Asayama J, Yamahara Y, Matsumoto T, Miyazaki H, Tatsumi T, Inoue M, Ohta B, Omori I, Inoue D, Nakagawa M
Second Department of Medicine, Kyoto Prefectural University of Medicine, Japan.
Pharmacol Toxicol. 1992 Nov;71(5):371-5. doi: 10.1111/j.1600-0773.1992.tb00564.x.
To investigate the effects of doxorubicin on postextrasystolic potentiation (PESP), isolated guinea pig papillary muscles were field-stimulated and the resulting isometric force was recorded. Postextrasystolic contraction was evoked following trains of 37 regular stimulations. The effects of acute doses of doxorubicin (0.2 mM) on regular contractions and postextrasystolic contractions were examined for 2 hr. The effects of subacute doses of doxorubicin (total dose 5 mg/kg intraperitoneally) on the relationship between %PESP (postextrasystolic/regular contraction) and both the extra-stimulus coupling interval and the postextrasystolic interval were examined. Acute administration of doxorubicin decreased the amplitude of postextrasystolic contractions more than that of regular contractions. Thus, %PESP in the doxorubicin-treated group decreased significantly over time. There was no similar decrease in the control papillary muscles. Both the extra-stimulus coupling interval and the postextrasystolic interval had less of an effect on %PESP in doxorubicin-treated animals than in control animals. Since PESP depends upon sarcoplasmic reticulum activity, our results indicate that acute and subacute exposure to doxorubicin impairs the activity of the sarcoplasmic reticulum of guinea pig papillary muscles.
为研究阿霉素对期前收缩后增强（PESP）的影响，对分离的豚鼠乳头肌进行场刺激并记录产生的等长力。在37次规则刺激序列后诱发期前收缩。检测急性剂量阿霉素（0.2 mM）对规则收缩和期前收缩的影响，持续2小时。检测亚急性剂量阿霉素（腹腔注射总剂量5 mg/kg）对PESP百分比（期前收缩/规则收缩）与额外刺激耦合间期和期前收缩间期之间关系的影响。急性给予阿霉素对期前收缩幅度的降低作用大于对规则收缩幅度的降低作用。因此，阿霉素治疗组的PESP百分比随时间显著降低。对照乳头肌未出现类似降低。与对照动物相比，额外刺激耦合间期和期前收缩间期对阿霉素治疗动物的PESP百分比影响较小。由于PESP取决于肌浆网活性，我们的结果表明，急性和亚急性暴露于阿霉素会损害豚鼠乳头肌肌浆网的活性。
