IA/MA为0.90±0.18。数据的变异性表明PWV并非动脉粥样硬化严重程度的简单函数，PWV与内膜面积之间的最佳简单相关性为r = 0.69（r2 = 0.48）。然而，对主动脉PWV、收缩压（SP）和舒张压（DP）以及总血浆胆固醇浓度（TPC）进行多元回归分析，所有这些均可通过微创技术测量，通过以下方程改善了对IA/MA比值的预测：IA/MA = 0.127PWV - 0.039DP + 0.023SP + 0.0003TPC - 0.292（r = 0.81，r2 = 0.66）。这些数据表明，动脉僵硬度与微创参数相结合可用于预测猴子弥漫性无症状动脉粥样硬化的严重程度。然而，由于生物学变异性以及动物模型与人类受试者之间的差异，这些数据在人类中的更广泛应用尚不确定。
