scholarly journals Decreased Expression of Canstatin in Rat Model of Monocrotaline-Induced Pulmonary Arterial Hypertension: Protective Effect of Canstatin on Right Ventricular Remodeling

2020 ◽  
Vol 21 (18) ◽  
pp. 6797
Author(s):  
Akira Sugiyama ◽  
Maina Kaisho ◽  
Muneyoshi Okada ◽  
Kosuke Otani ◽  
Hideyuki Yamawaki
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Right Ventricular ◽  
Rat Model ◽  
Ventricular Remodeling ◽  
Weight Ratio ◽  
Enzyme Linked Immunosorbent Assay ◽  
Protective Effects ◽  
Ejection Time ◽  
Pulmonary Arterial

Pulmonary arterial hypertension (PAH) is a progressive disease which causes right ventricular (RV) failure. Canstatin, a C-terminal fragment of type IV collagen α2 chain, is expressed in various rat organs. However, the expression level of canstatin in plasma and organs during PAH is still unclear. We aimed to clarify it and further investigated the protective effects of canstatin in a rat model of monocrotaline-induced PAH. Cardiac functions were assessed by echocardiography. Expression levels of canstatin in plasma and organs were evaluated by enzyme-linked immunosorbent assay and Western blotting, respectively. PAH was evaluated by catheterization. RV remodeling was evaluated by histological analyses. Real-time polymerase chain reaction was performed to evaluate RV remodeling-related genes. The plasma concentration of canstatin in PAH rats was decreased, which was correlated with a reduction in acceleration time/ejection time ratio and an increase in RV weight/body weight ratio. The protein expression of canstatin in RV, lung and kidney was decreased in PAH rats. While recombinant canstatin had no effect on PAH, it significantly improved RV remodeling, including hypertrophy and fibrosis, and prevented the increase in RV remodeling-related genes. We demonstrated that plasma canstatin is decreased in PAH rats and that administration of canstatin exerts cardioprotective effects.

Right ventricular longitudinal strain with CMR can more accurately estimate right ventricular functional reserve in rats with pulmonary arterial hypertension

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
H Sato ◽  
Y Someya ◽  
Y Takahashi ◽  
K Kumasaka ◽  
W Sato ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Right Ventricular ◽  
Longitudinal Strain ◽  
Weight Ratio ◽  
Contractile Properties ◽  
Funding Source ◽  
Functional Reserve ◽  
Pulmonary Arterial ◽  
Cmr Imaging

Abstract Background Right ventricular (RV) function is an important prognostic factor in patients with pulmonary arterial hypertension (PAH). Recently, CMR has become an attractive modality for follow up and providing prognosis in the patients, and strain has been used as a newer parameter to assess contractile properties of ventricle. It has not yet been established, however, whether RV strain with CMR can estimate RV functional reserve in the patients with PAH. Purpose We focused on CMR imaging of RV, investigating whether RV longitudinal strain can estimate RV functional reserve using a rat model with PAH. Method Rats were given a subcutaneous injection of 60 mg/kg monocrotaline (MCT-rats) or solvent (Ctr-rats). Four weeks after the injection, 25% of MCT-rats died due to RV failure. In the survivors of MCT- (n=19) and Ctr-rats (n=5), retrospective ECG-gated cine MR (16 phases/beat) was imaged with a 7T scanner. Subsequently, we measured RV pressure (RVP) via right internal jugular vein and dissected trabeculae (length = 1.45±0.07 mm, width = 334±27 μm, thickness = 114±6 μm) from RVs. We calculated weight ratio of RV free wall to left ventricle (LV) by RV/(LV+septum). Trabeculae were electrically stimulated with 2-s stimulus intervals, and force was measured using a silicon strain gauge (0.7 mM extracellular Ca2+, 24°C). To determine contractile properties of RV muscle, dF/dt was calculated. Using CMR imaging, we measured RV ejection fraction (RVEF) and RV longitudinal strain (RVLS). To modulate RVP, we intravenously injected 5 nmol endothelin-1 (ET-1) and again measured RVEF and RVLS. Results MCT-rats showed higher systolic RVP (62.5±16.6 vs. 25.9±1.86 mmHg, p<0.01) and higher weight ratio of RV (0.60±0.03 vs. 0.28±0.02, p<0.05). In CMR imaging, MCT-rats showed lower RVEF (36.1±11.2 vs. 64.8±8.4%, p<0.001) and lower RVLS (−18±9 vs. −30±1%, p<0.05). In trabeculae from RVs, MCT-rats showed lower developed force and lower dF/dt (p<0.01). Correlation between RVLS and dF/dt was higher (n=20, r=0.53, p<0.05) than that between RVEF and dF/dt (r=0.24). In addition, RVLS and dF/dt had already been decreased in 5 MCT-rats with relatively preserved RVEF (>50%), suggesting that RVLS decreases earlier than RVEF in MCT-rats. Ten minutes after the injection of ET-1, RVP was increased from 49.4±7.9 to 57.9±6.4 mmHg in MCT-rats (n=6). In MCT-rats with preserved RVEF and decreased RVLS, the increase in RVP chiefly decreased RVEF while it did not change RVLS and RVEF in Ctr-rats, meaning that RV functional reserve had been decreased in MCT-rats. In trabeculae, developed force and dF/dt were increased after the addition of 0.1 μM ET-1 in MCT- (n=11, p<0.01) and Ctr-rats (n=4, p<0.01). Conclusion These results suggest that in rats with PAH, RVLS obtained from CMR can estimate RV functional reserve earlier and more accurately than RVEF. Therefore, RV strain with CMR may become an important parameter to assess RV functional reserve in patients with PAH. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Grant-in-Aid for Young Scientists

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.

scholarly journals Pulmonary arterial hypertension: the case for a bioelectronic treatment

2019 ◽  
Vol 5 (1) ◽  
Author(s):  
Despοina Ntiloudi ◽  
Khaled Qanud ◽  
Jacquelyn-Nicole Tomaio ◽  
George Giannakoulas ◽  
Yousef Al-Abed ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Right Ventricular ◽  
Systemic Inflammation ◽  
Ventricular Remodeling ◽  
Sympathetic Tone ◽  
Unknown Etiology ◽  
Bioelectronic Medicine ◽  
Autonomic Reflexes ◽  
Pulmonary Arterial

AbstractPulmonary arterial hypertension (PAH) is a rare disease of unknown etiology that progresses to right ventricular failure. It has a complex pathophysiology, which involves an imbalance between vasoconstrictive and vasodilative processes in the pulmonary circulation, pulmonary vasoconstriction, vascular and right ventricular remodeling, systemic inflammation, and autonomic imbalance, with a reduced parasympathetic and increased sympathetic tone. Current pharmacological treatments for PAH include several classes of drugs that target signaling pathways in vascular biology and cardiovascular physiology, but they can have severe unwanted effects and they do not typically stop the progression of the disease. Pulmonary artery denervation has been tested clinically as a method to suppress sympathetic overactivation, however it is a nonspecific and irreversible intervention. Bioelectronic medicine, in particular vagus nerve stimulation (VNS), has been used in cardiovascular disorders like arrhythmias, heart failure and arterial hypertension and could, in principle, be tested as a treatment in PAH. VNS can produce pulmonary vasodilation and renormalize right ventricular function, via activation of pulmonary and cardiac vagal fibers. It can suppress systemic inflammation, via activation of fibers that innervate the spleen. Finally, VNS can gradually restore the balance between parasympathetic and sympathetic tone by regulating autonomic reflexes. Preclinical studies support the feasibility of using VNS in PAH. However, there are challenges with such an approach, arising from the need to affect a relatively small number of relevant vagal fibers, and the potential for unwanted cardiac and noncardiac effects of VNS in this sensitive patient population.

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