Abramov A A, Lakomkin V L, Prosvirnin A V, Lukoshkova E V, Kapelko V I
National Medical Research Center for Cardiology.
Kardiologiia. 2019 Jun 25;59(6):35-41. doi: 10.18087/cardio.2019.6.2649.
The aim of the study was to ascertain whether the use of plastomitin, the mitochondrial antioxidant, can affect the development of systolic dysfunction that occurs in rats after 4 weeks of doxorubicin treatment (2 mg/kg weekly). Materials and methods. Male Wistar rats weighing 320-380 g were used in this work. Echocardiographic study was carried out using Vevo 1100 with linear probe 13-24 MHz frequency. Results. Echocardiographic study of rats through 8 weeks from the beginning of doxorubicin treatment showed the presence of systolic dysfunction with decrease of ejection fraction of the left ventricle (LV) by 32%. Hearts of rats, to which plastomitin (0.32 mg/kg daily) was administered simultaneously with doxorubicin, showed significantly increased ejection fraction and shortening fraction as compared with doxorubicin group, and these values were close to the control. In experiments with simultaneous registration of LV pressure and volume, it was found that the hearts of all rats treated with doxorubicin showed reduced contractility index and stroke work, while maintaining normal cardiac output. Such compensation in experiments with treatment with doxorubicin alone was achieved through significant reduction in the peripheral resistance, slowing of myocardial relaxation, and facilitation of LV diastolic filling during prolonged diastolic pause (the heart rate was slowed by 23%). In experiments with simultaneous application of doxorubicin and plastomitin, the compensation was achieved through preservation of myocardial contractility and relaxability, the heart rate and peripheral resistance. This method of compensation is more beneficial for the body, because it does not restrict the supply of organs and tissues with oxygen, and has significant advantage over doxorubicin group at equal heart rate. Conclusion. The results allow to conclude that the use of plastomitin together with doxorubicin prevents the development of doxorubicin-induced systolic dysfunction.
本研究的目的是确定使用线粒体抗氧化剂质体丝蛋白是否会影响多柔比星治疗4周（每周2mg/kg）后大鼠发生的收缩功能障碍的发展。材料与方法。本研究使用体重为320 - 380g的雄性Wistar大鼠。使用频率为13 - 24MHz的线性探头的Vevo 1100进行超声心动图研究。结果。从多柔比星治疗开始8周后对大鼠进行的超声心动图研究显示存在收缩功能障碍，左心室射血分数降低了32%。与多柔比星组相比，同时给予质体丝蛋白（每日0.32mg/kg）的大鼠心脏射血分数和缩短分数显著增加，且这些值接近对照组。在同步记录左心室压力和容积的实验中，发现所有接受多柔比星治疗的大鼠心脏收缩指数和每搏功降低，而心输出量保持正常。单独使用多柔比星治疗的实验中，这种代偿是通过显著降低外周阻力、减慢心肌舒张以及在延长的舒张期停顿期间促进左心室舒张期充盈（心率减慢23%）来实现的。在同时应用多柔比星和质体丝蛋白的实验中，代偿是通过保留心肌收缩性和舒张性、心率和外周阻力来实现的。这种代偿方法对身体更有益，因为它不会限制器官和组织的氧气供应，并且在相同心率下比多柔比星组具有显著优势。结论。结果表明，质体丝蛋白与多柔比星联合使用可预防多柔比星诱导的收缩功能障碍的发展。
