In vivo calibration of electromagnetic flowmeter probes on pulmonary artery and aorta

1968 ◽  
Vol 25 (4) ◽  
pp. 455-460 ◽  
Author(s):  
Kenneth C. Weber ◽  
James C. Engle ◽  
Gary W. Lyons ◽  
Arthur J. Madsen ◽  
Irwin J. Fox
Keyword(s):  
Pulmonary Artery ◽  
Electromagnetic Flowmeter ◽  
In Vivo Calibration

Endogenous hydrogen sulfide sulfhydrates IKKβ at cysteine 179 to control pulmonary artery endothelial cell inflammation

2019 ◽  
Vol 133 (20) ◽  
pp. 2045-2059 ◽  
Author(s):  
Da Zhang ◽  
Xiuli Wang ◽  
Siyao Chen ◽  
Selena Chen ◽  
Wen Yu ◽  
...  
Keyword(s):  
Hydrogen Sulfide ◽  
Endothelial Cell ◽  
Pulmonary Artery ◽  
Cell Model ◽  
Site Directed Mutagenesis ◽  
Critical Event ◽  
Hypertensive Rats ◽  
Pulmonary Artery Endothelial Cell

Abstract Background: Pulmonary artery endothelial cell (PAEC) inflammation is a critical event in the development of pulmonary arterial hypertension (PAH). However, the pathogenesis of PAEC inflammation remains unclear. Methods: Purified recombinant human inhibitor of κB kinase subunit β (IKKβ) protein, human PAECs and monocrotaline-induced pulmonary hypertensive rats were employed in the study. Site-directed mutagenesis, gene knockdown or overexpression were conducted to manipulate the expression or activity of a target protein. Results: We showed that hydrogen sulfide (H2S) inhibited IKKβ activation in the cell model of human PAEC inflammation induced by monocrotaline pyrrole-stimulation or knockdown of cystathionine γ-lyase (CSE), an H2S generating enzyme. Mechanistically, H2S was proved to inhibit IKKβ activity directly via sulfhydrating IKKβ at cysteinyl residue 179 (C179) in purified recombinant IKKβ protein in vitro, whereas thiol reductant dithiothreitol (DTT) reversed H2S-induced IKKβ inactivation. Furthermore, to demonstrate the significance of IKKβ sulfhydration by H2S in the development of PAEC inflammation, we mutated C179 to serine (C179S) in IKKβ. In purified IKKβ protein, C179S mutation of IKKβ abolished H2S-induced IKKβ sulfhydration and the subsequent IKKβ inactivation. In human PAECs, C179S mutation of IKKβ blocked H2S-inhibited IKKβ activation and PAEC inflammatory response. In pulmonary hypertensive rats, C179S mutation of IKKβ abolished the inhibitory effect of H2S on IKKβ activation and pulmonary vascular inflammation and remodeling. Conclusion: Collectively, our in vivo and in vitro findings demonstrated, for the first time, that endogenous H2S directly inactivated IKKβ via sulfhydrating IKKβ at Cys179 to inhibit nuclear factor-κB (NF-κB) pathway activation and thereby control PAEC inflammation in PAH.

scholarly journals In vivo calibration of the T2* cardiovascular magnetic resonance method at 1.5 T for estimation of cardiac iron in a minipig model of transfusional iron overload

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Peter Diedrich Jensen ◽  
Asbjørn Haaning Nielsen ◽  
Carsten Wiberg Simonsen ◽  
Ulrik Thorngren Baandrup ◽  
Svend Eggert Jensen ◽  
...  
Keyword(s):  
Rank Correlation ◽  
Calibration Data ◽  
Iron Loading ◽  
Spearman Rank Correlation ◽  
Calibration Equation ◽  
Spearman Rank ◽  
Cardiac Iron ◽  
In Vivo Calibration ◽  
Spearman Rank Correlation Coefficient

Abstract Background Non-invasive estimation of the cardiac iron concentration (CIC) by T2* cardiovascular magnetic resonance (CMR) has been validated repeatedly and is in widespread clinical use. However, calibration data are limited, and mostly from post-mortem studies. In the present study, we performed an in vivo calibration in a dextran-iron loaded minipig model. Methods R2* (= 1/T2*) was assessed in vivo by 1.5 T CMR in the cardiac septum. Chemical CIC was assessed by inductively coupled plasma-optical emission spectroscopy in endomyocardial catheter biopsies (EMBs) from cardiac septum taken during follow up of 11 minipigs on dextran-iron loading, and also in full-wall biopsies from cardiac septum, taken post-mortem in another 16  minipigs, after completed iron loading. Results A strong correlation could be demonstrated between chemical CIC in 55 EMBs and parallel cardiac T2* (Spearman rank correlation coefficient 0.72, P < 0.001). Regression analysis led to [CIC] = (R2* − 17.16)/41.12 for the calibration equation with CIC in mg/g dry weight and R2* in Hz. An even stronger correlation was found, when chemical CIC was measured by full-wall biopsies from cardiac septum, taken immediately after euthanasia, in connection with the last CMR session after finished iron loading (Spearman rank correlation coefficient 0.95 (P < 0.001). Regression analysis led to the calibration equation [CIC] = (R2* − 17.2)/31.8. Conclusions Calibration of cardiac T2* by EMBs is possible in the minipig model but is less accurate than by full-wall biopsies. Likely explanations are sampling error, variable content of non-iron containing tissue and smaller biopsies, when using catheter biopsies. The results further validate the CMR T2* technique for estimation of cardiac iron in conditions with iron overload and add to the limited calibration data published earlier.

Stem Cell–Derived, Tissue-Engineered Pulmonary Artery Augmentation Patches In Vivo

2008 ◽  
Vol 86 (1) ◽  
pp. 132-141 ◽  
Author(s):  
Bret A. Mettler ◽  
Virna L. Sales ◽  
Chaz L. Stucken ◽  
Vesa Anttila ◽  
Karen Mendelson ◽  
...  
Keyword(s):  
Stem Cell ◽  
Pulmonary Artery

THE ADJUSTABLE SYSTEMIC-PULMONARY ARTERY SHUNT OFFERS PRECISE CONTROL OF FLOW IN VIVO

ASAIO Journal ◽  
2006 ◽  
Vol 52 (2) ◽  
pp. 21A
Author(s):  
William I Douglas ◽  
Karabeth B Moore ◽  
Phillip R Resig ◽  
Charles F Knapp ◽  
Jamey D Jacob
Keyword(s):  
Pulmonary Artery ◽  
Precise Control ◽  
Control Of Flow

scholarly journals Galectin-3- Mediated Transdifferentiation of Pulmonary Artery Endothelial Cells Contributes to Hypoxic Pulmonary Vascular Remodeling

2018 ◽  
Vol 51 (2) ◽  
pp. 763-777 ◽  
Author(s):  
Li Zhang ◽  
Yu-mei Li ◽  
Xi-xi Zeng ◽  
Xiao-yan Wang ◽  
Shao-kun Chen ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Endothelial Cells ◽  
Endothelial Cell ◽  
Pulmonary Artery ◽  
Ultrasound Biomicroscopy ◽  
Pulmonary Artery Hypertension ◽  
Carbohydrate Binding ◽  
Vessel Remodeling ◽  
Galectin 3

Background/Aims: Vascular muscularity is a key event in vessel remodeling during pulmonary artery hypertension (PAH). Endothelial-mesenchymal transdifferentiation (EndMT) has been increasingly reported to play a role in disease occurrence. Galectin-3, a carbohydrate-binding protein regulates cell proliferation, differentiation, migration and neovascularization. However, whether galectin-3 controls endothelial cell transdifferentiation during the development of PAH is unknown. Methods: Rats were exposed to normoxic or hypoxic conditions (fraction of inspired O2 0.10) for 21 d to establish PAH models. Hemodynamic changes were evaluated through surgery of the right jugular vein and ultrasound biomicroscopy inviVue. And vessel pathological alterations were detected by H&E staining. Galectin-3 (Gal-3)-induced pulmonary artery endothelium cell (PAEC) dynamic alterations were measured by MTT assays, Cell immunofluorescence, Flow cytometry, Real-time PCR and Western blot. Results: Our study demonstrated that Gal-3 was expressed in hypoxic pulmonary vascular adventitia and intima. The increased Gal-3 expression was responsible for hypoxic vessel remodeling and PAH development in vivo. Gal-3 was found to inhibit cell proliferation and apoptosis in cultured endothelial cells. Meanwhile endothelial cell morphology was altered and exhibited smooth muscle-like cell features as demonstrated by the expression of α-SMA after Gal-3 treatment. Gal-3 activated Jagged1/Notch1 pathways and induced MyoD and SRF. When MyoD or SRF were silenced with siRNAs, Gal-3-initiated transdifferentiation in endothelial cells was blocked as indicated by a lack of α-SMA. Conclusion: These results suggest that Gal-3 induces PAECs to acquire an α-SMA phenotype via a transdifferentiation process which depends on the activation of Jagged1/Notch1 pathways that mediate MyoD and SRF expression.

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.

Egr-1 antisense oligonucleotides inhibit hypoxia-induced proliferation of pulmonary artery adventitial fibroblasts

2005 ◽  
Vol 98 (2) ◽  
pp. 732-738 ◽  
Author(s):  
Mark F. Banks ◽  
Evgenia V. Gerasimovskaya ◽  
Doug A. Tucker ◽  
Maria G. Frid ◽  
Todd C. Carpenter ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Pulmonary Artery ◽  
Antisense Oligonucleotides ◽  
Mammalian Species ◽  
Growth Factor Receptor ◽  
Immunohistochemical Analysis ◽  
Fibroblast Proliferation ◽  
Adventitial Fibroblasts ◽  
Adventitial Fibroblast

In most mammalian species, chronic exposure to hypoxia leads to pulmonary hypertension and vascular remodeling. The adventitial fibroblast, because of its ability to proliferate in response to hypoxia, is thought to be a critical cell in the remodeling process. However, the transcription factors driving hypoxia-induced fibroblast proliferation have yet to be elucidated. The early growth response-1 (Egr-1) transcription factor has been shown to be upregulated by hypoxia in pulmonary artery adventitial fibroblasts. We therefore hypothesized that Egr-1 is directly involved in hypoxia-induced adventitial fibroblast proliferation. Immunohistochemical analysis of in vivo lung tissue from animals exposed to chronic hypoxia revealed increased expression of Egr-1 in the pulmonary artery fibroblasts vs. expression shown in normoxic controls. In fibroblasts cultured from chronically hypoxic animals, exposure to 1% oxygen upregulated Egr-1 protein and cell proliferation. To evaluate the role of Egr-1 in hypoxia-induced proliferation, we employed an Egr-1 antisense strategy. Addition of antisense Egr-1 oligonucleotides, but not sense oligonucleotides, attenuated the hypoxia-induced upregulation of Egr-1 protein and reduced hypoxia-induced DNA synthesis by 50%. Cell proliferation was also significantly inhibited by the addition of antisense Egr-1 oligonucleotides but not the sense oligonucleotides. In addition, hypoxia-induced upregulations of cyclin D and epidermal growth factor receptor were attenuated by Egr-1 antisense oligonucleotides. We conclude that Egr-1 protein expression is very sensitive to upregulation by hypoxia in pulmonary artery adventitial fibroblasts and that it plays an important role in the autonomous growth phenotype induced by hypoxia in these cells.

scholarly journals SOD2 ameliorates pulmonary hypertension in a murine model of sleep apnea via suppressing expression of NLRP3 in CD11b+ cells

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Cuiping Fu ◽  
Shengyu Hao ◽  
Zilong Liu ◽  
Liang Xie ◽  
Xu Wu ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Sleep Apnea ◽  
Pulmonary Artery ◽  
Myeloid Cell ◽  
Apoptosis Resistance ◽  
Hypoxic Conditions ◽  
Pyrin Domain ◽  
Obstructive Sleep ◽  
Myeloid Cell Line

Abstract Background High prevalence of obstructive sleep apnea (OSA) in the pulmonary hypertension (PH) population suggests that chronic intermittent hypoxia (CIH) is an important pathogenic factor of PH. However, the exact mechanism of CIH induced PH is not clear. One of the molecules that plays a key role in regulating pulmonary artery function under hypoxic conditions is superoxide dismutase 2 (SOD2). Methods Our study utilized heterozygous SOD2−/+ mice firstly in CIH model to explore the exact role of SOD2 in CIH causing PH. Expression of SOD2 was analyzed in CIH model. Echocardiography and pulmonary hypertension were measured in wild type (WT) and SOD2−/+ mice under normal air or CIH condition. Hematoxylin–Eosin (H&E) staining and masson staining were carried out to evaluate pulmonary vascular muscularization and remodeling. Micro-PET scanning of in vivo 99mTc-labelled- MAG3-anti-CD11b was applied to assess CD11b in quantification and localization. Level of nod-like receptor pyrin domain containing 3 (NLRP3) was analyzed by real time PCR and immunohistochemistry (IHC). Results Results showed that SOD2 was down-regulated in OSA/CIH model. Deficiency of SOD2 aggravated CIH induced pulmonary hypertension and pulmonary vascular hypertrophy. CD11b+ cells, especially monocytic myeloid cell line-Ly6C+Ly6G− cells, were increased in the lung, bone marrow and the blood under CIH condition, and down-regulated SOD2 activated NLRP3 in CD11b+ cells. SOD2-deficient-CD11b+ myeloid cells promoted the apoptosis resistance and over-proliferation of human pulmonary artery smooth muscle cells (PASMCs) via up-regulating NLRP3. Conclusion CIH induced down-regulating of SOD2 increased pulmonary hypertension and vascular muscularization. It could be one of the mechanism of CIH leading to PH.

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