Exercício aeróbico na Doença de Chagas: estudo da remodelação cardíaca durante a infecção experimental em camundongos

Abstract

Chagas disease is caused by the parasite Trypanosoma cruzi, and is one of the neglected diseases of South America, recognized by the World Health Organization (WHO). Discovered in 1909 by Carlos Chagas, the pathophysiology of the disease can be divided into two phases, acute and chronic. In the acute phase there is a large expansion of the number of parasites, with chronic activation of the immune system and induction of intense myocarditis. With disease progression, in the chronic phase, the immune-mediated myocardial injury can lead to interstitial myocardial fibrosis throughout the myocardium, with consequent worsening of cardiac arrhythmias and death. Currently, the treatment of the disease is based on alleviating the symptoms. This is done in a non-specific manner and according to the guidelines of other heart diseases, which leads to general and non-specific approaches. Moderate physical exercise is known to induce resistance to infections caused by protozoa in animals and humans, working as a stimulator of immune response in the control of infection by T. cruzi, and may be an effective non-pharmacological therapy in Chagas disease. This study explores the potential of moderate intensity aerobic physical training performed pre-infection and maintained post-infection as a possible therapy in Chagas' disease, investigating the cellular and systemic bases associated in modulating the progression of experimental infection with T. cruzi. Experimental infection was carried out in Balb/c mice, randomly separated into four groups, sedentary control, sedentary chagas, trained control, trained chagas. Trained mice were subjected to a 16-week aerobic training protocol, 5 days per week, 1 hour per day, at an intensity of 60% of maximum running speed. At the end of the 8th week the animals were infected with the Colombian strain of T. cruzi. Moderate intensity physical training was able to decrease the parasitemia peak and reduce the mortality of infected animals. As a consequence, we observed a decrease in the inflammatory profile and increase in cardiomyocyte occupancy in the trained infected animals compared to the sedentary infected ones. Physical training also improved aerobic capacity, prevented weight loss, and improved electrophysiological and contractile parameters in isolated cardiomyocytes, reducing AP alternans, which correlates with decreasing the appearance and severity of cardiac arrhythmias in trained animals. Together, the results presented in this work will contribute to the elucidation of the effects of physical training on the electromechanical properties in isolated cardiomyocytes in Chagas disease. Moreover, it was possible to demonstrate the beneficial effects of physical training and thus, to propose new strategies that will contribute to the reduction of arrhythmias typical of CD, as well as the influence of moderate intensity aerobic physical training in the progression of this disease.