scholarly journals Pulmonary Pulse Wave Transit Time is Associated with Right Ventricular–Pulmonary Artery Coupling in Pulmonary Arterial Hypertension

2016 ◽  
Vol 6 (4) ◽  
pp. 576-585 ◽  
Author(s):  
Kurt W. Prins ◽  
E. Kenneth Weir ◽  
Stephen L. Archer ◽  
Jeremy Markowitz ◽  
Lauren Rose ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Pulmonary Artery ◽  
Arterial Hypertension ◽  
Right Ventricular ◽  
Transit Time ◽  
Pulse Wave ◽  
Pulmonary Vasculature ◽  
Pulmonary Vascular Disease ◽  
Pulse Wave Transit Time ◽  
Pulmonary Arterial

Pulmonary pulse wave transit time (pPTT), defined as the time for the systolic pressure pulse wave to travel from the pulmonary valve to the pulmonary veins, has been reported to be reduced in pulmonary arterial hypertension (PAH); however, the underlying mechanism of reduced pPTT is unknown. Here, we investigate the hypothesis that abbreviated pPTT in PAH results from impaired right ventricular–pulmonary artery (RV-PA) coupling. We quantified pPTT using pulsed-wave Doppler ultrasound from 10 healthy age- and sex-matched controls and 36 patients with PAH. pPTT was reduced in patients with PAH compared with controls. Univariate analysis revealed the following significant predictors of reduced pPTT: age, right ventricular fractional area change (RV FAC), tricuspid annular plane excursion (TAPSE), pulmonary arterial pressures (PAP), diastolic pulmonary gradient, transpulmonary gradient, pulmonary vascular resistance, and RV-PA coupling (defined as RV FAC/mean PAP or TAPSE/mean PAP). Although the correlations between pPTT and invasive markers of pulmonary vascular disease were modest, RV FAC ( r = 0.64, P < 0.0001), TAPSE ( r = 0.67, P < 0.0001), and RV-PA coupling (RV FAC/mean PAP: r = 0.72, P < 0.0001; TAPSE/mean PAP: r = 0.74, P < 0.0001) had the strongest relationships with pPTT. On multivariable analysis, only RV FAC, TAPSE, and RV-PA coupling were independent predictors of pPTT. We conclude that shortening of pPTT in patients with PAH results from altered RV-PA coupling, probably occurring as a result of reduced pulmonary arterial compliance. Thus, pPTT allows noninvasive determination of the status of both the pulmonary vasculature and the response of the RV in patients with PAH, thereby allowing monitoring of disease progression and regression.

Abstract 532: New Agonist of A2a Receptor Reduces Ventricular and Vascular Dysfunction in Monocrotaline-induced Pulmonary Arterial Hypertension in Rats

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Allan K Alencar ◽  
Sharlene L Pereira ◽  
Arthur E Kummerle ◽  
Sharon S Langraf ◽  
Celso Caruso-Neves ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Pulmonary Artery ◽  
Arterial Hypertension ◽  
Right Ventricular ◽  
Vascular Reactivity ◽  
Vascular Dysfunction ◽  
Systolic Pressure ◽  
Pulmonary Tissue ◽  
A2a Receptor ◽  
Pulmonary Arterial

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.

Abstract 18587: Downregulation of Pulmonary Artery Endothelial Catechol-o-methyltransferase Activity by Aldosterone Increases Norepinephrine Levels in Pulmonary Arterial Hypertension

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Samantha Torquato ◽  
Kiyotake Ishikawa ◽  
Jaume Aguerro ◽  
Bradley A Maron ◽  
Joseph Loscalzo ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Pulmonary Artery ◽  
Arterial Hypertension ◽  
Right Heart Failure ◽  
Therapeutic Interventions ◽  
Pulmonary Vasculature ◽  
Methyltransferase Activity ◽  
Comt Activity ◽  
Pulmonary Arterial

Elevated levels of norepinephrine (NE) occur in pulmonary arterial hypertension (PAH) and are determined, in part, by the activity of catechol- O -methyltransferase (COMT). COMT degrades catecholamines, is negatively regulated by calcium, and is expressed by pulmonary artery endothelial cells (PAEC). As hyperaldosteronism occurs in PAH and aldosterone (ALDO) influences calcium levels, we hypothesized that ALDO decreases COMT activity to increase NE levels in PAH. Accordingly, human PAEC were treated with ALDO (10 -7 mol/L), a level that is achieved clinically in PAH, for up to 72 h. Compared to vehicle-treated PAEC, ALDO decreased COMT activity by 59.2 ± 6.2% (p<0.01) to increase NE levels in the medium (122.4 ± 11.8 vs. 210.7 ± 15.5 pg/mL/mg protein, p<0.01). This occurred as a result of an ALDO-mediated decrease in COMT protein expression by 52.6 ± 9.3% (p<0.01) as well as an increase in intracellular calcium levels (102.9 ± 21.0 vs. 167.7 ± 17.8 nmol/L, p<0.05) to inhibit activity. These effects were abrogated by coincubation with spironolactone. To determine the in vivo relevance of these findings, COMT was examined in the rat monocrotaline model of PAH with confirmed hyperALDO. COMT was decreased (47.6 ± 10.2 %control, p<0.05) in remodeled pulmonary arterioles with a concomitant increase in lung NE levels (432.8 ± 44.5 vs. 899.7 ± 34.2 pg/mL, p<0.01) compared to control rats. In the porcine pulmonary vein banding model of pulmonary hypertension (PH-pigs) with elevated mean pulmonary artery pressure (15[13-15] vs. 35[27-43], p<0.01) and pulmonary vascular resistance (PVR) index (1.97[1.74-2.28] vs. 5.78[2.61-8.75], p <0.05), ALDO levels were also increased (27.1 ± 5.1 vs. 60.8 ± 10.6 pg/mL, p<0.03) in advance of right heart failure as compared to sham controls. PH-pigs demonstrated a 48.3 ± 9.9% (p<0.02) decrease in pulmonary vascular COMT expression and an increase in NE levels (114.6 ± 20.2 vs. 1,622.6 ± 489.2 pg/mL, p<0.02) that correlated positively with ALDO levels (R 2 =0.58, p<0.02). These findings were confirmed in patients with PAH. Together, these data indicate that there is crosstalk in the pulmonary vasculature between ALDO and the sympathetic nervous system to regulate NE levels in PAH, and thus, have implications for therapeutic interventions.

scholarly journals Chronic thromboembolic and pulmonary arterial hypertension share right ventricular and pulmonary artery CMR features

Pulmonology ◽  
2019 ◽  
Vol 25 (4) ◽  
pp. 248-251
Author(s):  
S. Hoette ◽  
N. Creuzé ◽  
C.E. Rochitte ◽  
G. Simonneau ◽  
M. Humbert ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Pulmonary Artery ◽  
Arterial Hypertension ◽  
Right Ventricular ◽  
Pulmonary Arterial

scholarly journals Icariin Attenuates Monocrotaline-Induced Pulmonary Arterial Hypertension via the Inhibition of TGF-β1/Smads Pathway in Rats

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Yijia Xiang ◽  
Changhong Cai ◽  
Yonghui Wu ◽  
Lebing Yang ◽  
Shiyong Ye ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Pulmonary Artery ◽  
Arterial Hypertension ◽  
Right Ventricular ◽  
Left Ventricular ◽  
Matrix Metalloproteinase 2 ◽  
Western Blots ◽  
Pulmonary Arterial ◽  
The Right ◽  
Tgf Β1

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.

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.

Right ventricular free wall pacing improves cardiac pump function in severe pulmonary arterial hypertension: a computer simulation analysis

2009 ◽  
Vol 297 (6) ◽  
pp. H2196-H2205 ◽  
Author(s):  
Joost Lumens ◽  
Theo Arts ◽  
Bernard Broers ◽  
Karin A. Boomars ◽  
Pieter van Paassen ◽  
...  
Keyword(s):  
Computer Simulation ◽  
Pulmonary Arterial Hypertension ◽  
Pulmonary Artery ◽  
Arterial Hypertension ◽  
Right Ventricular ◽  
Left Ventricular ◽  
Free Wall ◽  
Pump Function ◽  
Cardiac Pump Function ◽  
Pulmonary Arterial

In pulmonary arterial hypertension (PAH), duration of myofiber shortening is prolonged in the right ventricular (RV) free wall (RVfw) compared with that in the interventricular septum and left ventricular free wall. This interventricular mechanical asynchrony eventually leads to right heart failure. We investigated by computer simulation whether, in PAH, early RVfw pacing may improve interventricular mechanical synchrony and, hence, cardiac pump function. A mathematical model of the human heart and circulation was used to simulate left ventricular and RV pump mechanics and myofiber mechanics. First, we simulated cardiovascular mechanics of a healthy adult at rest. Size and mass of heart and blood vessels were adapted so that mechanical tissue load was normalized. Second, compensated PAH was simulated by increasing mean pulmonary artery pressure to 32 mmHg while applying load adaptation. Third, decompensated PAH was simulated by increasing mean pulmonary artery pressure further to 79 mmHg without further adaptation. Finally, early RVfw pacing was simulated in severely decompensated PAH. Time courses of circumferential strain in the ventricular walls as simulated were similar to the ones measured in healthy subjects (uniform strain patterns) and in PAH patients (prolonged RVfw shortening). When simulating pacing in decompensated PAH, RV pump function was best upon 40-ms RVfw preexcitation, as evidenced by maximal decrease of RV end-diastolic volume, reduced RVfw myofiber work, and most homogeneous distribution of workload over the ventricular walls. Thus our simulations indicate that, in decompensated PAH, RVfw pacing may improve RV pump function and may homogenize workload over the ventricular walls.

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