Anthracyclines cause endothelial injury in pediatric cancer patients: A pilot study
Anthracyclines cause endothelial injury in pediatric cancer patients: A pilot study
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DOI：
10.1200/jco.2005.03.5956
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发表时间：
2006-02-20
影响因子：
45.3
通讯作者：
Rosenthal, DN
中科院分区：
文献类型：
--
作者：
Chow, AY;Chin, C;Rosenthal, DN
目的血管内皮在调节动脉血管舒缩张力、释放一氧化氮以舒张血管方面发挥着核心作用。可以使用高分辨率超声测量肱动脉直径的变化来在体内评估内皮依赖性血管舒张。动物研究表明，蒽环类药物会损害内皮细胞并损害动脉的血管舒张反应；然而，在人类中没有可比较的数据。这是一项评估蒽环类药物对儿科癌症患者的内皮毒性的初步研究。患者和方法对 14 名对照患者和 14 名癌症患者（4 至 21 岁）进行了研究。癌症患者在研究前2至60个月完成了含有不少于300 mg/m(2)蒽环类药物的化疗。在休息时和血压袖带闭塞后 1 分钟测量肱动脉直径。肱动脉反应性 (BAR) 计算为基线与袖带放气测量后之间的百分比变化。使用未配对的双尾 t 检验对结果进行比较。结果 两组之间的基线特征（包括年龄、女性比例、血压和静息血管直径）相似。对照组的 BAR 平均为 6.7%，标准差 (SD) 为 3.3%，而接受蒽环类药物治疗的患者的 BAR 平均为 3.8%，SD 为 3.4%，表明治疗组血管舒缩反应性显着降低 (P < .05)。 结论 这些结果表明，蒽环类药物会导致内皮功能受损，这是一种重要的、新近认识的毒性。由于内皮功能障碍是动脉粥样硬化形成的早期事件，因此这些发现可能具有重要的临床意义。需要进一步的研究来在更大的队列中证实这些初步结果。
Purpose The vascular endothelium plays a central role in the regulation of arterial vasomotor tone, releasing nitric oxide for vasodilation. Endothelial-dependent vasodilation can be assessed in vivo, using high resolution ultrasound to measure changes in diameter of the brachial artery. Animal studies have demonstrated that anthracyclines can damage the endothelium and impair the vasodilatory response of arteries; however, there are no comparable data in humans. This is a pilot study assessing endothelial toxicity from anthracyclines in pediatric cancer patients.Patients and Methods Fourteen control patients and 14 cancer patients (4 to 21 years) were studied. Cancer patients had completed chemotherapy containing no less than 300 mg/m(2) of anthracyclines 2 to 60 months before study. Brachial artery diameters were measured at rest and 1 minute after blood pressure cuff occlusion. Brachial artery reactivity (BAR) was calculated as percent change between baseline and after cuff deflation measurements. Results were compared using unpaired, two-tailed t-test.Results Baseline characteristics, including age, percentage of females, blood pressure, and resting vessel diameters were similar between the two groups. BAR in the controls averaged 6.7% with a standard deviation (SD) of 3.3%, while BAR in patients receiving anthracyclines averaged 3.8% with an SD of 3.4%, demonstrating a significant decrease (P < .05) in vasomotor reactivity in the treated group.Conclusion These results suggest that anthracyclines cause impaired endothelial function, an important and newly recognized toxicity. Since endothelial dysfunction is an early event in atherogenesis, there may be important clinical implications from these findings. Further study is required to confirm these preliminary results in a larger cohort.