Mitochondrial Antioxidant Plastomitin Improves Cardiac Function in Doxorubicin-Induced Cardiomyopathy

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.