Preventive aerobic training preserves sympathovagal function and improves DNA repair capacity of peripheral blood mononuclear cells in rats with cardiomyopathy

• Published in: Scientific reports Vol. 12; no. 1; p. 6422
• Main Authors: Ghignatti, Paola Victória da Costa, Russo, Mariana Kras Borges, Becker, Tiago, Guecheva, Temenouga Nikolova, Teixeira, Luciele Varaschini, Lehnen, Alexandre Machado, Schaun, Maximiliano Isoppo, Leguisamo, Natalia Motta
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 19.04.2022; Nature Publishing Group UK; Nature Portfolio
• Subjects: Aerobic capacity; Aerobics; Animal models; Animals; Bioassays; Calcium-binding protein; Cannulation; Cardiac function; Cardiomyopathies - chemically induced; Cardiomyopathy; Comet assay; Deoxyribonucleic acid; DNA; DNA damage; DNA Repair; Doxorubicin; Doxorubicin - pharmacology; Echocardiography; Exercise; Fitness training programs; Heart rate; Leukocytes, Mononuclear; Male; Peripheral blood mononuclear cells; Physical Conditioning, Animal; Physical fitness; Physical training; Rats; Rats, Inbred WKY; Troponin; Troponin T
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-022-09361-z

To evaluate the effect of preventive aerobic exercise training on sympathovagal function, cardiac function, and DNA repair capacity in a preclinical model of doxorubicin (DOX)-induced cardiomyopathy. Forty male Wistar-Kyoto rats were allocated into four groups (n = 10/group): D (DOX-treated) and C (controls) remained sedentary, and DT (DOX-trained) and CT (control-trained) performed aerobic training 4 days/week, during 4 weeks before exposure to DOX (4 mg/kg/week during 4 weeks) or saline solution. We evaluated cardiac function (echocardiography), hemodynamic and sympathovagal modulation (artery-femoral cannulation), cardiac troponin T levels, and DNA repair capacity (comet assay). Exercise training preserved ejection fraction (D: - 14.44% vs. DT: - 1.05%, p < 0.001), fractional shortening (D: - 8.96% vs. DT: - 0.27%, p = 0.025) and troponin T levels (D: 6.4 ± 3.6 vs. DT: 2.8 ± 1.7 ng/mL, p = 0.010). DOX increased heart rate variability (C: 27.7 ± 7.9 vs. D: 7.5 ± 2.2 ms , p < 0.001) and induced sympathovagal dysfunction (LF/HF, C: 0.37 ± 0.15 vs. D: 0.15 ± 0.15, p = 0.036) through exacerbation of sympathetic function (LF, C: 0.22 ± 0.01 vs. D: 0.48 ± 0.24 Hz, p = 0.019). Peripheral mononuclear blood cells of DT animals presented lower residual DNA damage (D: 43.4 ± 8.4% vs. DT: 26 ± 3.4%, p = 0.003 after 1 h). Cardioprotective effects of preventive aerobic exercise training are mediated by preservation of sympathovagal function and improvement of DNA repair capacity of peripheral blood mononuclear cells.