Key result
Plastomitin prevents doxorubicin-induced diastolic dysfunction, improving LV relaxation rate by ~51%.
Why the study?
Diastolic dysfunction is an increasing form of chronic heart failure lacking effective therapy, necessitating the development of means for its correction.
Does plastomitin prevent diastolic dysfunction in a rat model of doxorubicin-induced cardiomyopathy?
Does plastomitin prevent diastolic dysfunction in a rat model of doxorubicin-induced cardiomyopathy?
Absolute Event Rate: 10480% vs 6950%
p-value: p=<0.05
In a preclinical model, the mitochondria-targeted antioxidant plastomitin prevented doxorubicin-induced diastolic dysfunction, offering a potential strategy for mitigating chemotherapy-induced cardiotoxicity.
Hypothesis-generating for plastomitin in doxorubicin cardiotoxicity; does not support clinical adoption without human trials.
Aim An attempt to prevent the development of diastolic dysfunction (DD) with the mitochondrial antioxidant plastomitin on a model of doxorubicin-induced cardiomyopathy. DD is a type of chronic heart failure. Due to the increasing number of patients with this condition and the absence of effective therapy, development of means for DD correction is a relevant objective.Material and methods Cardiomyopathy was modeled in 17 rats by two subcutaneous injections of doxorubicin 2 mg/kg/week. The other group (n=17), also administered with doxorubicin, received plastomicin 0.32 mg/kg daily subcutaneously. Left ventricular function was evaluated with echocardiography (EchoCG) and cardiac catheterization with simultaneous pressure and volume monitoring.Results According to EchoCG data the ejection fraction remained unchanged in the experimental groups. Cardiac catheterization showed disorders of both myocardial contractility and relaxability only in the doxorubicin group.Conclusion A course of plastomitin in combination with the doxorubicin treatment can maintain normal heart contractility and thereby, prevent the known doxorubicin cardiotoxicity.
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Lakomkin et al. (2020) studied Doxorubicin-induced cardiomyopathy (n=49). Plastomitin vs. Doxorubicin alone was evaluated on Maximal rate of left ventricular pressure decrease (p=<0.05). Plastomitin prevented doxorubicin-induced diastolic dysfunction, significantly improving the maximal rate of LV pressure decrease compared to doxorubicin alone (10480 vs 6950 mmHg/s, p<0.05).
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