Pelikan P C, Weisfeldt M L, Jacobus W E, Miceli M V, Bulkley B H, Gerstenblith G
J Cardiovasc Pharmacol. 1986 Sep-Oct;8(5):1058-66.
The acute effects of doxorubicin on coronary perfusion and left ventricular pressures and intracellular phosphate metabolite levels, the latter obtained by 31P nuclear magnetic resonance, were measured simultaneously in isolated, isovolumic rat hearts (Langendorf preparation) perfused at constant flow. Nineteen experimental hearts were perfused for 70 min with oxygenated HEPES-buffered solution containing 6 mg/L doxorubicin. These were compared with 18 control hearts (C), perfused under identical conditions but without doxorubicin, by repeated measures analysis of variance. In the experimental group, coronary perfusion pressure steadily increased to 226.3 +/- 13.8% (mean +/- SEM) of initial levels (p less than 0.0001 vs. C). Because flow was constant, the increase in coronary perfusion pressure in experimental hearts indicates a greater than twofold increase in coronary resistance. Intracellular phosphocreatine and ATP decreased to 80.3 +/- 3.9% (p less than 0.005 vs. C) and 82.1 +/- 6.4% (p less than 0.05 vs. C), whereas inorganic phosphate increased to 149.7 +/- 19.1% (p less than 0.05 vs. C) of initial levels, respectively. Accompanying these changes, diastolic pressure steadily increased to 521.7 +/- 91.4% of initial levels (p less than 0.0001 vs. C). Developed pressure initially increased to 107.1 +/- 4.5% at 30 min, and thereafter decreased to 76.2 +/- 6.3% at 70 min (p less than 0.05 vs. C). Typical structural alterations in myocyte nuclei were noted. Cellular calcium was not increased in doxorubicin-exposed hearts. Thus, acute doxorubicin cardiotoxicity is characterized by an increase in coronary resistance and is closely correlated with alterations in ventricular function and a decrease in intracellular high-energy phosphate content.(ABSTRACT TRUNCATED AT 250 WORDS)
在恒流灌注的离体等容大鼠心脏（Langendorf 制备）中，同时测量了阿霉素对冠状动脉灌注、左心室压力以及细胞内磷酸盐代谢物水平（通过 31P 核磁共振获得）的急性影响。19 个实验心脏用含 6mg/L 阿霉素的氧合 HEPES 缓冲溶液灌注 70 分钟。通过重复测量方差分析，将这些心脏与 18 个对照心脏（C）进行比较，对照心脏在相同条件下灌注但不含阿霉素。在实验组中，冠状动脉灌注压稳步升至初始水平的 226.3±13.8%（平均值±标准误）（与 C 组相比，p<0.0001）。由于流量恒定，实验心脏中冠状动脉灌注压的升高表明冠状动脉阻力增加了两倍多。细胞内磷酸肌酸和 ATP 分别降至初始水平的 80.3±3.9%（与 C 组相比，p<0.005）和 82.1±6.4%（与 C 组相比，p<0.05），而无机磷酸盐则升至初始水平的 149.7±19.1%（与 C 组相比，p<0.05）。伴随这些变化，舒张压稳步升至初始水平的 521.7±91.4%（与 C 组相比，p<0.0001）。心室内压最初在 30 分钟时升至 107.1±4.5%，此后在 70 分钟时降至 76.2±6.3%（与 C 组相比，p<0.05）。观察到心肌细胞核有典型的结构改变。暴露于阿霉素的心脏中细胞内钙未增加。因此，急性阿霉素心脏毒性的特征是冠状动脉阻力增加，且与心室功能改变和细胞内高能磷酸盐含量降低密切相关。（摘要截短于 250 字）
