Anderson T J, Meredith I T, Uehata A, Mudge G H, Selwyn A P, Ganz P, Yeung A C
Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115.
Circulation. 1993 Sep;88(3):1093-100. doi: 10.1161/01.cir.88.3.1093.
Detection of transplant coronary disease remains difficult. Both intravascular ultrasound (IVUS) imaging and functional coronary vasomotion studies have been used to evaluate this process. However, the time course of intimal thickening as assessed by IVUS and the relation between structure and function have not been explored.
In 40 patients 1 to 8 years after transplantation, 108 coronary artery segments were analyzed by IVUS. Intimal index [% intimal area (lumen+intimal area)] and maximal thickness were used to quantify intimal thickening. Abnormal IVUS was present in 53 of 108 segments (49%) (mean intimal index of diseased segments, 23 +/- 2%; maximal thickness, 530 +/- 47 microns). For those patients with intimal thickening in all segments of the analyzed artery, more time had elapsed since transplantation (4.3 +/- 0.6 years) than for those whose arteries contained some normal (2.6 +/- 0.3 years) or all normal segments (2.2 +/- 0.6 years, P < .05). Both the proportion of segments with intimal thickening and the degree of thickening increased as a function of time after transplantation (P < .5). By multivariate analysis, the independent predictors of intimal thickening were increasing time after transplantation and pretransplantation hypercholesterolemia (P = .02). Within the cohort of 40 patients, endothelium-dependent vasomotor function was evaluated in 26 matched segments from 11 patients studied 1 year after transplantation and in 15 matched segments from 8 patients studied > or = 5 years after transplantation by serial infusions of acetylcholine (10(-8) to 10(-6) mol/L). Of the 26 segments assessed for structure/function correlation at 1 year after transplantation, 22 had no intimal thickening by IVUS. However, endothelial dysfunction was present in 13 of these normal segments (mean diameter constriction, 18.8 +/- 2.3%). Of the 15 segments studied > or = 5 years after transplantation, 11 had intimal thickening. Nine of these 11 segments had preserved endothelial function (mean diameter dilation, 8.6 +/- 2.9%). There was no relation between the degree of intimal thickening and the magnitude of the endothelium-dependent response to acetylcholine.
This study has shown that intimal thickening after transplantation begins as a heterogeneous process and increases in extent and magnitude over time. Also, endothelial dysfunction occurs early before the intimal thickening; yet in those patients surviving > or = 5 years, endothelial function may recover even in the presence of moderate intimal pathology. The variable relation between intimal pathology and endothelial function is probably a result of the episodic nature of immune injury.
移植后冠状动脉疾病的检测仍然困难。血管内超声（IVUS）成像和冠状动脉血管运动功能研究均已用于评估此过程。然而，IVUS评估的内膜增厚的时间进程以及结构与功能之间的关系尚未得到探索。
对40例移植后1至8年的患者，通过IVUS分析了108个冠状动脉节段。内膜指数[内膜面积百分比（管腔+内膜面积）]和最大厚度用于量化内膜增厚。108个节段中有53个（49%）存在异常IVUS（病变节段的平均内膜指数为23±2%；最大厚度为530±47微米）。对于分析动脉所有节段均有内膜增厚的患者，自移植后经过的时间（4.3±0.6年）比动脉含有一些正常节段（2.6±0.3年）或所有节段均正常的患者（2.2±0.6年）更长（P<0.05）。内膜增厚节段的比例和增厚程度均随移植后时间的延长而增加（P<0.5）。多因素分析显示，内膜增厚的独立预测因素为移植后时间延长和移植前高胆固醇血症（P=0.02）。在40例患者队列中，对11例移植后1年研究的患者的26个匹配节段以及对8例移植后≥5年研究的患者的15个匹配节段，通过连续输注乙酰胆碱（10⁻⁸至10⁻⁶mol/L）评估内皮依赖性血管运动功能。在移植后1年评估结构/功能相关性的26个节段中，22个通过IVUS无内膜增厚。然而，这些正常节段中有13个存在内皮功能障碍（平均直径收缩率为18.8±2.
