Exercise training reduces cardiac fibrosis, promoting improvement in arrhythmias and cardiac dysfunction in an experimental model of Chronic Chagasic Cardiomyopathy

Alex Cleber Improta-Caria^1,2*Carolina Kymie Vasques Nonaka³Pâmela Santana Daltro³Carine Machado Azevedo⁴Breno Barreto⁴Gisele Batista Carvalho³JULIANA FRAGA VASCONCELOS⁴Bruno Solano De Freitas Souza³Simone Macambira^2*Milena Botelho Pereira Soares^4*

• ¹University of São Paulo, São Paulo, Brazil
• ²Federal University of Bahia (UFBA), Salvador, Bahia, Brazil
• ³Center for Biotechnology and Cell Therapy, São Rafael Hospital, Salvador, Brazil
• ⁴Gonçalo Moniz Institute (IGM), Salvador, Bahia, Brazil

Background: Chagas disease, caused by the parasite Trypanosoma cruzi, is associated with inflammation and fibrosis, which characterizes chronic Chagasic cardiomyopathy (CCC). CCC manifests as arrhythmias, hypertrophy or dilation of the left ventricle, and it may progress to heart failure. Therefore, interventions are needed to slow the progression of CCC. Aims: We investigated the effects of exercise training in an animal model of CCC. Methods: C57BL/6 mice infected with Trypanosoma cruzi were submitted to a progressively treadmill exercise training protocol. The cardiac function was evaluated by echocardiogram and electrocardiogram. RT-qPCR and morphometric analyses were performed on samples of cardiac tissue to quantify inflammation and fibrosis. Results: EKG analysis confirmed that all infected mice developed arrhythmias, with different degrees of severity. Exercise improved arrhythmias in 43.75% of chagasic trained mice, and the remaining mice did not show any alteration in EKG. The untrained chagasic group had no improvement in arrhythmias. The ventricular complacency in chagasic trained mice increased, as revealed by the reduction in isovolumetric relaxation time when compared to untrained mice. Exercise induced the reduction of gene expression of TGF-β, TNF-α, IL-1β, IL-6 and MMP-9 and reduced fibrosis in the heart tissue of chagasic mice. Conclusion: Exercise reduced fibrosis in the heart and skeletal muscle, favoring the improvement of arrhythmias, and augment of cardiac complacency in mice with CCC, in addition to decreasing the expression of profibrotic and proinflammatory genes in the heart.