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    Hipertrofia do ventrículo direito por bandagem da artéria pulmonar em ratos. Estudo das alterações estruturais, funcionais e genéticas
    (Universidade Federal de São Paulo (UNIFESP), 2019-12-03) Silva, Jairo Montemor Augusto [UNIFESP]; Moises, Valdir Ambrosio [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Introduction: Right ventricular remodeling with consequent functional impairment may occur in some clinical conditions in adults and children. The triggering factors, the molecular mechanisms and the evolution are not yet well known. Left ventricular changes associated with right ventricular remodeling are also poorly understood. Objectives: Evaluate RV morphological, functional and gene expression parameters in rats submitted to pulmonary artery banding compared to control rats, as well as the temporal evolution of these parameters. • Analyze the influence of RV remodeling with pulmonary artery banding in rats and their controls on LV geometry, histology, gene expression and functional performance. Methods: Healthy 6-week-old male Wistar-EPM rats weighing 170 to 200 grams were included. One day after the echocardiogram, the animals underwent the procedure for BAP or not (control) and then randomly divided into subgroups according to the follow-up time: 72 hours, 2, 4, 6 or 8 weeks. In each subgroup were performed: new echocardiogram, hemodynamic study, collection of material for morphological analysis (hypertrophy and fibrosis) and molecular biology (gene expression). Results were presented as mean ± standard deviation of the mean. The comparison between variables of the subgroups and evolution times was made with two-way ANOVA and Tukey post-test. The adopted significance level was 5%. Results: There was no significant difference between subgroups in the percentage of water in the lung and liver (lung ranged from 76% to 78% and liver from 67% to 71%). The weight of the right chambers was significantly higher in animals with BAP in all subgroups (RV BAP from 0.34 to 0.48 g and controls from 0.17 to 0.20 g, AD with BAP from 0.09 to 0.14 g and controls from 0.02 to 0.03 g). In the RV of animals with BAP, there was a significant increase in myocyte nuclear volume (97 μm3 to 183.6 μm3) compared to controls (34.2 μm3 to 57.2 μm3), which were more intense in subgroups with lower exposure to BAP; and fibrosis percentage (5.9% to 10.4% vs 0.96% to 1.18%) was as higher as the BAP time was longer. At echocardiography there was also a significant increase in myocardial thickness in all groups with BAP (0.09 to 0.11 cm compared to controls- 0.04 to 0.05 cm), but without variation in RV diastolic diameter at echocardiography. From 2 to 8 weeks of BAP, the S 'wave (0.031 cm/s and 0.040 cm/s) and VPAVD (51% to 56%), RV systolic function parameters, were significantly lower than the respective controls (0,040 cm/s a 0,050cm/s; and 61% to 67%). Furthermore, higher expression of genes related to hypertrophy and extracellular matrix in the initial subgroups and apoptosis genes in the longer time subgroups of BAP were observed in RV. On the other hand, LV weight was not different between animals with or without BAP. The nuclear volume of the animals with BAP was larger than the controls (74 μm3 to 136 μm3; from 40.8 μm3 to 46.9 μm3); and the percentage of fibrosis was significantly higher in the 4- and 8-week BAP groups (1.2 and 2.2%) compared to the controls (0.4 and 0.7%). On echocardiography, the diastolic diameter and LV myocardial thickness were not different between animals with BAP and controls. Measurements of isovolumetric relaxation time and E-wave deceleration time on echocardiography were different between animals with BAP and controls in all subgroups, but there were no changes in diastolic function at hemodynamic study. There was also increased expression of genes related to various functions, in particular hypertrophy. Conclusion: 1) Rats submitted to pulmonary artery banding presented remodeling of RV compatible with hypertrophy. These alterations were mediated by increased expression of several genes and accompanied by functional alterations; coincident with the onset fibrosis. 2) Structural changes of the RV such as weight, myocardial thickness, myocyte nuclear volume and degree of fibrosis were modified according to the time of exposure to pulmonary artery banding and were related to variations in gene expression; Highlighting the change from alpha to beta pattern from early to late times. 3) The study suggests that the left ventricle developed histological alterations accompanied by modifications of gene expression simultaneously to the alterations found in the right ventricle.