Maeda A, Honda M, Kuramochi T, Takabatake T
Fourth Department of Internal Medicine, Shimane Medical University, Izumo, Japan.
Jpn Circ J. 1998 Jul;62(7):505-11. doi: 10.1253/jcj.62.505.
We examined intracellular calcium transients of isolated single cardiac myocytes from rats with doxorubicin (DOX)-induced cardiomyopathy with simultaneous measurement of cell motion. DOX was administered i.p. to Sprague-Dawley rats at 2.5 mg/kg once a week for 10 weeks. Field-stimulated calcium transients and simultaneous cell motion in single myocytes were measured in the presence or absence of isoproterenol using fura-2/AM. Histopathologic examination revealed slight changes. The time courses of both calcium transients and cell motion were significantly prolonged by DOX. There was a slight but not significant reduction in parameters of contractility in both calcium transients and cell motion. The beta-adrenoceptor responsiveness of both calcium transients and cell motion was not significantly impaired compared with the controls. Our data indicated that, despite the slight histologic changes in the heart in DOX-induced cardiomyopathy, impaired sequestration of intracellular free calcium ions in individual myocytes may be one factor leading to diastolic dysfunction. Monitoring of diastolic function is important to detect early cardiotoxicity caused by DOX.
我们检测了阿霉素（DOX）诱导的心肌病大鼠分离的单个心肌细胞的细胞内钙瞬变，并同时测量了细胞运动。将DOX以2.5mg/kg的剂量腹腔注射给Sprague-Dawley大鼠，每周一次，共10周。使用fura-2/AM在有无异丙肾上腺素的情况下测量单个心肌细胞的场刺激钙瞬变和同时的细胞运动。组织病理学检查显示有轻微变化。DOX使钙瞬变和细胞运动的时间进程均显著延长。钙瞬变和细胞运动的收缩性参数均有轻微但不显著的降低。与对照组相比，钙瞬变和细胞运动的β-肾上腺素能受体反应性均未受到显著损害。我们的数据表明，尽管DOX诱导的心肌病心脏有轻微的组织学变化，但单个心肌细胞内游离钙离子的隔离受损可能是导致舒张功能障碍的一个因素。监测舒张功能对于检测DOX引起的早期心脏毒性很重要。
