Pulmonary artery banding is a relevant model to study the right ventricular remodeling and dysfunction that occurs in pulmonary arterial hypertension

2020 ◽  
Vol 129 (2) ◽  
pp. 238-246 ◽  
Author(s):  
Yohei Akazawa ◽  
Kenichi Okumura ◽  
Ryo Ishii ◽  
Cameron Slorach ◽  
Wei Hui ◽  
...  

Although animal models of pulmonary arterial hypertension and pressure loading are important to study right ventricular (RV) pathophysiology, pulmonary arterial hypertension models cannot interrogate RV responses independent of pulmonary vascular effects. Comparing three commonly used rat models under similar elevated RV pressure, we found that all models resulted in comparable maladaptive RV remodeling and dysfunction. Thus, these findings suggest that the pulmonary artery banding model can be used to investigate mechanisms of RV dysfunction in RV pressure overload and the effect of potential therapies.

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Yijia Xiang ◽  
Changhong Cai ◽  
Yonghui Wu ◽  
Lebing Yang ◽  
Shiyong Ye ◽  
...  

Background. Pulmonary artery remodeling is important in the development of pulmonary artery hypertension. The TGF-β1/Smads signaling pathway is activated in pulmonary arterial hypertension (PAH) in rats. Icariin (ICA) suppresses the TGF-β1/Smad2 pathway in myocardial fibrosis in rats. Therefore, we investigated the role of icariin in PAH by inhibiting the TGF-β1/Smads pathway. Methods. Rats were randomly divided into control, monocrotaline (MCT), MCT + ICA-low, and MCT + ICA-high groups. MCT (60 mg/kg) was subcutaneously injected to induce PAH, and icariin (50 or 100 mg/kg.d) was orally administered for 2 weeks. At the end of the fourth week, right ventricular systolic pressure (RVSP) was obtained and the right ventricular hypertrophy index (RI) was determined as the ratio of the right ventricular weight to the left ventricular plus septal weight (RV/LV + S). Western blots were used to determine the expression of TGF-β1, Smad2/3, P-Smad2/3, and matrix metalloproteinase-2 (MMP2) in lung tissues. Results. Compared to the control group, RVSP and RI were increased in the MCT group (ρ < 0.05). Additionally, TGF-β1, Smad2/3, P-Smad2/3, and MMP2 expressions were obviously increased (ρ < 0.01). Compared to the MCT group, RVSP and RI were decreased in the MCT + ICA group (ρ < 0.05). TGF-β1, Smad2/3, P-Smad2/3, and MMP2 expressions were also inhibited in the icariin treatment groups (ρ < 0.05). Conclusions. Icariin may suppress MCT-induced PAH via the inhibition of the TGFβ1-Smad2/3 pathway.


2021 ◽  
Vol 22 (Supplement_1) ◽  
Author(s):  
M Suzuki ◽  
Y Tanaka ◽  
K Yamashita ◽  
A Shono ◽  
K Sumimoto ◽  
...  

Abstract Funding Acknowledgements Type of funding sources: None. Background The haemodynamic effect of atrial septal defect (ASD) is a chronic volume overload of the right heart and pulmonary vasculature. Pulmonary overcirculation is generally compensated for by the right ventricular (RV) and pulmonary arterial (PA) reserve. However, in a subset of patients, prolonged pulmonary overcirculation insidiously induces obstructive pulmonary vasculopathy, which results in postoperative residual pulmonary arterial hypertension (PAH) after ASD closure. Postoperative PAH is a major concern because it is closely associated with poor outcomes and impaired quality of life. However, to date, no clinically robust predictors of postoperative residual PAH have been clearly identified. Purpose This study sought to assess the haemodynamic characteristics of ASD patients in terms of mechano-energetic parameters and to identify the predictors of postoperative residual PAH in these patients. Methods A total of 120 ASD patients (age: 58 ± 17 years) and 46 normal controls were recruited. As previously reported, the simplified RV contraction pressure index (sRVCPI) was calculated as an index of RV external work by multiplying the tricuspid annular plane systolic excursion (TAPSE) by the pressure gradient between the RV and right atrium. RV- PA coupling was evaluated using TAPSE divided by PA systolic pressure as an index of the RV length-force relationship. These parameters were measured both at baseline and 6 months after ASD closure. Results As expected, baseline sRVCPI was significantly greater in patients with ASD than in controls (775 ± 298 vs. 335 ± 180 mm Hg • mm, P &lt; 0.01), which indicated significant "RV overwork". As a result, RV-PA coupling in ASD patients was significantly impaired compared to that in controls (0.9 ± 0.8 vs. 3.5 ± 1.7 mm/mm Hg, P &lt; 0.01). All 120 ASD patients underwent transcatheter or surgical shunt closure; 15 of them had residual PAH after closure. After 6 months, RV-PA coupling index significantly improved in patients without residual PAH, from 0.96 ± 0.81 to 1.27 ± 1.24 mm/mm Hg (P = 0.02). Furthermore, RV load was markedly reduced, with sRVCPI falling from 691 ± 258 to 434 ± 217 mm Hg • mm, P &lt; 0.01). However, in patients with residual PAH, RV-PA coupling index deteriorated from 0.64 ± 0.23 to 0.53 ± 0.12 mm/mm Hg (P &lt; 0.01). As a result, RV overload was not significantly relieved (sRVCPI; from 971 ± 382 to 783 ± 166 mm Hg • mm, P = 0.22). In a multivariate analysis, baseline pulmonary vascular resistance (hazard ratio 1.009; P &lt; 0.01) and preoperative sRVPCI (hazard ratio 1.003; P &lt; 0.01) revealed to be independent predictors of residual PAH. Conclusion In terms of mechano-energetic function, preoperative "RV overwork" can be used as a robust predictor of an impaired RV-PA relationship in ASD patients. Moreover, periodic assessment of sRVPCI may contribute to the better management for patients with unrepaired ASD. Abstract Figure.


Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Allan K Alencar ◽  
Sharlene L Pereira ◽  
Arthur E Kummerle ◽  
Sharon S Langraf ◽  
Celso Caruso-Neves ◽  
...  

Pulmonary arterial hypertension (PAH) is characterized by enhanced pulmonary vascular resistance with subsequent remodeling and right ventricular hypertrophy. Vascular reactivity and ventricular function were investigated in rats with monocrotaline-induced PAH and treated with a new N-acylhydrazone derivative named as LASSBio-1359. METHODS: 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 monocrotaline (MCT) (60 mg/kg) for PAH induction and were randomly divided in groups which were treated with: saline, vehicle and LASSBio-1359 (50 mg/kg p.o.). After 14 days of treatment, some parameters were evaluated: pulmonary acceleration time (PAT); right ventricular systolic pressure (RVSP); vascular reactivity to acetylcholine; expression of iNOS in pulmonary tissue; wall thickness of pulmonary artery (PAWT). Results: PAT (ms) was increased from 26.2 ± 2.8 to 41.3 ± 3.9 in PAH group treated with vehicle (n=8, p<0.05) and was reduced to 24.2 ± 1.7 when PAH group was treated with LASSBio-1359. RVSP (mmHg) increased from 26.0 ± 2.0 to 55.2 ± 2.3 in PAH group (p<0.05) but was similar to control after treatment with LASSBio-1359 (31.8 ± 2.3 mm Hg). Ratio of right ventricle and body weight (mg/g) was 0.66 ± 0.02, 1.63 ± 0.16 and 0.87 ± 0.10 for control, vehicle- and LASSBio-1359-treated PAH groups, respectively. PAH promoted ventricular dysfunction which was reduced by LASSBio-1359. The pulmonary artery maximum relaxation (%) was 57.3 ± 5.5, 43.6 ± 1.2 and 61.4 ± 8.4 for control, vehicle and LASSBio-1359-treated groups indicating that PAH promoted endothelium injury which was recovered by LASSBio-1359. iNOS expression in pulmonary tissue was increased from 0.48 ± 1.31 to 0.98 ± 3.14 in PAH group and reduced to 0.53 ± 1.83 in rats treated with LASSBio-1359. The PAWT (%) were increased from 74.1 ± 1.3 to 90.2 ± 2.7 in PAH group (p<0.05) but was 74.4 ± 1.3 when treated with LASSBio-1359. This compound showed an in vitro vasodilatory activity mediated by activation of adenosinergic A2A receptor. Conclusion: LASSBio-1359 reduced ventricular and vascular dysfunction in monocrotaline-induced PAH in rats indicating a possible new alternative to treat PAH.


2020 ◽  
Author(s):  
Song Jiyang ◽  
Wan Nan ◽  
Shen Shutong ◽  
Wei Ying ◽  
Cao Yunshan

Abstract Background: Right ventricular (RV) failure induced by sustained pressure overload is a major contributor to morbidity and mortality in several cardiopulmonary disorders. Reliable and reproducible animal models of RV failure are important in order to investigate disease mechanisms and effects of potential therapeutic strategies. To establish a rat model of RV failure perfectly, we observed the right ventricle and carotid artery hemodynamics characteristics in different degrees of pulmonary artery banding of rats of different body weights. Methods: Rats were subjected to 6 groups:control(0%, n=5)(pulmonary arterial banding 0%), PAB(1-30%, n=4)(pulmonary arterial banding1-30%), PAB(31-60%, n=6)(pulmonary arterial banding31-60%),PAB(61-70%, n=5)(pulmonary arterial bandin61-70%), PAB(71-80%,n=4)(pulmonary arterial banding71-80%), PAB(100%, n=3)(pulmonary arterial banding 100%). We measured the right ventricular pressure(RVP) by right heart catheterization when the pulmonary arterial was ligated. Results: The RVP gradually increased with increasing degree of banding, but when occlusion level exceeding 70%, high pressure state can be only maintained for a few minutes or seconds, and then the RVP drops rapidly until it falls below the normal pressure, which in Group F particularly evident.Conclusions: RVP have different reactions when the occlusion level is not the same, and the extent of more than 70% ligation is a successful model of acute right heart failure. These results may have important consequences for therapeutic strategies to prevent acute right heart failure.


Pulmonology ◽  
2019 ◽  
Vol 25 (4) ◽  
pp. 248-251
Author(s):  
S. Hoette ◽  
N. Creuzé ◽  
C.E. Rochitte ◽  
G. Simonneau ◽  
M. Humbert ◽  
...  

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