DOSE-EFFECT AND STRUCTURE-FUNCTION-RELATIONSHIPS IN DOXORUBICIN CARDIOMYOPATHY
DOSE-EFFECT AND STRUCTURE-FUNCTION-RELATIONSHIPS IN DOXORUBICIN CARDIOMYOPATHY
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DOI：
10.1016/0002-8703(81)90096-x
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发表时间：
1981-01-01
影响因子：
4.8
通讯作者：
DANIELS, JR
中科院分区：
文献类型：
--
作者：
BRISTOW, MR;MASON, JW;DANIELS, JR
抗癌药物阿霉素 (DXR)（阿霉素）产生的心肌病 (CM) 为分析心肌疾病发展过程中的剂量效应和结构功能关系提供了独特的机会。通过心内膜心肌活检的超微结构检查来测量形态学损伤的程度，并通过右心导管插入术来测量接受DXR的患者的性能异常程度。形态损伤是可变的，但与 100 至 600 mg/m2 之间的总累积 DXR 剂量成正比。表现异常与剂量相关性较弱，表现出曲线关系并具有表达阈值。在测量运动血流动力学的患者亚组中，导管插入异常与形态损伤密切相关（r = 0.57-0.78）；这种关系还表现出曲线、阈值配置。在 DXR-CM 中，心肌损伤与细胞毒性损伤的程度（DXR 剂量）成正比，而心肌功能得以保留，直到达到临界剂量或损伤程度，之后心肌性能迅速恶化。
Cardiomyopathy (CM) produced by the anticancer drug doxorubicin (DXR) (adriamycin) provides a unique opportunity to analyze dose-effect and structure-function relationships during development of myocardial disease. The degree of morphologic damage was measured by ultrastructural examination of endomyocardial biopsy and the degree of performance abnormality by right heart catheterization in patients receiving DXR. Morphologic damage was variable but was proportional to the total cumulative DXR dose between 100 and 600 mg/m2. Performance abnormalities correlated weakly with dose, exhibited a curvilinear relationship and had a threshold for expression. Catheterization abnormalities correlated well with morphologic damage (r = 0.57-0.78) in a subgroup of patients in whom exercise hemodynamics were measured; this relationship also exhibited a curvilinear, threshold configuration. In DXR-CM myocardial damage is proportional to the degree of cytotoxic insult (DXR dose), while myocardial function is preserved until a critical dose or degree of damage is reached, after which myocardial performance deteriorates rapidly.