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Bandagem ajustável do tronco pulmonar: comparação de dois métodos de hipertrofia aguda do ventrículo sub-pulmonar; Adjustable pulmonary trunk banding: comparison of two methods of acute subpulmonary ventricle hypertrophy

Rodriguez, Miguel Alejandro Quintana
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Tese de Doutorado Formato: application/pdf
Publicado em 19/09/2006 PT
Relevância na Pesquisa
66.3%
O preparo do ventrículo sub-pulmonar através da bandagem do tronco pulmonar (TP) pode ser aplicado nos pacientes portadores de transposição das grandes artérias (TGA) que perderam a chance da cirurgia no período neonatal ou naqueles já submetidos à correção no plano atrial (Senning ou Mustard) e ainda nos portadores de transposição corrigida das grandes artérias (TCGA), que evoluíram com disfunção do ventrículo direito (sistêmico). Nesses casos, a bandagem do TP poderá induzir a hipertrofia do ventrículo sub-pulmonar (ventrículo esquerdo) na TGA, habilitando-o para o manuseio da circulação sistêmica após a cirurgia de Jatene. Entretanto, durante o preparo do ventrículo esquerdo (VE), observa-se elevada morbimortalidade, provavelmente relacionada a uma sobrecarga aguda de pressão, não tolerada pelo ventrículo. Isto se deve à dificuldade em ajustar o diâmetro da bandagem do TP, realizada em condições não fisiológicas, com o paciente anestesiado e com o tórax aberto. O objetivo deste trabalho foi o de comparar a eficiência de dois protocolos experimentais de sobrecarga pressórica contínua e intermitente do ventrículo direito (VD) para induzir a hipertrofia rápida do ventrículo subpulmonar. Foram utilizados 21 cabritos jovens (30 a 60 dias de idade)...

Análise do processo de adaptação ventricular após bandagem do tronco pulmonar em animais adultos; Study of right ventricles adaptation process following pulmonary artery banding in adult animals

Miana, Leonardo Augusto
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Tese de Doutorado Formato: application/pdf
Publicado em 06/11/2009 PT
Relevância na Pesquisa
66.58%
Pacientes portadores de transposição das grandes artérias submetidos previamente. Correção cirúrgica no plano atrial ou transposição corrigida das grandes artérias freqüentemente evoluem com disfunção do ventrículo direito morfológico. Para estes casos, tem sido proposta a correção anatômica, chamada cirurgia de Double Switch ou dupla inversão, invariavelmente realizada na adolescência ou na idade adulta. Com isso, grande parte destes pacientes necessita preparar o ventrículo esquerdo, através da bandagem do tronco pulmonar. Várias são as dificuldades no preparo do miocárdio adulto e resultados desapontadores são relatados nestes indivíduos. O objetivo deste trabalho foi promover e analisar o processo de adaptação do ventrículo direito em modelo animal adulto, comparando o método de bandagem fixa, utilizado tradicionalmente na prática clínica, com um novo método de bandagem intermitente, por um período de quatro semanas. Foram utilizadas 18 cabras adultas, divididas Em três grupos: Chama (n = 6, peso = 26,42. 2,63 Kg, bandagem frouxa, sem sobrecarga sistólica), Fixo (n = 6, peso = 26,33 . 2,32 kg, bandagem convencional com sobrecarga sistólica contínua do ventrículo direito)...

Análise da função ventricular direita em dois protocolos de treinamento com bandagem ajustável do tronco pulmonar; Assessment of right ventricular function in two training protocols with adjustable pulmonary banding

Favaro, Gustavo Antonio Guimarães
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Tese de Doutorado Formato: application/pdf
Publicado em 13/12/2011 PT
Relevância na Pesquisa
66.33%
A transposição das grandes artérias (TGA) com septo interventricular (SIV) íntegro tem como correção ideal a cirurgia de Jatene no período neonatal. Caso o paciente não seja operado nesse período, o ventrículo esquerdo pode-se tornar despreparado para sustentar a circulação sistêmica. O treinamento do ventrículo subpulmonar, através da bandagem do tronco pulmonar (TP), é uma opção terapêutica nestes casos, preparando para posterior correção definitiva. A hipótese da realização de uma bandagem pulmonar com estresse sistólico ajustável para treinar o ventrículo subpulmonar minimizaria as inadequações da bandagem convencional e aperfeiçoaria o preparo destes ventrículos. Estudos prévios desta linha de pesquisa não evidenciaram diferenças funcionais, na condição de repouso, entre os dois protocolos de preparo ventricular com sobrecarga contínua e intermitente. O objetivo do presente estudo foi o de analisar a função ventricular durante o processo de hipertrofia ventricular aguda e as repercussões na função sistólica e diastólica do ventrículo direito (VD), em condições de repouso e estresse farmacológico, em animais jovens, submetidos a dois protocolos de sobrecarga pressórica ajustável...

Metabolic Disturbances in Male Broilers of Different Strains. 1. Performance, Mortality, and Right Ventricular Hypertrophy

Gonzales, Elisabeth; Buyse, Johan; Takita, Tânia Sayuri; Sartori, José Roberto; Decuypere, Eddy
Fonte: Universidade Estadual Paulista Publicador: Universidade Estadual Paulista
Tipo: Artigo de Revista Científica Formato: 1646-1653
ENG
Relevância na Pesquisa
66.26%
Two trials were carried out to test the susceptibility for metabolic disturbances of different strains of male broilers. In Trial 1, 1,890 male chickens were allotted in a randomized block design with seven treatments (Arbor Acres, Avian Farms, Cobb-500, Hubbard-Peterson, ISA, Naked Neck, and Ross) and six blocks of 45 chickens. Trial 2 involved 2,184 male chickens of six strains (Arbor Acres, Avian Farms, Cobb 500, Hubbard-Peterson, ISA Naked Neck, and Ross) allotted in seven complete blocks of 52 birds. The same management system was adopted for all birds, reared up to 42 d in an open house during late winter (Trial 1) or late autumn (Trial 2). The most marked differences observed among the strains tested was the lower BW and higher feed conversion of Naked Neck broilers. Total percentage mortalities were high among the most productive broilers, being more than 50% due to sudden death (SDS) and ascites syndrome (AS). No Naked Neck birds died as a consequence of these disturbances and the total mortalities were significantly lower (P ≤ 0.05) than the other strains. The ratio of right ventricle weight to total ventricle weight of the dead birds was over 0.25, except for Naked Neck birds, which presented a nonhypertrophic ratio. The two trials confirmed the relationship between high productivity and high incidence of SDS and AS and indicated that Naked Neck male broilers are resistant to these metabolic disturbances.

Protective effect of left ventricular hypertrophy in right coronary artery occlusions

Gomes,Marne de Freitas; Gottschall,Carlos Antônio Mascia
Fonte: Sociedade Brasileira de Cardiologia - SBC Publicador: Sociedade Brasileira de Cardiologia - SBC
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/02/1999 EN
Relevância na Pesquisa
66.38%
OBJECTIVE: To test the hypothesis that left ventricular hypertrophy (LVH) reduces the electrocardiographic and functional effects of right coronary artery occlusion. METHODS: We analysed 215 patients (166 males and 49 women,age of 58.9±10.6 years), with occlusion of the right coronary artery without other associated lesions. There was no significant difference (p>0.05) in age and gender distribution between the 78 patients with LVH (left ventricular mass >100g/m²) (Group A) when compared with the 137 patients without LVH (left ventricular mass <100g/m²) (Group B). RESULTS: The electrocardiographic finding of transmural necrosis was more often found in group B patients than in group A patients (56.9% and 30.8%, respectively; p<0.05). The left ventricular function parameters of group A were better than those of group B: the ratio end-diastolic pressure/systolic pressure (EDP/SP) (A: 0.108±0.036; B: 0.121±0.050; p<0.05); the end-diastolic volume index (A: 75.9±31.3ml/m²; B: 88.0±31.0ml/m²; p<0.01); the end-systolic volume index (A: 16.0±10.0ml/m²; B: 27.0 ±20.0ml/m²; p<0.001); the ejection fraction (A 78.6±10.8%; B 67.7±17.9%; p<0.001); the anteroinferior shortening (A: 43.9±10.3%; B: 35.1±12.8%; p<0.001). A higher degree of coronary tortuosity was observed in group A than in group B (78.2% and 24.1%; p<0.001) and also a more frequent absent or minimal diaphragmatic hypokinetic area (A: 80.8%; B: 54.0%; p<0.05). CONCLUSION: LVH reduces the effects of myocardial sequela and protects LV function when right coronary occlusion develops.

Right ventricular structure and function as possible determinants of surgical outcome 30 years after repair of tetralogy of Fallot

Mesquita,Sonia F.; Snitcowsky,Raquel; Lopes,Antonio Augusto
Fonte: Sociedade Brasileira de Cardiologia - SBC Publicador: Sociedade Brasileira de Cardiologia - SBC
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/11/2003 EN
Relevância na Pesquisa
66.23%
OBJECTIVE: To identify the variables that may be involved in the persistence of symptoms (functional class II, III, or IV vs. I) in patients being followed up for 30 years after surgical repair of tetralogy of Fallot. METHODS: Fifty-three patients (27 women), who underwent corrective surgery for tetralogy of Fallot between 1960 and 1970, were studied. Their ages ranged from 7 months to 26 years. At the end of follow-up, 13 patients were asymptomatic and the remaining were in functional class II (N=24), III (N=15), and IV (N=1). To differentiate asymptomatic from symptomatic patients, the following variables were analyzed: age at surgery, need for widening the pulmonary ring and trunk, need for a second (2nd OP) or 3rd operation, residual defect of the interventricular septum, residual regurgitation of the pulmonary valve, systolic gradient through the right ventricular outflow tract, right ventricular dilation or hypertrophy (RVH), cardiothoracic index (CTI), right and left ventricular ejection fraction (RVEF/LVEF), and arrhythmias. RESULTS: The univariate analysis showed an association between the presence of symptoms and the 2nd OP (P=0.03), an increase in the CTI (P=0.0001), moderate to severe RVH (P=0.002), and dilation (P=0.0003). In the logistic regression model...

Diverse effects of renal denervation on ventricular hypertrophy and blood pressure in DOCA-salt hypertensive rats

Cabral,A.M.; Silva,I.F.; Gardioli,C.R.; Mauad,H.; Vasquez,E.C.
Fonte: Associação Brasileira de Divulgação Científica Publicador: Associação Brasileira de Divulgação Científica
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/04/1998 EN
Relevância na Pesquisa
66.34%
Cardiac hypertrophy that accompanies hypertension seems to be a phenomenon of multifactorial origin whose development does not seem to depend on an increased pressure load alone, but also on local growth factors and cardioadrenergic activity. The aim of the present study was to determine if sympathetic renal denervation and its effects on arterial pressure level can prevent cardiac hypertrophy and if it can also delay the onset and attenuate the severity of deoxycorticosterone acetate (DOCA)-salt hypertension. DOCA-salt treatment was initiated in rats seven days after uninephrectomy and contralateral renal denervation or sham renal denervation. DOCA (15 mg/kg, sc) or vehicle (soybean oil, 0.25 ml per animal) was administered twice a week for two weeks. Rats treated with DOCA or vehicle (control) were provided drinking water containing 1% NaCl and 0.03% KCl. At the end of the treatment period, mean arterial pressure (MAP) and heart rate measurements were made in conscious animals. Under ether anesthesia, the heart was removed and the right and left ventricles (including the septum) were separated and weighed. DOCA-salt treatment produced a significant increase in left ventricular weight/body weight (LVW/BW) ratio (2.44 ± 0.09 mg/g) and right ventricular weight/body weight (RVW/BW) ratio (0.53 ± 0.01 mg/g) compared to control (1.92 ± 0.04 and 0.48 ± 0.01 mg/g...

Effects of exerimental right ventricular hypertrophy on myocardial blood flow in conscious dogs.

Murray, P A; Baig, H; Fishbein, M C; Vatner, S F
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /08/1979 EN
Relevância na Pesquisa
66.43%
The effects of right ventricular hypertrophy on the overall and regional distribution of myocardial blood flow in the absence of an elevated coronary arterial driving pressure were evaluated in 18 concscious dogs subjected to a chronic pressure overload of the right ventricle induced by pulmonary artery constriction. The sustained pressure overload for duration of 4--6 wk or 4--5 mo resulted in significant increases in right ventricular mass (45 and 110%, respectively) and right ventricular fiber diameter (22 and 60%, respectively). Moreover, the presence of moderate and severe hypertrophy was associated with marked increases in transmural blood flow per gram to the right ventricle proportional to the observed increases in mass, i.e., of 36 and 109%, respectively, from a normal value of 0.67 +/- 0.04 ml/min per g, whereas left ventricular blood flow remained unaltered from a normal value of 1.00 +/- 0.06 ml/min per g. Despite the large increase in blood flow per gram to moderately and severely hypertrophied right ventricle, no significant changes in the ratio of capillary:muscle fiber number were observe. These data suggest that the development of right ventricular hypertroph is characterized by a sustained compensatory response of the coronary circulation to the augmented work load and mass...

Right ventricular hypertrophy in a group of coalworkers.

Fernie, J M; Douglas, A N; Lamb, D; Ruckley, V A
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /06/1983 EN
Relevância na Pesquisa
66.57%
The prevalence of right ventricular hypertrophy was studied in necropsy material from 215 coalworkers, a group which consisted of 115 men with simple or no pneumoconiosis and 100 with progressive massive fibrosis. Right ventricular hypertrophy was considered to be present if the ratio of the weight of the left ventricle plus septum to that of the right ventricle was less than 2:1. The prevalence of right ventricular hypertrophy was low (15%) in the absence of progressive massive fibrosis and appeared to be related to emphysema or airways disease or both, and not to simple pneumoconiosis. It was evident only in subjects who had smoked. In subjects with progressive massive fibrosis the prevalence of right ventricular hypertrophy was higher (34%) and it was occasionally seen in non-smokers. The prevalence increased with increasing size of lesion, and for any given size of lesion subjects with right ventricular hypertrophy had more panacinar emphysema than those without right ventricular hypertrophy. There was no relationship, however, between the extent of massive lesions or amount and type of emphysema and the degree of right ventricular hypertrophy.

Postoperative thallium-201 myocardial images. Evidence of regression of right ventricular hypertrophy in man.

Yamazaki, H; Tsugu, T; Handa, S; Takagi, Y; Ohsuzu, F; Kondo, M; Kubo, A; Inoue, T; Nakamura, Y
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /10/1982 EN
Relevância na Pesquisa
66.46%
Thallium-201 myocardial scintigraphic studies were performed on 24 patients with chronic right ventricular overload before and after surgical correction of haemodynamic overload. The ages of the patients ranged from 20 to 65 years (mean 39 years) at operation. The degree of right ventricular visualisation remained essentially unchanged in an early postoperative study (four to 60 days), though a decrease in right ventricular cavity size was noted in patients with right ventricular volume overload. On later follow-up (18 to 36 months), thallium uptake in the right ventricle was definitely less than before operation in all 13 patients studied at this time. Because thallium-201 radioactivity reflects myocardial blood flow and mass, our study indicates that right ventricular hypertrophy is largely reversible. Thus, thallium-201 myocardial scintigraphy can be used to assess non-invasively regression of right ventricular hypertrophy in patients with right ventricular overload.

The superoxide dismutase mimetic, tempol, blunts right ventricular hypertrophy in chronic hypoxic rats

Elmedal, Britt; de Dam, Mette Y; Mulvany, Michael John; Simonsen, Ulf
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
66.3%
The purpose of this study was to investigate whether a membrane-permeable superoxide dismutase mimetic, tempol, added either alone or in combination with the nitric oxide (NO) donor molsidomine, prevents the development of pulmonary hypertension (PH) in chronic hypoxic rats.Chronic hypobaric hypoxia (10% oxygen) for 2 weeks increased the right ventricular systolic pressure (RVSP), right ventricle and lung wet weight. Relaxations evoked by acetylcholine (ACh) and the molsidomine metabolite SIN-1 were impaired in isolated proximal, but not distal pulmonary arteries, from chronic hypoxic rats.Treatment with tempol (86 mg kg−1 day−1 in drinking water) normalized RVSP and reduced right ventricular hypertrophy, while systemic blood pressure, lung and liver weights, and blunted ACh relaxation of pulmonary arteries were unchanged.Treatment with molsidomine (15 mg kg−1 day−1 in drinking water) had the same effects as tempol, except that liver weight was reduced, and potassium and U46619-evoked vasoconstrictions in pulmonary arteries were increased. Combining tempol and molsidomine did not have additional effects compared to tempol alone. ACh relaxation in pulmonary arteries was not normalized by these treatments.The media to lumen diameter ratio of the pulmonary arteries was greater for the hypoxic rats compared to the normoxic rats...

Reliability of Echocardiography in the Diagnosis of Right Ventricular Hypertrophy

Prakash, Ravi
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /08/1982 EN
Relevância na Pesquisa
66.25%
The right ventricular (RV) wall thickness and dimension were measured by the technique of echocardiography in 62 patients. Thirty-six of these patients died, and the RV wall thickness was measured at necropsy for comparison with the echocardiographic measurements. The necropsy RV wall thickness measured 3.3 ± 0.6 mm in patients without right ventricular hypertrophy (RVH) and 5.9 ± 0.9 mm in patients with RVH (P<.01). The echocardiographic measurements of the diastolic RV wall thickness correlated well with the necropsy measurements of the RV wall thickness (r=.83). The sensitivity and specificity of the echocardiographic criteria in detecting RVH was superior to the electrocardiographic (ECG) criteria. Furthermore, the echocardiographic technique was useful in evaluating RVH in 18 patients with an abnormal ECG due to right or left bundle branch block or myocardial infarction. We conclude that echocardiography is reliable in diagnosing RVH.

Right coronary artery becomes stiffer with increase in elastin and collagen in right ventricular hypertrophy

Garcia, Marisa; Kassab, Ghassan S.
Fonte: American Physiological Society Publicador: American Physiological Society
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
66.19%
Changes in blood flow influence the structure, function, mechanical properties, and remodeling of arteries. The objective of the present study was to investigate the role of increased blood flow on the biaxial incremental elastic moduli of the porcine right coronary artery (RCA) and to determine the microstructural basis for the changes in moduli. We hypothesized that an increase in RCA flow will lead to increased stiffness in conjunction with remodeling of elastin and collagen in the vessel wall. The control and experimental groups consisted of five RCA vessels each. The RCA of the experimental group was exposed to 4 wk of flow-overload in right ventricular hypertrophy induced by pulmonary artery banding. Stress-strain relationships were determined and the incremental elastic moduli were derived in the circumferential, axial, and cross directions. The results show a significant increase in the elastic moduli in the circumferential (262.7 ± 15.7 vs. 120.2 ± 12.4 kPa; P < 0.001), axial (177.8 ± 25.5 vs. 100.3 ± 11.9 kPa; P = 0.025), and cross directions (104.8 ± 8.2 vs. 68.2 ± 8.6 kPa; P = 0.016) of the experimental RCA compared with controls. Multiphoton microscopy was used to assess the changes in elastin and collagen content in the media and adventitia of the vessel wall. We found a significant increase in elastin and collagen area fraction particularly in the adventitial layer. These data suggest stiffening of the vessel wall as a result of increased elastin and more predominantly collagen.

Elevated oxidative stress and endothelial dysfunction in right coronary artery of right ventricular hypertrophy

Lu, Xiao; Dang, Charles Q.; Guo, Xiaomei; Molloi, Sabee; Wassall, Cynthia D.; Kemple, Marvin D.; Kassab, Ghassan S.
Fonte: American Physiological Society Publicador: American Physiological Society
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
66.19%
Remodeling of right coronary artery (RCA) occurs during right ventricular hypertrophy (RVH) induced by banding of the pulmonary artery (PA). The effect of RVH on RCA endothelial function and reactive oxygen species (ROS) in vessel wall remains unclear. A swine RVH model (n = 12 pigs) induced by PA banding was used to study RCA endothelial function and ROS level. To obtain longitudinal coronary hemodynamic and geometric data, digital subtraction angiography was used during the progression of RVH. Blood flow in the RCA increased by 82% and lumen diameter of RCA increased by 22% over a 4-wk period of RVH. The increase in blood flow and the commensurate increase in diameter resulted in a constant wall shear stress in RCA throughout the RVH period. ROS was elevated by ∼100% in RCA after 4 wk of PA banding. The expressions of p47phox, NADPH oxidase (NOX1, NOX2, and NOX4) were upregulated in the range of 20–300% in RCA of RVH. The endothelial function was compromised in RCA of RVH as attributed to insufficient endothelial nitric oxide synthase cofactor tetrahydrobiopterin. In vivo angiographic analysis suggests an increased basal tone in the RCA during RVH. In conclusion, stretch due to outward remodeling of RCA during RVH (at constant wall shear stress)...

Dynamic microRNA expression during the transition from right ventricular hypertrophy to failure

Reddy, Sushma; Zhao, Mingming; Hu, Dong-Qing; Fajardo, Giovanni; Hu, Shijun; Ghosh, Zhumur; Rajagopalan, Viswanathan; Wu, Joseph C.; Bernstein, Daniel
Fonte: American Physiological Society Publicador: American Physiological Society
Tipo: Artigo de Revista Científica
EN
Relevância na Pesquisa
66.35%
MicroRNAs (miRs) are small, noncoding RNAs that are emerging as crucial regulators of cardiac remodeling in left ventricular hypertrophy (LVH) and failure (LVF). However, there are no data on their role in right ventricular hypertrophy (RVH) and failure (RVF). This is a critical question given that the RV is uniquely at risk in patients with congenital right-sided obstructive lesions and in those with systemic RVs. We have developed a murine model of RVH and RVF using pulmonary artery constriction (PAC). miR microarray analysis of RV from PAC vs. control demonstrates altered miR expression with gene targets associated with cardiomyocyte survival and growth during hypertrophy (miR 199a-3p) and reactivation of the fetal gene program during heart failure (miR-208b). The transition from hypertrophy to heart failure is characterized by apoptosis and fibrosis (miRs-34, 21, 1). Most are similar to LVH/LVF. However, there are several key differences between RV and LV: four miRs (34a, 28, 148a, and 93) were upregulated in RVH/RVF that are downregulated or unchanged in LVH/LVF. Furthermore, there is a corresponding downregulation of their putative target genes involving cell survival, proliferation, metabolism, extracellular matrix turnover...

Cardiomyocyte-Specific Overexpression of HEXIM1 Prevents Right Ventricular Hypertrophy in Hypoxia-Induced Pulmonary Hypertension in Mice

Yoshikawa, Noritada; Shimizu, Noriaki; Maruyama, Takako; Sano, Motoaki; Matsuhashi, Tomohiro; Fukuda, Keiichi; Kataoka, Masaharu; Satoh, Toru; Ojima, Hidenori; Sawai, Takashi; Morimoto, Chikao; Kuribara, Akiko; Hosono, Osamu; Tanaka, Hirotoshi
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Publicado em 31/12/2012 EN
Relevância na Pesquisa
66.4%
Right ventricular hypertrophy (RVH) and right ventricular (RV) contractile dysfunction are major determinants of prognosis in pulmonary arterial hypertension (PAH) and PAH remains a severe disease. Recently, direct interruption of left ventricular hypertrophy has been suggested to decrease the risk of left-sided heart failure. Hexamethylene bis-acetamide inducible protein 1 (HEXIM1) is a negative regulator of positive transcription elongation factor b (P-TEFb), which activates RNA polymerase II (RNAPII)-dependent transcription and whose activation is strongly associated with left ventricular hypertrophy. We hypothesized that during the progression of PAH, increased P-TEFb activity might also play a role in RVH, and that HEXIM1 might have a preventive role against such process. We revealed that, in the mouse heart, HEXIM1 is highly expressed in the early postnatal period and its expression is gradually decreased, and that prostaglandin I2, a therapeutic drug for PAH, increases HEXIM1 levels in cardiomyocytes. These results suggest that HEXIM1 might possess negative effect on cardiomyocyte growth and take part in cardiomyocyte regulation in RV. Using adenovirus-mediated gene delivery to cultured rat cardiomyocytes, we revealed that overexpression of HEXIM1 prevents endothelin-1-induced phosphorylation of RNAPII...

Gene Deletion of VIP Leads to Increased Mortality Associated with Progressive Right Ventricular Hypertrophy

Szema, Anthony M.; Hamidi, Sayyed A.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em 01/04/2014 EN
Relevância na Pesquisa
66.22%
Vasoactive Intestinal Peptide (VIP) knockout mice exhibit asthma, pulmonary hypertension, and left ventricular wall thinning. Humans with these disorders have premature death. We show here that VIP KO mice have reduced survival (100% mortality at 20 months), vs. 100% survival among WT C57BL/6 mice. Moreover, the ratios of weights of right ventricle divided by left ventricle plus septum were progressively increased in VIP KO mice with age. Core temperatures were lower in VIP KO mice when compared to WT littermates, with an associated pro-inflammatory cytokine milieu. Overall, our results indicate that VIP is important for survival in mice. Its absence leads to increased mortality, with progressive right ventricular hypertrophy as a surrogate of pulmonary hypertension, lower body weight, hypothermia, and pro-inflammatory milieu. These studies support VIP as a novel therapeutic agent in pulmonary hypertension.

Triggering the succinate receptor GPR91 enhances pressure overload-induced right ventricular hypertrophy

Yang, Lei; Yu, Di; Fan, Huan-Huan; Feng, Yu; Hu, Liang; Zhang, Wei-Yan; Zhou, Kai; Mo, Xu-Ming
Fonte: e-Century Publishing Corporation Publicador: e-Century Publishing Corporation
Tipo: Artigo de Revista Científica
Publicado em 15/08/2014 EN
Relevância na Pesquisa
66.17%
Background: Pulmonary arterial hypertension (PAH) leads to pressure overload in the right ventricle (RV) and induces right ventricular hypertrophy (RVH). GPR91 is an orphan G-protein-coupled receptor (GPCR) that has been characterized as a receptor for succinate, which increases in RVH; however, its role remains unknown. Methods and results: We studied succinate-GPR91 signaling in a pulmonary arterial banding (PAB) model of RVH in the SD rats due to pressure overload. We report that GPR91 was located in cardiomyocytes. We found that the expressions of GPR91 and p-Akt in the RV significantly increased in the PAB model compared with the sham. In the PAB rats, the treatment of succinate further increased the p-Akt levels and aggravated RVH in vivo. In in vitro studies, succinate stimulated the up-regulation of the hypertrophic gene marker anp. All these effects were inhibited by the antagonist of PI3K, wortmannin, both in vivo and in vitro. Finally, we found that the GPR91-PI3K/Akt axis was also up-regulated compared with the sham in human RVH. Conclusions: Our results suggest that succinate-GPR91 is involved in RVH via PI3K/Akt signaling in vivo and in vitro. GPR91 may be a novel therapeutic target for RVH induced by pressure overload.

Thymosin Beta 4 Protects Mice from Monocrotaline-Induced Pulmonary Hypertension and Right Ventricular Hypertrophy

Wei, Chuanyu; Kim, Il-Kwon; Li, Li; Wu, Liling; Gupta, Sudhiranjan
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Publicado em 20/11/2014 EN
Relevância na Pesquisa
66.17%
Pulmonary hypertension (PH) is a progressive vascular disease of pulmonary arteries that impedes ejection of blood by the right ventricle. As a result there is an increase in pulmonary vascular resistance and pulmonary arterial pressure causing right ventricular hypertrophy (RVH) and RV failure. The pathology of PAH involves vascular cell remodeling including pulmonary arterial endothelial cell (PAEC) dysfunction and pulmonary arterial smooth muscle cell (PASMC) proliferation. Current therapies are limited to reverse the vascular remodeling. Investigating a key molecule is required for development of new therapeutic intervention. Thymosin beta-4 (Tβ4) is a ubiquitous G-actin sequestering protein with diverse biological function and promotes wound healing and modulates inflammatory responses. However, it remains unknown whether Tβ4 has any protective role in PH. The purpose of this study is to evaluate the whether Tβ4 can be used as a vascular-protective agent. In monocrotaline (MCT)-induced PH mouse model, we showed that mice treated with Tβ4 significantly attenuated the systolic pressure and RVH, compared to the MCT treated mice. Our data revealed for the first time that Tβ4 selectively targets Notch3-Col 3A-CTGF gene axis in preventing MCT-induced PH and RVH. Our study may provide pre-clinical evidence for Tβ4 and may consider as vasculo-protective agent for the treatment of PH induced RVH.

Modulation of Oxytocin Receptors in Right Ventricular Hypertrophy

Wang, Yang
Fonte: Université de Montréal Publicador: Université de Montréal
Tipo: Thèse ou Mémoire numérique / Electronic Thesis or Dissertation
EN
Relevância na Pesquisa
96.39%
L’hypertension pulmonaire (HP) est une maladie dont l’étiologie est inconnue et qui entraîne ultimement une défaillance du ventricule droit (VD) et le décès. L’HP peut être induite chez le rat par la la monocrotaline (MCT), un alcaloïde pyrrolizidique extrait de la plante Crotalaria Spectabilis, causant des lésions à l’endothélium des artères pulmonaires, menant à un épaississement de ces dernières et à une augmentation de la résistance vasculaire. Ceci à pour conséquence de causer une hypertrophie du VD, de l’inflammation, une dysfonction endothéliale NO-dépendante des artères coronariennes et une augmentation des peptides natriurétiques circulants. Objectif: Nous avons testé l’hypothèse selon laquelle l’étiopathologie de l’HP impliquerait le récepteur à ocytocine (OTR) dû à son implication fonctionnelle avec les cytokines inflammatoires et la libération du peptide natriurétique atrial (ANP) et du NO. Méthodes: Des rats mâles Sprague-Dawley pesant 220-250g reçurent une seule injection sous-cutanée de MCT (60 mg/kg). 6 à 7 semaines (46±1 jours) suivant l’injection, les rats furent sacrifiés et l’expression génique et protéique fut déterminée par PCR en temps réel et par western blot...