Abstract 2623: Right Ventricular Hypertrophy in Monocrotaline-induced Pulmonary Hypertension is Associated with Impaired Oxidative Metabolism and Action Potential Prolongation

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Lin Piao ◽  
Dalia Urboniene ◽  
Hannah J Zhang ◽  
Peter T Toth ◽  
Jalees Rehman ◽  
...  
Keyword(s):  
Pulmonary Artery ◽  
Action Potential ◽  
Right Ventricular ◽  
Ventricular Hypertrophy ◽  
Systolic Pressure ◽  
Right Ventricular Hypertrophy ◽  
Monophasic Action Potential ◽  
Metabolic Shift ◽  
O2 Consumption ◽  
Action Potential Prolongation

Introduction: Right ventricular hypertrophy (RVH) and right ventricular failure are major determinants of prognosis and functional state in pulmonary artery hypertension (PAH). We previously found a mitochondrial metabolic shift in the pulmonary circulation in clinical as well as experimental PAH that includes a shift from oxidation to glycolysis, decreased production of reactive oxygen species (ROS) and normoxic activation of HIF-1α and decreased expression of voltage-gated potassium channels. In this study, we hypothesize that during RVH there is a similar metabolic shift in the RV characterized by impaired mitochondrial respiration and that the resulting electrical remodeling causes action potential prolongation. Methods and Results: PAH was induced in Sprague-Dawley rats by single injection of monocrotaline (60mg/Kg). At 3 weeks, PAH was confirmed by a shortened pulmonary artery acceleration time vs controls (13.8±0.7 vs 36.2±0.2 msec, P < 0.001) as determined by Doppler Echo. RVH was also evident, with a thicker right ventricular free wall in monocrotaline vs control hearts (1.3±0.1 vs 0.9±0.0 mm, P < 0.001 vs control) as assessed by two-dimensional and M-mode Echo. Oxygen consumption of right ventricular tissues (140mg samples) was measured using high-resolution respirometry. In an RV Langendorff model, RV systolic pressure (RVSP) and RV monophasic action potential duration (MAP) were measured. The ratio of RV/LV+S weight increased to 2 fold with monocrotaline (P < 0.001). RVSP in MCT group was increased to 50.9±10.6 vs 21.3±2.7 mmHg, P < 0.05). RV O2-consumption in RVH was significantly reduced vs control [144.1±37.6 vs 277.0±27.4 pmol/(sec*ml), P < 0.05]. The duration of 90% and 75% repolarization of MAP (MAPD90 and MAPD75) was markedly prolonged in RVH (145% and 136% vs controls; P < 0.001, P < 0.05, respectively). Importantly, MAPD90 increased in direct proportion to the severity of PAH, as measured by RVSP. Conclusions: RVH was associated with impaired RV metabolism as evidenced by reduced O2 consumption. This metabolic shift was associated with significant action potential prolongation in the RV. The consequences of this ionic remodeling for arrhythmogenisis and contractility remain to be determined.

scholarly journals Magnesium Sulfate Mitigates the Progression of Monocrotaline Pulmonary Hypertension in Rats

2019 ◽  
Vol 20 (18) ◽  
pp. 4622 ◽  
Author(s):  
Chao-Yuan Chang ◽  
Hung-Jen Shih ◽  
I-Tao Huang ◽  
Pei-Shan Tsai ◽  
Kung-Yen Chen ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Pulmonary Artery ◽  
Right Ventricular ◽  
Magnesium Sulfate ◽  
Ventricular Hypertrophy ◽  
Systolic Pressure ◽  
Right Ventricular Hypertrophy ◽  
Male Rats ◽  
Wall Thickening ◽  
Artery Wall

We investigated whether magnesium sulfate (MgSO4) mitigated pulmonary hypertension progression in rats. Pulmonary hypertension was induced by a single intraperitoneal injection of monocrotaline (60 mg/kg). MgSO4 (100 mg/kg) was intraperitoneally administered daily for 3 weeks, from the seventh day after monocrotaline injection. Adult male rats were randomized into monocrotaline (MCT) or monocrotaline plus MgSO4 (MM) groups (n = 15 per group); control groups were maintained simultaneously. For analysis, surviving rats were euthanized on the 28th day after receiving monocrotaline. The survival rate was higher in the MM group than in the MCT group (100% versus 73.3%, p = 0.043). Levels of pulmonary artery wall thickening, α-smooth muscle actin upregulation, right ventricular systolic pressure increase, and right ventricular hypertrophy were lower in the MM group than in the MCT group (all p < 0.05). Levels of lipid peroxidation, mitochondrial injury, inflammasomes and cytokine upregulation, and apoptosis in the lungs and right ventricle were lower in the MM group than in the MCT group (all p < 0.05). Notably, the mitigation effects of MgSO4 on pulmonary artery wall thickening and right ventricular hypertrophy were counteracted by exogenous calcium chloride. In conclusion, MgSO4 mitigates pulmonary hypertension progression, possibly by antagonizing calcium.

scholarly journals The protective of baicalin on pulmonary hypertension vascular remodeling through regulation of TNF-α signaling pathway

2020 ◽  
Author(s):  
Xia Xue ◽  
Wen Jiang ◽  
Chao Sun ◽  
Jue Wang ◽  
Qian Xin ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Pulmonary Artery ◽  
Right Ventricular ◽  
Signaling Pathway ◽  
Vascular Remodeling ◽  
Ventricular Hypertrophy ◽  
Systolic Pressure ◽  
Right Ventricular Hypertrophy ◽  
Intragastric Administration ◽  
Tnf Α

Abstract Background: Pulmonary hypertension (PH) is a life-threatening disease, so far no effective method for it. Baicalin can attenuate pulmonary artery pressure and reduce right ventricular hypertrophy in PH, however, the potential mechanism remains unexplored. Therefore, the main aim of the present study was to investigate the protective effect and of baicalin on experimental PH vascular remodeling, and reveal the underlying mechanism.Methods: Monocrotaline (MCT)-induced PH rats models was established, and baicalin was given by intragastric administration. Six weeks later, right ventricular systolic pressure (RVSP) and right ventricular hypertrophy index (RVHI) were recorded, lung tissue hematoxylin-eosin (H&E) staining was analysis to reveal the effect of baicalin on MCT-induced PH. In Vitro, we established TNF-α induced pulmonary artery smooth muscle cells (PASMCs) to detect the inhibition of baicalin on vascular remodeling. Furthermore, quantitative real-time polymerase chain reaction (qRT-PCR), western blot and immunofluorescence were used to detect the mRNA and protein expressions.Results: Our results indicated that baicalin could significantly attenuate MCT induced the RVSP and the right ventricular hypertrophy index (RVHI); inhibit pulmonary vascular remodeling and lung fibrosis. Moreover, our results showed baicalin could significantly decrease the expression of inflammatory cytokines, but increase the protein expression of bone morphogenetic protein type II receptor (BMPR2), ID1 and Smad1//5/8.Conclusion:Taken together, our present study confirmed the mechanism of baicalin against PH was associated with inhibition of TNF-α signaling pathway.

Effect of right ventricular hypertrophy on infundibular pressure gradients in dogs

1965 ◽  
Vol 209 (3) ◽  
pp. 513-518
Author(s):  
Peter E. Blundell ◽  
John R. Tobin ◽  
H. J. C. Swan
Keyword(s):  
Pulmonary Artery ◽  
Pressure Gradient ◽  
Right Ventricular ◽  
Arteriovenous Fistula ◽  
Ventricular Hypertrophy ◽  
Pressure Overload ◽  
Volume Overload ◽  
Right Ventricular Hypertrophy ◽  
Pulmonary Artery Banding ◽  
Pressure Gradients

Right ventricular hypertrophy was produced in normal dogs: in six by means of pressure overload (pulmonary artery banding) and in six by means of volume overload (systemic arteriovenous fistula). A greater degree of hypertrophy resulted from the latter procedure. Right ventricular hypertrophy due to chronic pressure overload causes a greater degree of infundibular constriction and much higher pressure gradient than in normal animals or in animals with volume overload. Infundibular pressure gradients associated with severe hypertrophy due to volume overload are not significantly greater than those observed in normal dogs. Infundibular gradients are dominantly related to narrowing of the outflow tract.

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.

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