Asayama J, Tanaka T, Tatsumi T, Nakagawa C, Kobara M, Matoba S, Ohta B, Inoue D, Nakagawa M
Second Department of Medicine, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Japan.
J Cardiovasc Pharmacol. 1995 Nov;26(5):693-7. doi: 10.1097/00005344-199511000-00004.
Clinical use of doxorubicin is limited by its cardiotoxicity. In doxorubicin-induced cardiomyopathy, vacuolization of the sarcoplasmic reticulum (SR) has been reported. We investigated whether doxorubicin had a direct action on the sarcoplasmic reticulum (SR) in isolated perfused rat hearts. The left and right atria were trimmed to maintain heart rate (HR) <200 beats/min. Postrest contractions, which are believed to be due primarily to Ca2+ release from the SR, were evoked with a programmable stimulator after variable rest intervals. The amplitude of the postrest contractions increased markedly as the rest interval increased. Doxorubicin (0.1 mM) significantly suppressed this potentiation of the postrest contractions. Furthermore, doxorubicin slowly induced aftercontractions and an increase in left ventricular diastolic pressure (LVDP), phenomena that are usually associated with ouabain intoxication. We conclude that doxorubicin-induced cardiomyopathy may be due to SR dysfunction, leading to intracellular Ca2+ overload.
阿霉素的临床应用因其心脏毒性而受到限制。在阿霉素诱导的心肌病中，已报道肌浆网（SR）出现空泡化。我们研究了阿霉素对离体灌注大鼠心脏的肌浆网（SR）是否有直接作用。修剪左右心房以维持心率（HR）<200次/分钟。在不同的静息间隔后，用可编程刺激器诱发静息后收缩，据信其主要是由于Ca2+从肌浆网释放所致。随着静息间隔的增加，静息后收缩的幅度显著增加。阿霉素（0.1 mM）显著抑制了静息后收缩的这种增强作用。此外，阿霉素缓慢诱导后收缩和左心室舒张压（LVDP）升高，这些现象通常与哇巴因中毒有关。我们得出结论，阿霉素诱导的心肌病可能是由于肌浆网功能障碍，导致细胞内Ca2+过载。
