Villani F, Galimberti M, Monti E, Cova D, Lanza E, Rozza-Dionigi A, Favalli L, Poggi P
Divisione di Fisiopatologia Cardiorespiratoria, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milano, Italy.
Toxicol Appl Pharmacol. 1990 Feb;102(2):292-9. doi: 10.1016/0041-008x(90)90028-s.
Doxorubicin (DXR), administered iv in rats at the weekly dose of 3 mg/kg for 5 weeks, significantly impaired body weight gain and induced irreversible ECG alterations, mainly consisting of a progressive prolongation of ST and QT intervals. Five weeks after the last DXR administration, the contractile performance of atria isolated from treated animals was significantly reduced. At the same time, relevant morphologic lesions, consisting of myocyte vacuolization and myofibrillar loss, were also present in the myocardium of the same rats. The study showed that ICRF-187, administered ip at a dose of 125 mg/kg, significantly prevented body weight loss. QT and ST prolongation, and the decreased contractile force induced by DXR. In addition, ICRF-187 caused a significant reduction in incidence and severity of myocardial lesions. The cardioprotective effect of ICRF-187 is not mediated by a modification in DXR pharmacokinetics in heart, since the drug was actually found to increase DXR uptake in myocardial cells.
阿霉素（DXR）以每周3毫克/千克的剂量静脉注射给大鼠，持续5周，显著损害体重增加并引起不可逆的心电图改变，主要表现为ST段和QT间期逐渐延长。在最后一次给予DXR 5周后，从接受治疗的动物分离出的心房收缩性能显著降低。同时，相同大鼠的心肌中也存在相关的形态学病变，包括心肌细胞空泡化和肌原纤维丧失。研究表明，以125毫克/千克的剂量腹腔注射ICRF-187可显著防止体重减轻、QT和ST段延长以及由DXR引起的收缩力降低。此外，ICRF-187使心肌病变的发生率和严重程度显著降低。ICRF-187的心脏保护作用不是通过改变心脏中DXR的药代动力学来介导的，因为实际上发现该药物会增加心肌细胞对DXR的摄取。
