scholarly journals Congestive Hepatopathy Secondary to Right Ventricular Hypertrophy Related to Monocrotaline-Induced Pulmonary Arterial Hypertension

2021 ◽  
Vol 22 (21) ◽  
pp. 11891
Author(s):  
Douglas Mesadri Gewehr ◽  
Allan Fernando Giovanini ◽  
Beatriz Alvarez Mattar ◽  
Anelyse Pulner Agulham ◽  
Andressa de Souza Bertoldi ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Right Ventricular ◽  
Rat Model ◽  
Ventricular Hypertrophy ◽  
Right Ventricular Hypertrophy ◽  
Histological Evaluation ◽  
Hepatic Atrophy ◽  
Pulmonary Arterial ◽  
Congestive Hepatopathy

Heart dysfunction and liver disease often coexist. Among the types of cardiohepatic syndrome, Type 2 is characterized by the chronic impairment of cardiac function, leading to chronic liver injury, referred to as congestive hepatopathy (CH). In this study, we aimed to establish a rat model of CH secondary to right ventricular hypertrophy (RVH) related to monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH). Fifty male Wistar rats were divided into four groups and randomly assigned to control and experimental groups. Three experimental groups were submitted to intraperitoneal MCT inoculation (60 mg/kg) and were under its effect for 15, 30 and 37 days. The animals were then sacrificed, obtaining cardiac and hepatic tissues for anatomopathological and morphometric analysis. At macroscopic examination, the livers in the MCT groups presented a nutmeg-like appearance. PAH produced marked RVH and dilatation in the MCT groups, characterized by a significant increase in right ventricular free wall thickness (RVFWT) and chamber area. At histological evaluation, centrilobular congestion was the earliest manifestation, with preservation of the hepatocytes. Centrilobular hemorrhagic necrosis was observed in the groups exposed to prolonged MCT. Sinusoidal dilatation was markedly increased in the MCT groups, quantified by the Sinusoidal Lumen Ratio (SLR). The Congestive Hepatic Fibrosis Score and the Centrilobular Fibrosis Ratio (CFR) were also significantly increased in the MCT30 group. Hepatic atrophy, steatosis, apoptotic bodies and, rarely, hydropic swelling were also observed. SLR correlated strongly with CFR and RVFWT, and CFR correlated moderately with RVFWT. Our rat model was able to cause CH, related to monocrotaline-induced PAH and RVH; it was feasible, reproducible, and safe.

Abstract 058: Novel Agonist of Adenosine Receptor Ameliorates Ventricular and Vascular Dysfunction in Monocrotaline-induced Pulmonary Arterial Hypertension in Rats

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Gisele Zapata-Sudo ◽  
Allan K Alencar ◽  
Sharlene L Pereira ◽  
Emanelle Ferraz ◽  
José H Nascimento ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Right Ventricular ◽  
Wall Thickness ◽  
Adenosine Receptor ◽  
Ventricular Hypertrophy ◽  
Systolic Pressure ◽  
Right Ventricular Hypertrophy ◽  
A2a Adenosine Receptors ◽  
Pulmonary Arterial

Aims: Pulmonary arterial hypertension (PAH) consists of increased pulmonary vascular resistance and remodeling and right ventricular hypertrophy. This work investigated the effects of a new N -acylhydrazone derivative, (E)-N’-(3,4-dimethoxybenzylidene)-4-methoxybenzohydrazide (LASSBio-1386), in rats with monocrotaline (MCT)-induced PAH. Methods and Results: Protocols were approved by Animal Care and Use Committee at Universidade Federal do Rio de Janeiro. Male Wistar rats received a single i.p. injection of MCT (60 mg/kg) for PAH induction. Experimental groups were: control, MCT + vehicle (DMSO), MCT + LASSBio-1386 (50 mg/kg p.o.). The animals were treated with vehicle or LASSBio-1386 for 14 days after the onset of disease (n = 6). Right ventricular systolic pressure (RVSP) and relation between RV weight to body weight (RV/BW) were analyzed. Transthoracic echocardiography was performed to determine pulmonary acceleration time (PAT), pulmonary artery diameter and RV wall thickness. Pulmonary vascular morphometry was analyzed using images of terminal arterioles and wall thickness was measured. The parameters evaluated are shown in table 1. In addition, LASSBio-1386-induced vasorelaxation was mediated partially by the activation of A2A adenosine receptors, with an IC50 of 6.2 ± 1.2 µM. Docking analysis in the A 2A crystal structure was performed using the program GOLD 5.1 and showed the interaction of the compound with A 2A receptor. Conclusions: LASSBio-1386 effectively reversed right ventricular hypertrophy and pulmonary vascular remodeling in rats with MCT-induced PAH through activation of adenosine receptor.

Astragalus Polysaccharides Attenuate Monocrotaline-Induced Pulmonary Arterial Hypertension in Rats

2017 ◽  
Vol 45 (04) ◽  
pp. 773-789 ◽  
Author(s):  
Lin-Bo Yuan ◽  
Chun-Yan Hua ◽  
Sheng Gao ◽  
Ya-Ling Yin ◽  
Mao Dai ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Pulmonary Artery ◽  
Arterial Hypertension ◽  
Right Ventricular ◽  
Ventricular Hypertrophy ◽  
Biological Activities ◽  
Right Ventricular Hypertrophy ◽  
Astragalus Polysaccharides ◽  
Pulmonary Hemodynamic ◽  
Pulmonary Arterial

Astragalus polysaccharides (APS) have been shown to possess a variety of biological activities including anti-oxidant and anti-inflammation functions in a number of diseases. However, their function in pulmonary arterial hypertension (PAH) is still unknown. Rats received APS (200[Formula: see text]mg/kg once two days) for 2 weeks after being injected with monocrotaline (MCT; 60[Formula: see text]mg/kg). The pulmonary hemodynamic index, right ventricular hypertrophy, and lung morphological features of the rat models were examined, as well as the NO/eNOS ratio of wet lung and dry lung weight and MPO. A qRT-PCR and p-I[Formula: see text]B was used to assess IL-1[Formula: see text], IL-6 and TNF-[Formula: see text] and WB was used to detect the total I[Formula: see text]B. Based on these measurements, it was found that APS reversed the MCT-induced increase in mean pulmonary arterial pressure (mPAP) (from 32.731[Formula: see text]mmHg to 26.707[Formula: see text]mmHg), decreased pulmonary vascular resistance (PVR) (from 289.021[Formula: see text]mmHg[Formula: see text][Formula: see text] min/L to 246.351[Formula: see text]mmHg[Formula: see text][Formula: see text][Formula: see text]min/L), and reduced right ventricular hypertrophy (from 289.021[Formula: see text]mmHg[Formula: see text][Formula: see text][Formula: see text]min/L to 246.351 mmHg[Formula: see text][Formula: see text][Formula: see text]min/L) ([Formula: see text]0.05). In terms of pulmonary artery remodeling, the WT% and WA% decreased with the addition of APS. In addition, it was found that APS promoted the synthesis of eNOS and the secretion of NO, promoting vasodilation and APS decreased the MCT-induced elevation of MPO, IL-1[Formula: see text], IL-6 and TNF-[Formula: see text], reducing inflammation. Furthermore, APS was able to inhibit the activation of pho-I[Formula: see text]B[Formula: see text]. In couclusion, APS ameliorates MCT-induced pulmonary artery hypertension by inhibiting pulmonary arterial remodeling partially via eNOS/NO and NF-[Formula: see text]B signaling pathways.

scholarly journals Pulmonary vascular disease in mice xenografted with human BM progenitors from patients with pulmonary arterial hypertension

Blood ◽  
2012 ◽  
Vol 120 (6) ◽  
pp. 1218-1227 ◽  
Author(s):  
Kewal Asosingh ◽  
Samar Farha ◽  
Alan Lichtin ◽  
Brian Graham ◽  
Deepa George ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Right Ventricular ◽  
Vascular Injury ◽  
Ventricular Hypertrophy ◽  
Right Ventricular Hypertrophy ◽  
Endothelial Injury ◽  
Hematopoietic Stem ◽  
Pulmonary Arterial ◽  
Myeloid Progenitors

Abstract Hematopoietic myeloid progenitors released into the circulation are able to promote vascular remodeling through endothelium activation and injury. Endothelial injury is central to the development of pulmonary arterial hypertension (PAH), a proliferative vasculopathy of the pulmonary circulation, but the origin of vascular injury is unknown. In the present study, mice transplanted with BM-derived CD133+ progenitor cells from patients with PAH, but not from healthy controls, exhibited morbidity and/or death due to features of PAH: in situ thrombi and endothelial injury, angioproliferative remodeling, and right ventricular hypertrophy and failure. Myeloid progenitors from patients with heritable and/or idiopathic PAH all produced disease in xenografted mice. Analyses of hematopoietic transcription factors and colony formation revealed underlying abnormalities of progenitors that skewed differentiation toward the myeloid-erythroid lineage. The results of the present study suggest a causal role for hematopoietic stem cell abnormalities in vascular injury, right ventricular hypertrophy, and morbidity associated with PAH.

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