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Made available in DSpace on 2022-04-29T08:32:48Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-09-01 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) To gain insight on the impact of preventive exercise during pulmonary arterial hypertension (PAH), we evaluated the gene expression of myosins and gene-encoding proteins associated with the extracellular matrix remodeling of right hypertrophied ventricles. We used 32 male Wistar rats, separated in four groups: Sedentary Control (S, n = 8); Control with Training (T, n = 8); Sedentary with Pulmonary Arterial Hypertension (SPAH, n = 8); and Pulmonary Arterial Hypertension with Training (TPAH, n = 8). All rats underwent a two-week adaptation period; T and TPAH group rats then proceeded to an eight-week training period on a treadmill. At the beginning of the 11th week, S and T groups received an intraperitoneal injection of saline, and SPAH and TPAH groups received an injection of monocrotaline (60 mg/kg). Rats in the T and TPAH groups then continued with the training protocol until the 13th week. We assessed exercise capacity, echocardiography analysis, Fulton’s index, cross-sectional areas of cardiomyocytes, collagen content and types, and fractal dimension (FD). Transcript abundance of myosins and extracellular matrix genes were estimated through reverse transcription-quantitative PCR (RT-qPCR). When compared to the SPAH group, the TPAH group showed increases in functional capacity and pulmonary artery acceleration time/pulmonary ejection time ratio and decreases in Fulton’s index and cross-sectional areas of myocyte cells. However, preventive exercise did not induce alterations in col1a1 and myh7 gene expression. Our findings demonstrate that preventive exercise improved functional capacity, reduced cardiac hypertrophy, and attenuated PH development without interfering in mRNA-encoding myosin and collagen expression during PAH. Postgraduate Program in Animal Science University of Western São Paulo (UNOESTE), Presidente Prudente Department of Structural and Functional Biology Institute of Biosciences UNESP, Botucatu Postgraduate Program in Physical Exercise in Health Promotion Northern University of Paraná, Paraná Department of Physiotherapy University of Western São Paulo (UNOESTE), Presidente Prudente Department of Internal Medicine Botucatu Medical School UNESP, Botucatu Department of Structural and Functional Biology Institute of Biosciences UNESP, Botucatu Department of Internal Medicine Botucatu Medical School UNESP, Botucatu FAPESP: #2016/11344-0 FAPESP: #2018/12526-0 FAPESP: #2018/24317-7

To gain insight on the impact of preventive exercise during pulmonary arterial hypertension (PAH), we evaluated the gene expression of myosins and gene-encoding proteins associated with the extracellular matrix remodeling of right hypertrophied ventricles. We used 32 male Wistar rats, separated in four groups: Sedentary Control (S; n=8); Control with Training (T; n=8); Sedentary with Pulmonary Arterial Hypertension (SPAH; n=8); and Pulmonary Arterial Hypertension with Training (TPAH; n=8). The rats trained for thirteen weeks on a treadmill. They had two weeks of adaptation training. The PAH was induced by application of monocrotaline 60 mg/kg. Consequential right ventricular dysfunction was observed after the 10th week of training. Rats in the control group received saline application. At the end of the 13th week, echocardiography analysis confirmed cardiac dysfunction. Collagen content and organization was assessed through picrosirius red staining and fractal dimension (FD) analysis, respectively. Transcript abundance was estimated through reverse transcription-quantitative PCR (RT-qPCR). Cardiac dysfunction was confirmed by the reduction in maximum pulmonary artery velocity and pulmonary artery acceleration time. Through histomorphometric assessment, we found no differences in the interstitial collagen FD between groups. Regarding gene expression, myh7 gene expression was upregulated in the TPAH group. However, this did not occur with the S group. PAH also increased the mRNA abundance of col1a1 in the SPAH and TPAH groups. Moreover, the TPAH group showed a higher abundance of this gene when compared to the S group. With these findings, we concluded that preventive exercise had a positive impact on compensated hypertrophy during pulmonary hypertension. This can be explained in part by the modulation of the extracellular matrix and myosin gene expression in trained rats.

In patients with pulmonary hypertension(PH), right ventricular failure(RVF) is the main determinant of prognosis and a common cause of death. PH leads to compensated hypertrophy that progresses to decompensated RVF. RVF is accompanied by changes in the right ventricle(RV) and extracellular matrix(ECM). Preventive exercise has been shown to be a therapeutic approach in PH. We evaluated the influence of preventive exercise in ECM in the RV compensated hypertrophy in PH. We used male Wistar rats divided into 4 groups(n=8): Sedentary control(SC); Training control(TC); Sedentary PH(SPH); and Training PH(TPH). The rats performed the exercises for 13 weeks. PH was induced by monocrotaline(60mg/kg) during the 10th week of training, and the control rats received a saline solution. At the end of the 13th week, echocardiogram were performed, and the rats were euthanized. RV hypertrophy was assessed through histomorphometric analysis. Gene expression using RT-qPCR: colIa1(collagen type I alpha 1 chain); colIa2(collagen type I alpha 2 chain); coll3a1(collagen type III alpha 1 chain);and Mmp2 and 9(matrix metalloproteinase 2 and 9). Collagen content was assessed through picrosirius red. Our results showed increases in cardiomyocyte sectional area(SC vs. SPH,p=0.0001), peak flow velocity(SC vs. SPH,p=0.001), and gene expression of the colla1(SC vs. SPH,p=0.007). The preventive exercise normalized the peak flow velocity(SHP vs. TPH, p=0.001) and decreased the area of the cardiomyocytes(SHP vs. TPH,p=0.001). This occurred without changes in the ECM. Preventive exercise exerts a cardioprotective effect in compensated hypertrophy in monocrotaline rat model with PH(function and hypertrophy), without alterations in ECM.

Background: Brazil is the worldwide leader in the long-term use of pesticides and herbicides. This compromises the health of handlers by causing harmful neurological, respiratory, and cardiovascular changes. The herbicide 2.4D has been shown to cause cardiac overload with subsequent pathological remodeling. Objective: To analyze the cardiac morphological repercussions on the left ventricle (LV) of mice submitted to nebulization by the herbicide 2.4D. Methods: Fifteen mice were divided into three groups: control group (CG; n = 5) exposed to nebulization with sodium chloride solution; low concentration group (LCG; n = 5) exposed to nebulization of the herbicide 2.4D with 3.71 x 10-3 grams; and high concentration group (HCG; n = 5) exposed to nebulization of the herbicide 2.4D with 9.28 x 10-3 grams for 15 minutes. The fractal dimension analysis was performed through the box-counting method. Later, the ImageJ program was used to calculate the fractal dimension of each group. To evaluate cardiac remodeling, histological slides were prepared and stained with Hematoxylin-Eosin (HE). Fifty areas of cardiomyocytes were analyzed per animal. The comparisons between groups were performed by ANOVA One-Way with Tukey’s posttest (p < 0.05). Results: There was no change in fractal dimension values between the CG = 1.37 ± 0.02, LCG = 1.33 ± 0.04 and the HCG = 1.33 ± 0.07 groups. However, cardiac hypertrophy occurred in the HCG = 303.9 ± 38.80 µm(2) when compared to the CG group = 236.9 ± 61.71 µm(2) (p = 0.034). Conclusion: The herbicide 2.4D used for 72 hours did not promote cardiotoxicity when evaluated by fractal dimension. However, cardiomyocyte hypertrophy was observed in the LV.

Introdução: A Paralisia Cerebral (PC) pode estar associada á incontinência urinária (IU), que pode ser decorrente de alterações neurológicas. Objetivo: Avaliar eficácia da eletroestimulação transcutânea (TENS) do nervo tibial posterior na qualidade de vida de mulheres com IU e PC. Método: Relato de caso com duas mulheres (28 e 36 anos). Avaliado o tipo de disfunção urinária e questionário King’s Health Questionnaire (KHQ). Realizadas 20 sessões de eletroestimulação com frequência de 60 Hz, largura de pulso 200 µs, frequência da corrente de 01 Hz. A intensidade foi estabelecida de acordo com cada paciente. Resultados: Ambas diminuíram o número de idas ao banheiro e trocas dos forros. No KHQ, a paciente 1 melhorou nos domínios impacto da incontinência, limitação das tarefas, limitação física/social e medidas de segurança. Já a paciente 2, nos domínios limitações das tarefas, relações pessoais e sono/energia. Conclusão: A TENS melhorou a qualidade de vida destas mulheres.

Introduction: The early stage of Pulmonary Hypertension(PH) is characterized by right ventricular(RV) hypertrophy and decreased heart function(cardiac dysfunction), without signs and symptoms of heart failure. Nevertheless, the molecular mechanism most related to cardiac dysfunction is not yet known. Aim: to evaluate which molecular mechanism is most related to cardiac dysfunction(early stage) in rats with PH. Methods: PH was induced by a single intraperitoneal injection of monocrotaline(60mg/kg) in 16 adult male Wistar rats(4 months). The rats were divided into control(C,n=8) and PH(n=8). After three weeks, the rats were submitted to an echocardiogram to verify cardiac dysfunction and were euthanized. The molecular mechanisms evaluated were those related to collagen, myosin and calcium. The RV was examined by gene expression analysis using real-time RT-qPCR of colIa1(collagen type I alpha 1 chain), colIa2(collagen type I alpha 2 chain), myh6(myosin heavy chain 6), myh7(myosin heavy chain 7), Ryr2(ryanodine receptor), Pln(phospholamban) and atp2a2(Ca2+ ATPase of the sarcoplasmic reticulum). Results: PH rats presented RV dysfunction: decrease of 23% in the peak flow velocity of the pulmonary artery(p=0.001) and 30% in the pulmonary velocity acceleration time(p=0.005), without heart failure signs. There were decreases in the gene expressions: Ryr2(p=0.01), Pln(p=0.02), atp2a2(p=0.02) and myh6(p=0.002) in the PH group and moderate correlations between pulmonary ejection time and Pln(r=-0.71;p=0.08), atp2a2(r=-0.78;p=0.027) and Myh6(r=-0.70;p=0.13). Conclusion: in the early stage of PH the molecular mechanism most related to cardiac dysfunction was calcium genes, which can be a therapeutic target to be addressed.

Pulmonary hypertension (PH) is a serious disease that leads to cor pulmonale and right heart failure. It is still unknown the effects of preventive training in early stages of PH regarding the genes in right ventricle. Aim: to investigate preventive aerobic training effects on genes in right ventricle (RV). Methods: 32 adult male Wistar rats were divided into 4 groups (n=8): Sedentary control (S); Training control(T); Sedentary PH(SPH); Training PH(TPH). The animals trained for 13 weeks on a treadmill, being two weeks of adaptation and eleven of training. PH was induced by the application of monocrotaline (60mg/kg) during the tenth week of training, and the control animals received a saline application. Two tests of lactate threshold were performed 24 hours and 14 days after the application of monocrotaline. At the end of the thirteenth week, an echocardiogram was performed. The animals were euthanized, and the right ventricle was examined by gene expression analysis using real-time RT-qPCR of col1a1, col1a2, myh6 and myh7. Results: Cardiac dysfunction was demonstrated by the reduction of maximum speed in the pulmonary artery and acceleration time of the pulmonary artery. There was an increase of the col1a1 gene (p-value=0.008) between the groups SPH and TPH vs. S and TPH vs. T, and of the myh7 gene (p-value=0.0242) between the groups TPH vs. S. Conclusions: We concluded that at the onset of cardiac dysfunction by PH there is an increase of myh7 and col1a1 genes, and preventive training did not alleviate these genetic modifications.

Pulmonary arterial hypertension (PAH) is a chronic disease which causes overload to the right ventricle. The effect of preventive training on cardiac remodelling in this condition is still unknown. This study aimed to evaluate the influence of preventive training on hypertrophy, heart function and gene expression of calcium transport proteins in rats with monocrotaline-induced PAH. Thirty-two male Wistar rats were randomly divided into four groups: S, sedentary control; T, trained control; SM, sedentary monocrotaline; and TM, trained monocrotaline. The preventive training protocol was performed on a treadmill for 13 weeks, five times/week. The first two weeks were adopted for adaptation to training with gradual increases in speed/time. The speed of the physical training from the third to tenth weeks was gradually increased from 0.9 to 1.1 km/h for 60 min. Next, monocrotaline was applied (60 mg/kg) to induce PAH and lactate threshold analysis performed to determine the training speeds. The training speed of the TM group in the following two weeks was 0.8 km/h for 60 min and the T = 0.9 km/h for 60 min; in the final two weeks, both groups trained at the same speed and duration 0.9 km/h, 60 min. Cardiac function was assessed through echocardiography, ventricular hypertrophy through histomorphometric analysis and gene expression through RT-qPCR. Right cardiac function assessed through the peak flow velocity was SM = 75.5 cm/s vs. TM = 92.0 cm/s (P = 0.001), and ventricular hypertrophy was SM = 106.4 μm² vs. TM = 77.7 μm² (P = 0.004). There was a decrease in the gene expression of ryanodine S = 1.12 au vs. SM = 0.60 au (P = 0.02) without alterations due to training. Thus, we conclude that prior physical training exerts a cardioprotective effect on the right ventricle in the monocrotaline rat model.

Made available in DSpace on 2018-12-11T17:04:25Z (GMT). No. of bitstreams: 0 Previous issue date: 2016-07-01. Added 1 bitstream(s) on 2019-10-09T18:30:31Z : No. of bitstreams: 1 S0066-782X2016004000033.pdf: 513463 bytes, checksum: d9ba48636cd68e1b4524c887cc0e4851 (MD5) Background: Right-sided heart failure has high morbidity and mortality, and may be caused by pulmonary arterial hypertension. Fractal dimension is a differentiated and innovative method used in histological evaluations that allows the characterization of irregular and complex structures and the quantification of structural tissue changes. Objective: To assess the use of fractal dimension in cardiomyocytes of rats with monocrotaline-induced pulmonary arterial hypertension, in addition to providing histological and functional analysis. Methods: Male Wistar rats were divided into 2 groups: control (C; n = 8) and monocrotaline-induced pulmonary arterial hypertension (M; n = 8). Five weeks after pulmonary arterial hypertension induction with monocrotaline, echocardiography was performed and the animals were euthanized. The heart was dissected, the ventricles weighed to assess anatomical parameters, and histological slides were prepared and stained with hematoxylin/eosin for fractal dimension analysis, performed using box-counting method. Data normality was tested (Shapiro-Wilk test), and the groups were compared with non-paired Student t test or Mann Whitney test (p < 0.05). Results: Higher fractal dimension values were observed in group M as compared to group C (1.39 ± 0.05 vs. 1.37 ± 0.04; p < 0.05). Echocardiography showed lower pulmonary artery flow velocity, pulmonary acceleration time and ejection time values in group M, suggesting function worsening in those animals. Conclusion: The changes observed confirm pulmonary-arterial-hypertension-induced cardiac dysfunction, and point to fractal dimension as an effective method to evaluate cardiac morphological changes induced by ventricular dysfunction. UNOESTE FCT/UNESP Departamento de Fisioterapia FCT/UNESP Departamento de Educação Física UNOESTE Departamento de Morfologia UNESP Faculdade de Medicina UNESP FCT/UNESP Departamento de Fisioterapia FCT/UNESP Departamento de Morfologia UNESP Faculdade de Medicina UNESP