Avaliação do músculo diafragma em ratos com insuficiência cardíaca submetidos à exercício físico aeróbio: estudo experimental e revisão sistemática com meta-análise

Abstract

Heart Failure (HF) is a major public health problem and one of the leading causes of hospitalization and death. Symptoms include dyspnea, exercise intolerance, and worsening of functional capacity. Morphological, biomechanical, enzymatic and functional changes can be seen in the respiratory muscles and can act to promote diaphragmatic dysfunction through the alteration of muscle strength, which may occur due to an increase in oxidative stress. The objective of this study was to investigate in the diaphragm muscle the influence of aerobic exercise on muscle strength, oxidative stress and signaling pathways of Ik-B and NADPH. Thirty-two male Wistar rats were divided into four experimental groups: Sham (control); ShamExF (aerobic exercise control); AoS (aortic stenosis); EAoExF (aerobic exercise aortic stenosis). The animals performed an exercise program for 5 days / week for 10 / weeks. Cardiac abnormalities were assessed by echocardiography (18 and 28 weeks). In the diaphragm muscle the oxidative stress dosage was measured by means of Lipid Peroxidation (MDA), Protein Carbonylation, and the analysis of Antioxidant Enzymes were done through Superoxide Dismutase (SOD) and Catalase. Ik-B pathway analysis by Western blot protein expression and the NADPH pathway subunits (NOX2, NOX4, P22phox and P47phox) were measured by gene expression by real-time RT-PCR. At the same time, a systematic review with meta-analysis was carried out, which began with a search for key words in 3 databases (Pubmed, Embase and Web of Science) for the selection of studies and to analyze the diaphragmatic muscle strength of rats with heart failure submitted to aerobic exercise. The risk of bias was assessed through Syrcle application. All phases were done in duplicate. At the end, the meta-analysis was done. The echocardiogram performed at 28 weeks demonstrated atrial size (LA/FBW) was 11% lower in AS-Ex animals compared to AS. Functionally, the animals in the AS-Ex group demonstrated improvement in systolic dysfunction compared AS, observed through 10% lower ESP% and 22% lower PWSS. Were observed in the Tei Index (53% higher) and TDI's (20% lower), evidencing the improvement in the cardiac function parameters of AS-Ex compared to AS. The results of oxidative stress evaluations via IK-B and p-47phox did not differ. In the gene expression of the NADPH oxidase complex the p22phox subunit was lower in 30.8% in the EaoExF group than in the EAo. The expression of Nox2 was 27.7% lower in the EAoExF group, compared to AoS. There was a 36.3% decrease in Nox4 in the EAoExF group compared to EAo. The results of the meta-analysis showed that aerobic exercise did not favor diaphragmatic strength gain. In view of the above, we concluded that the protocol of aerobic physical exercise does not influence diaphragmatic strength, and in rats with HF due to aortic stenosis, the exercise was able to minimize the cardiac dysfunction and the oxidative stress of the diaphragm muscle.