scholarly journals Pneumonectomy combined with SU5416 induces severe pulmonary hypertension in rats

2016 ◽  
Vol 310 (11) ◽  
pp. L1088-L1097 ◽  
Author(s):  
C. M. Happé ◽  
M. A. de Raaf ◽  
N. Rol ◽  
I. Schalij ◽  
A. Vonk-Noordegraaf ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Systolic Pressure ◽  
Endothelial Cell Proliferation ◽  
Pulmonary Vasculature ◽  
Hypoxic Exposure ◽  
Sprague Dawley ◽  
Pulmonary Arterial ◽  
Severe Pulmonary Arterial Hypertension

The SU5416 + hypoxia (SuHx) rat model is a commonly used model of severe pulmonary arterial hypertension. While it is known that exposure to hypoxia can be replaced by another type of hit (e.g., ovalbumin sensitization) it is unknown whether abnormal pulmonary blood flow (PBF), which has long been known to invoke pathological changes in the pulmonary vasculature, can replace the hypoxic exposure. Here we studied if a combination of SU5416 administration combined with pneumonectomy (PNx), to induce abnormal PBF in the contralateral lung, is sufficient to induce severe pulmonary arterial hypertension (PAH) in rats. Sprague Dawley rats were subjected to SuPNx protocol (SU5416 + combined with left pneumonectomy) or standard SuHx protocol, and comparisons between models were made at week 2 and 6 postinitiation. Both SuHx and SuPNx models displayed extensive obliterative vascular remodeling leading to an increased right ventricular systolic pressure at week 6. Similar inflammatory response in the lung vasculature of both models was observed alongside increased endothelial cell proliferation and apoptosis. This study describes the SuPNx model, which features severe PAH at 6 wk and could serve as an alternative to the SuHx model. Our study, together with previous studies on experimental models of pulmonary hypertension, shows that the typical histopathological findings of PAH, including obliterative lesions, inflammation, increased cell turnover, and ongoing apoptosis, represent a final common pathway of a disease that can evolve as a consequence of a variety of insults to the lung vasculature.

scholarly journals Pulmonary hypertension. Clarifying concepts

ANALES RANM ◽  
2021 ◽  
Vol 138 (138(02)) ◽  
pp. 137-142
Author(s):  
J.R. de Berrazueta Fernández
Keyword(s):  
Pulmonary Hypertension ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Structural Changes ◽  
Systolic Pressure ◽  
Pulmonary Artery Systolic Pressure ◽  
Current Classification ◽  
Mean Pressure ◽  
Pulmonary Arterial ◽  
The Difference

Pulmonary Arterial Hypertension is a central syndrome produced by a large number of cardiological, pulmonary, and systemic diseases that affect the lung bed. It is defined by the existence of a pulmonary artery systolic pressure greater than 30 or a mean pressure greater than 25 mmHg. This definition criterion has been maintained for more than 60 years. However, the current classification includes two concepts: a Pulmonary Arterial Hypertension (PAH) with two groups of disorders in which only pulmonary arterial resistance increases and five groups that are classified as Pulmonary Hypertension (PH): PH Secondary to Pulmonary Veno-occlusive Disease , HP secondary to diseases of the left side of the heart; HP Obliterative diseases and pulmonary hypoxemia; HP Pulmonary thrombus occlusive diseases, and a group of multifactorial HP. The difference is found in how the different diseases affect the pulmonary vascular bed, and how they alter the physiology or behavior of pulmonary resistance, which are the concepts that must be handled when talking about this syndrome and whose structural changes and management we will discuss in a later article.

scholarly journals Chronic thromboembolic pulmonary hypertension: a distinct disease entity

2015 ◽  
Vol 24 (136) ◽  
pp. 246-252 ◽  
Author(s):  
Irene Lang
Keyword(s):  
Pulmonary Hypertension ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Chronic Thromboembolic Pulmonary Hypertension ◽  
Right Heart Failure ◽  
Pulmonary Vasculature ◽  
Distinct Disease ◽  
Thromboembolic Pulmonary Hypertension ◽  
Perfusion Scan ◽  
Pulmonary Arterial

Chronic thromboembolic pulmonary hypertension (CTEPH) is a distinct subtype of pulmonary hypertension (PH). One disease hypothesis is that CTEPH results from the non-resolution of venous thromboembolism. CTEPH is characterised by the presence of obstructive fibrotic thromboembolic material in the major pulmonary vessels, with concomitant microvascular arteriopathy, resulting in progressive PH. The clinical presentation of CTEPH is similar to pulmonary arterial hypertension with nonspecific symptoms, but it is distinguished from pulmonary arterial hypertension by the presence of mismatched segmental defects on the ventilation/perfusion scan. The exact prevalence and incidence of CTEPH are unknown, but are thought to have been underestimated in the past. CTEPH is unique among the subgroups of PH in that it is potentially curable with pulmonary endarterectomy, a surgical intervention intended to remove the occlusive material from the pulmonary vasculature. However, in some patients the obstructions are technically inaccessible or the risk/benefit ratios are unfavourable, making the condition inoperable. It is thought that the involvement of the smaller, more distal vessels is a target for medical treatment. Untreated, CTEPH may result in right heart failure and death. The pathophysiological mechanisms which cause CTEPH are complex and have not yet been fully elucidated.

scholarly journals The Effects of Dexmedetomidine Prescription in Paediatric Patients With Pulmonary Hypertension Under Congenital Heart Surgery

2020 ◽  
Author(s):  
Bahram Ghasemzadeh ◽  
Bahador Azizi ◽  
Simin Azemati ◽  
Mostafa Bagherinasab
Keyword(s):  
Blood Pressure ◽  
Pulmonary Hypertension ◽  
Pulmonary Arterial Hypertension ◽  
Pulmonary Artery ◽  
Arterial Hypertension ◽  
Systolic Blood Pressure ◽  
Systolic Pressure ◽  
Pulmonary Artery Systolic Pressure ◽  
Anesthetic Care ◽  
Pulmonary Arterial

Anesthetized patient management for pediatric patients with pulmonary arterial hypertension (PAH) is a major challenge. The aim of this study was to evaluate the ability of dexmedetomidine to reduce pulmonary arterial hypertension in patients with pulmonary arterial hypertension undergoing cardiac surgery. Sixty-six patients with pulmonary arterial hypertension underwent the study. Patients were randomly divided into two groups: group D received a dexmedetomidine injection in a dose of 1 μg/kg in the first hour and then decreased to 0.5 μg/kg/hr, injection continued after surgery until extubation in the post-anesthetic care unit (PACU). Group C received normal saline 0.9% in a similar volume. Pulmonary artery systolic pressure (PASP) and systemic systolic blood pressure (SSBP) were recorded during and after the surgery in the postanesthetic care unit. Needing vasodilators, sedatives, extubation time, and the length of ICU stay were recorded for all patients. Patients in the dexmedetomidine group showed a significant reduction in Pulmonary artery systolic pressure and Pulmonary artery systolic pressure/systemic systolic blood pressure rates during surgery and during the first 24 hours in the post-anesthetic care unit (P<0.001). The dexmedetomidine group, in comparison with the control group, needed a significantly lower dose of a vasodilator (P<0.001) and a lower dose of sedation (P<0.001). It is concluded that the use of dexmedetomidine during the surgery in children with pulmonary hypertension reduces pulmonary artery systolic pressure during and after the surgery.

Abstract 13972: Dexmedetomidine Ameliorates Monocrotaline Induced Pulmonary Arterial Hypertension in Rats

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Yusuke Kajikawa ◽  
Susumu Hosokawa ◽  
Kenji Wakabayashi ◽  
Yasuhiro Maejima ◽  
Mitsuaki Isobe ◽  
...  
Keyword(s):  
Survival Rate ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Inflammatory Responses ◽  
Systolic Pressure ◽  
Sprague Dawley ◽  
Apoptosis Resistance ◽  
Ventricular Systolic Pressure ◽  
Significant Difference ◽  
Pulmonary Arterial

[Introduction] Pulmonary arterial hypertension (PAH) is characterized by increased proliferation and apoptosis resistance of pulmonary arterial smooth muscle cells (PASMCs). Dexmedetomidine (DEX) is a selective α2-aderenergic receptor agonist that is used for sedation in clinical practice. It has been reported that DEX inhibits inflammatory responses through cytokines, such as TNF-alpha, IL-6. Furthermore other reports show that G-protein-coupled receptors (GPCRs) are regulated by β-arrestins, which are also involved with inflammation. [Hypothesis] DEX ameliorates monocrotaline (MCT)-induced PAH in rats by its anti-inflammatory effect. [Methods] We treated 6 weeks-old male Sprague-Dawley rats with a single 60mg/kg intraperitoneal injection of MCT. After 14 days of injection, one group of rats was started to administer dexmedetomidine (dose: 2μg/kg/hour, MCT+DEX group) continuously using osmotic pumps, the other group was not treated with DEX (MCT group). We performed physiological examination and cardiac catheterization to measure right ventricular systolic pressure (RVSP) at day 23. [Results] Both RVSP and survival rate of rats in MCT+DEX group markedly improved compared with those in MCT group (RVSP; 38mmHg±11mmHg vs 91mmHg±6mmHg, survival rate; 42% vs 0% at day 30). In histological analysis, DEX reduced the medial hypertrophy of pulmonary arterioles, and decreased phosphorylated-NF-kB p65 (p-p65) positive PASMCs in MCT+DEX group compared with those of MCT group. In addition, DEX suppressed PASMCs proliferation with PCNA staining, and induced apoptosis of PASMCs with TUNEL assay. Then we examined the involvement of β-arrestins in PAH. It showed that βarrestin1 expressions reduced in MCT group compared with that of MCT+DEX group with western blotting and immunohistochemistry. However β-arrestin2 expressions had no significant difference between the two groups. [Conclusions] DEX ameliorates MCT-induced PAH in rats, one of the mechanism of which may be NF-kB inhibition through β-arrestin1. DEX can be a new therapeutic tool for PAH.

scholarly journals Identification of the Novel Variants in Patients With Chronic Thromboembolic Pulmonary Hypertension

2020 ◽  
Vol 9 (21) ◽  
Author(s):  
Nobuhiro Yaoita ◽  
Kimio Satoh ◽  
Taijyu Satoh ◽  
Toru Shimizu ◽  
Sakae Saito ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Chronic Thromboembolic Pulmonary Hypertension ◽  
Pulmonary Vasculature ◽  
Nonsynonymous Variant ◽  
Whole Exome ◽  
Thromboembolic Pulmonary Hypertension ◽  
History Of ◽  
Pulmonary Arterial

Background Although chronic thromboembolic pulmonary hypertension (CTEPH) and acute pulmonary embolism (APE) share some clinical manifestations, a limited proportion of patients with CTEPH have a history of APE. Moreover, in histopathologic studies, it has been revealed that pulmonary vasculature lesions similar to pulmonary arterial hypertension existed in patients with CTEPH. Thus, it remains unknown whether these 3 disorders also share genetic backgrounds. Methods and Results Whole exome screening was performed with DNA isolated from 51 unrelated patients with CTEPH of Japanese ancestry. The frequency of genetic variants associated with pulmonary arterial hypertension or APE in patients with CTEPH was compared with those in the integrative Japanese Genome Variation Database 3.5KJPN. Whole exome screening analysis showed 17 049 nonsynonymous variants in patients with CTEPH. Although we found 6 nonsynonymous variants that are associated with APE in patients with CTEPH, there was no nonsynonymous variant associated with pulmonary arterial hypertension. Patients with CTEPH with a history of APE had nonsynonymous variants of F5 , which encodes factor V. In contrast, patients with CTEPH without a history of APE had a nonsynonymous variant of THBD , which encodes thrombomodulin. Moreover, thrombin‐activatable fibrinolysis inhibitor, which is one of the pathogenic proteins in CTEPH, was significantly more activated in those who had the variants of THBD compared with those without it. Conclusions These results provide the first evidence that patients with CTEPH have some variants associated with APE, regardless of the presence or absence of a history of APE. Furthermore, the variants might be different between patients with CTEPH with and without a history of APE.

scholarly journals Rosuvastatin ameliorates the development of pulmonary arterial hypertension in the transgenic (mRen2)27 rat

2009 ◽  
Vol 297 (3) ◽  
pp. H1128-H1139 ◽  
Author(s):  
Vincent G. DeMarco ◽  
Javad Habibi ◽  
Adam T. Whaley-Connell ◽  
Rebecca I. Schneider ◽  
James R. Sowers ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Proliferation ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
No Synthase ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Pulmonary Arterial

We have recently reported that transgenic (mRen2)27 rats (Ren2 rats) exhibit pulmonary arterial hypertension (PAH), which is, in part, mediated by oxidative stress. Since 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors (statins) exhibit beneficial vascular effects independent of cholesterol synthesis, we hypothesized that rosuvastatin (RSV) treatment ameliorates PAH and pulmonary vascular remodeling in Ren2 rats, in part, by reducing oxidative stress. Six-week-old male Ren2 and Sprague-Dawley rats received RSV (10 mg·kg−1·day−1 ip) or vehicle for 3 wk. After treatment, right ventricular systolic pressure (RVSP) and mean arterial pressure (MAP) were measured. To evaluate treatment effects on pulmonary arteriole remodeling, morphometric analyses were performed to quantitate medial thickening and cell proliferation, whereas whole lung samples were used to quantitate the levels of 3-nitrotyrosine, superoxide, stable nitric oxide (NO) metabolites [nitrates and nitrites (NO x)], and expression of NO synthase isoforms. In the Ren2 rat, RVSP is normal at 5 wk of age, PAH develops between 5 and 7 wk of age, and the elevated pressure is maintained with little variation through 13 wk. At 8 wk of age, left ventricular function and blood gases were normal in the Ren2 rat. Ren2 rats exhibited elevations in medial hypertrophy due to smooth muscle cell proliferation, 3-nitrotyrosine, NO x, NADPH oxidase activity, and endothelial NO synthase expression compared with Sprague-Dawley rats. RSV significantly blunted the increase in RVSP but did not reduce MAP in the Ren2 rat; additionally, RSV significantly attenuated the elevated parameters examined in the Ren2 rat. These data suggest that statins may be a clinically viable adjunct treatment of PAH through reducing peroxynitrite formation.

scholarly journals The Isoquinoline-Sulfonamide Compound H-1337 Attenuates SU5416/Hypoxia-Induced Pulmonary Arterial Hypertension in Rats

Cells ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 66
Author(s):  
Hiroki Shoji ◽  
Yoko Yoshida ◽  
Takayuki Jujo Sanada ◽  
Akira Naito ◽  
Junko Maruyama ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Pulmonary Arterial Hypertension ◽  
Right Ventricle ◽  
Arterial Hypertension ◽  
Vascular Remodeling ◽  
Myosin Light Chain ◽  
Pulmonary Vasculature ◽  
Pulmonary Vascular Remodeling ◽  
Pulmonary Arterial ◽  
Sulfonamide Compound

Pulmonary arterial hypertension (PAH) is characterized by elevated pulmonary arterial pressure and right heart failure. Selective pulmonary vasodilators have improved the prognosis of PAH; however, they are not able to reverse pulmonary vascular remodeling. Therefore, a search for new treatment agents is required. H-1337 is an isoquinoline-sulfonamide compound that inhibits multiple serine/threonine kinases, including Rho-associated protein kinase (ROCK) and mammalian target of rapamycin (mTOR). Here, we investigated the effects of H-1337 on pulmonary hypertension and remodeling in the pulmonary vasculature and right ventricle in experimental PAH induced by SU5416 and hypoxia exposure. H-1337 and H-1337M1 exerted inhibitory effects on ROCK and Akt. H-1337 inhibited the phosphorylation of myosin light chain and mTOR and suppressed the proliferation of smooth muscle cells in vitro. H-1337 treatment also suppressed the phosphorylation of myosin light chain and mTOR in the pulmonary vasculature and decreased right ventricular systolic pressure and the extent of occlusive pulmonary vascular lesions. Furthermore, H-1337 suppressed aggravation of right ventricle hypertrophy. In conclusion, our data demonstrated that inhibition of ROCK and mTOR pathways with H-1337 suppressed the progression of pulmonary vascular remodeling, pulmonary hypertension, and right ventricular remodeling.

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