Cardioprotective effects of exercise training on doxorubicin-induced cardiomyopathy: a systematic review with meta-analysis of preclinical studies

Ghignatti, Pvdc and Nogueira, L. J. and Lehnen, A. M. and Leguisamo, N. M.

Sci Rep (2021) 11: 6330

DOI: 10.1038/s41598-021-83877-8

Abstract

Doxorubicin (DOX)-induced cardiotoxicity in chemotherapy is a major treatment drawback. Clinical trials on the cardioprotective effects of exercise in cancer patients have not yet been published. Thus, we conducted a systematic review and meta-analysis of preclinical studies for to assess the efficacy of exercise training on DOX-induced cardiomyopathy. We included studies with animal models of DOX-induced cardiomyopathy and exercise training from PubMed, Web of Sciences and Scopus databases. The outcome was the mean difference (MD) in fractional shortening (FS, %) assessed by echocardiography between sedentary and trained DOX-treated animals. Trained DOX-treated animals improved 7.40% (95% CI 5.75-9.05, p \textless 0.001) in FS vs. sedentary animals. Subgroup analyses revealed a superior effect of exercise training execution prior to DOX exposure (MD = 8.20, 95% CI 6.27-10.13, p = 0.010). The assessment of cardiac function up to 10 days after DOX exposure and completion of exercise protocol was also associated with superior effect size in FS (MD = 7.89, 95% CI 6.11-9.67, p = 0.020) vs. an echocardiography after over 4 weeks. Modality and duration of exercise, gender and cumulative DOX dose did were not individually associated with changes on FS. Exercise training is a cardioprotective approach in rodent models of DOX-induced cardiomyopathy. Exercise prior to DOX exposure exerts greater effect sizes on FS preservation.

Citation

Ghignatti, P., Nogueira, L. J., Lehnen, A. M., & Leguisamo, N. M. (2021). Cardioprotective effects of exercise training on doxorubicin-induced cardiomyopathy: a systematic review with meta-analysis of preclinical studies. Sci Rep, 11(1), 6330. https://doi.org/10.1038/s41598-021-83877-8 Animals, Male, Rats, Female, Humans, Rats, Sprague-Dawley, Physical Conditioning, Animal, Echocardiography, *Exercise, Cardiomyopathies/chemically induced/pathology/*therapy, Cardiotoxicity/pathology/prevention & control/therapy, Doxorubicin/*adverse effects/therapeutic use, Heart/drug effects/physiopathology, Neoplasms/complications/pathology/*therapy

Keywords

• Animals
• Male
• Rats
• Female
• Humans
• Rats
• Sprague-Dawley
• Physical Conditioning
• Animal
• Echocardiography
• *Exercise
• Cardiomyopathies/chemically induced/pathology/*therapy
• Cardiotoxicity/pathology/prevention & control/therapy
• Doxorubicin/*adverse effects/therapeutic use
• Heart/drug effects/physiopathology
• Neoplasms/complications/pathology/*therapy