Ventilatory dysfunction precedes pulmonary vascular changes in monocrotaline-treated rats

1991 ◽  
Vol 70 (2) ◽  
pp. 561-566 ◽  
Author(s):  
Y. L. Lai ◽  
J. W. Olson ◽  
M. N. Gillespie
Keyword(s):  
Pulmonary Hypertension ◽  
Right Ventricular ◽  
Wall Thickness ◽  
Ventricular Hypertrophy ◽  
Right Ventricular Hypertrophy ◽  
Functional Study ◽  
Pulmonary Vasculature ◽  
Pulmonary Vascular Disease ◽  
Alveolar Wall ◽  
Lung Dysfunction

Rats with established monocrotaline (MCT)-induced pulmonary hypertension also exhibit a profound increase in lung resistance (RL) and a decrease in lung compliance. Because airway/lung dysfunction could precede and influence the evolution of MCT-induced pulmonary vascular disease, it is important to establish the temporal relationship between development of pulmonary hypertension and altered ventilatory function in MCT-treated rats. To resolve this issue, we segregated 47 young Sprague-Dawley rats into four groups: control (n = 13), MCT1 (n = 9), MCT2 (n = 11), and MCT3 (n = 14). Each MCT rat received a single subcutaneous injection of MCT (60 mg/kg) 1 MCT1), 2 (MCT2), or 3 (MCT3) wk before the functional study. At 1 wk after MCT, significant increases in RL and alveolar wall thickness were observed, as was a significant decrease in carbon monoxide diffusing capacity (DLCO). Medial thickness of pulmonary arteries (50-100 microns OD) and right ventricular hypertrophy were not observed until 2 and 3 wk post-MCT, respectively. Coincident with the right ventricular hypertrophy at 3 wk post-MCT were decreased DLCO and increased alveolar wall thickness and lung dry weight. Pressure-volume curves of air-filled and saline-filled lungs showed marked rightward shifts during the 1st and 2nd wk after MCT administration and then decreased at the 3rd wk. These data suggest that MCT-induced alterations in airway/lung function preceded those of pulmonary vasculature and, therefore, implicate airway/lung dysfunctions as potentially contributing to the later development of pulmonary vascular abnormalities.

Transient severe isolated right ventricular hypertrophy in neonates

2003 ◽  
Vol 13 (4) ◽  
pp. 384-386 ◽  
Author(s):  
Munesh Tomar ◽  
Sitaraman Radhakrishnan ◽  
Savitri Shrivastava
Keyword(s):  
Pulmonary Hypertension ◽  
Right Ventricular ◽  
Ventricular Function ◽  
Ventricular Hypertrophy ◽  
Pressure Overload ◽  
Posterior Wall ◽  
Right Ventricular Hypertrophy ◽  
Pulmonary Vasculature ◽  
Normal Thickness ◽  
The Right

We report two instances of transient isolated right-sided myocardial hypertrophy in patients with an intact ventricular septum, normal thickness of the posterior wall of the left ventricle, and normal ventricular function, diagnosed by echocardiography on the third day of life. The two neonates, born at 36 and 38 weeks gestation respectively, had perinatal distress. Both were diagnosed as having isolated right ventricular hypertrophy with mild pulmonary hypertension, which disappeared in both cases within 8 weeks without any specific therapy. Though the cause of the ventricular hypertrophy remains unclear, we believe that it is the consequence of remodeling of pulmonary vasculature secondary to acute perinatal distress, resulting in persistent pulmonary hypertension and producing pressure overload on the right ventricle, and hence right ventricular hypertrophy. The finding of early and transient right ventricular hypertrophy, with normal left-sided structures and normal ventricular function, has thus far failed to gain attention in the paediatric cardiologic literature.

scholarly journals The Roles of S100A4 and the EGF/EGFR Signaling Axis in Pulmonary Hypertension with Right Ventricular Hypertrophy

Biology ◽  
2022 ◽  
Vol 11 (1) ◽  
pp. 118
Author(s):  
Maria Laggner ◽  
Philipp Hacker ◽  
Felicitas Oberndorfer ◽  
Jonas Bauer ◽  
Thomas Raunegger ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Right Ventricular ◽  
Ventricular Hypertrophy ◽  
Chronic Thromboembolic Pulmonary Hypertension ◽  
Tissue Expression ◽  
Left Ventricular ◽  
Right Ventricular Hypertrophy ◽  
Pulmonary Vasculature ◽  
Mesenchymal Transition ◽  
Pulmonary Arterial

Pulmonary hypertension (PH) is characterized by increased pulmonary arterial pressure caused by the accumulation of mesenchymal-like cells in the pulmonary vasculature. PH can lead to right ventricular hypertrophy (RVH) and, ultimately, heart failure and death. In PH etiology, endothelial-to-mesenchymal transition (EndMT) has emerged as a critical process governing the conversion of endothelial cells into mesenchymal cells, and S100A4, EGF, and EGFR are implicated in EndMT. However, a potential role of S100A4, EGF, and EGFR in PH has to date not been elucidated. We therefore quantified S100A4, EGF, and EGFR in patients suffering from chronic thromboembolic pulmonary hypertension (CTEPH) and idiopathic pulmonary arterial hypertension (iPAH). To determine specificity for unilateral heart disease, the EndMT biomarker signature was further compared between PH patients presenting with RVH and patients suffering from aortic valve stenosis (AVS) with left ventricular hypertrophy. Reduced S100A4 concentrations were found in CTEPH and iPAH patients with RVH. Systemic EGF was increased in CTEPH but not in iPAH, while AVS patients displayed slightly diminished EGF levels. EGFR was downregulated in all patient groups when compared to healthy controls. Longitudinal data analysis revealed no effect of surgical therapies on EndMT markers. Pulmonary thrombo-endarterectomized samples were devoid of S100A4, while S100A4 tissue expression positively correlated with higher grades of Heath–Edwards histopathological lesions of iPAH-derived lung tissue. Histologically, EGFR was not detectable in CTEPH lungs or in iPAH lesions. Together, our data suggest an intricate role for S100A4 and EGF/EGFR in PH with right heart pathology.

scholarly journals Bosentan attenuates right ventricular hypertrophy and fibrosis in normobaric hypoxia model of pulmonary hypertension

2011 ◽  
Vol 30 (7) ◽  
pp. 827-833 ◽  
Author(s):  
Gaurav Choudhary ◽  
Frederick Troncales ◽  
Douglas Martin ◽  
Elizabeth O. Harrington ◽  
James R. Klinger
Keyword(s):  
Pulmonary Hypertension ◽  
Right Ventricular ◽  
Ventricular Hypertrophy ◽  
Right Ventricular Hypertrophy ◽  
Normobaric Hypoxia

scholarly journals Progressive Development of Pulmonary Hypertension Leading to Right Ventricular Hypertrophy Assessed by Echocardiography in Rats.

2003 ◽  
Vol 52 (4) ◽  
pp. 285-294 ◽  
Author(s):  
Yosuke KATO ◽  
Mitsunori IWASE ◽  
Hiroaki KANAZAWA ◽  
Natsuki KAWATA ◽  
Yukie YOSHIMORI ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Right Ventricular ◽  
Ventricular Hypertrophy ◽  
Right Ventricular Hypertrophy ◽  
Progressive Development

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

PLoS ONE ◽  
2012 ◽  
Vol 7 (12) ◽  
pp. e52522 ◽  
Author(s):  
Noritada Yoshikawa ◽  
Noriaki Shimizu ◽  
Takako Maruyama ◽  
Motoaki Sano ◽  
Tomohiro Matsuhashi ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Right Ventricular ◽  
Ventricular Hypertrophy ◽  
Right Ventricular Hypertrophy

Abstract 15303: Dimethylarginine Dimethylaminohydrolase-1 is Not Involved in Chronic Hypoxic Pulmonary Hypertension and Right Ventricular Hypertrophy in Mice

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Juliane Hannemann ◽  
Antonia Glatzel ◽  
Jonas Hillig ◽  
Julia Zummack ◽  
Rainer H Boeger
Keyword(s):  
Pulmonary Hypertension ◽  
Right Ventricular ◽  
Ventricular Hypertrophy ◽  
Chronic Hypoxia ◽  
Right Ventricular Hypertrophy ◽  
Cardiomyocyte Hypertrophy ◽  
No Production ◽  
Knock Out ◽  
Knock Out Mice ◽  
Adma Concentration

Introduction: Chronic hypoxia causes persistent pulmonary vasoconstriction and leads to pulmonary hypertension and right ventricular hypertrophy. Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of NO synthesis; its level increases in hypoxia concomitantly with reduced activity of dimethylarginine dimethylaminohydrolases (DDAH-1 and DDAH-2), the enzymes metabolizing ADMA. DDAH knockout models may therefore help to understand the pathophysiological roles of this enzyme and its substrate, ADMA, in the development of hypoxia-associated pulmonary hypertension. Hypothesis: We hypothesized that DDAH1 knock-out mice have an attenuated hypoxia-induced elevation of ADMA and reduced right ventricular hypertrophy. Methods: DDAH1 knock-out mice (KO) and their wild-type littermates (WT) were subjected to normoxia (NX) or hypoxia (HX) during 21 days. We measured ADMA concentration in plasma, DDAH1 and DDAH2 expression in the lung, right ventricular hypertrophy by the Fulton index, cardiomyocyte hypertrophy by dystrophin staining of heart tissues, and muscularization of pulmonary arterioles by CD31 and α-actin staining of lung sections. Results: DDAH1 KO mice had higher ADMA concentration than WT under NX (2.31±0.33 μmol/l vs. 1.20±0.17 μmol/l; p < 0.05). ADMA significantly increased in WT-HX (to 1.74±0.86 μmol/l; p < 0.05 vs. normoxia), whilst it did not further increase in KO-HX (2.58±0.58 μmol/l; p = n.s.). This was paralleled by a 38±13% reduction in DDAH1 mRNA but not DDAH2 mRNA expression, and reduced DDAH protein expression. We observed right ventricular hypertrophy under hypoxia in both, WT and KO mice, with no significant differences between both genotypes. Further, cardiomyocyte hypertrophy and pulmonary arteriolar muscularization were significantly increased by hypoxia, but not significantly different between WT and KO mice. Conclusions: We conclude that chronic hypoxia causes an elevation of ADMA, which impairs NO production and leads to endothelial dysfunction and vasoconstriction. Downregulation of DDAH expression and activity may be involved in this; however, knockout of DDAH1 does not modify the pathophysiological changes in remodeling of the pulmonary vasculature and the right ventricle.

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