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Hypoxic pulmonary vasoconstriction

Hiroki Ota, Keishi Sugino, Toshimasa Uekusa, Tamiko Takemura, Sakae Homma
A 63-year-old man with sarcoidosis-associated pulmonary hypertension (SAPH) died suddenly of decompensated right heart failure. At autopsy, microscopy showed subpleural and interlobular fibrosis in both upper lobes, with marked broncho-bronchiolectasis, as well as bronchovascular bundle fibrosis and fibrotic organization in alveolar lumens, which are consistent with pulmonary sarcoidosis. Intimal fibrosis and medial hypertrophy were noted in the proximal elastic to distal muscular pulmonary arteries (Heath-Edwards, grades II-III) within intensive fibrotic lesions...
November 2016: Respiratory Investigation
Hae Jin Kim, Hae Young Yoo
Pulmonary arterial hypertension (PAH) is a progressive disease characterized by vascular remodeling of pulmonary arteries (PAs) and increased vascular resistance in the lung. Monocrotaline (MCT), a toxic alkaloid, is widely used for developing rat models of PAH caused by injury to pulmonary endothelial cells; however, characteristics of vascular functions in MCT-induced PAH vary and are not fully understood. Here, we investigated hypoxic pulmonary vasoconstriction (HPV) responses and effects of various vasoconstrictors with isolated/perfused lungs of MCT-induced PAH (PAH-MCT) rats...
November 2016: Korean Journal of Physiology & Pharmacology
Martin Wepler, Arkadi Beloiartsev, Mary D Buswell, Dipak Panigrahy, Rajeev Malhotra, Emmanuel S Buys, Peter Radermacher, Fumito Ichinose, Donald B Bloch, Warren M Zapol
RATIONALE: Hypoxic pulmonary vasoconstriction (HPV) is the response of the pulmonary vasculature to low levels of alveolar oxygen. HPV improves systemic arterial oxygenation by matching pulmonary perfusion to ventilation during alveolar hypoxia, and is impaired in lung diseases such as the acute respiratory distress syndrome (ARDS) and in experimental models of endotoxemia. Epoxyeicosatrienoic acids (EETs) are pulmonary vasoconstrictors, which are metabolized to less vasoactive dihydroxyeicosatrienoic acids (DHETs) by soluble epoxide hydrolase (sEH)...
November 4, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
Chaminda R Samarage, Richard Carnibella, Melissa Preissner, Heather D Jones, James T Pearson, Andreas Fouras, Stephen Dubsky
PURPOSE: In vivo imaging of the pulmonary vasculature in small animals is difficult yet highly desirable in order to allow study of the effects of a host of dynamic biological processes such as hypoxic pulmonary vasoconstriction. Here the authors present an approach for the quantification of changes in the vasculature. METHODS: A contrast free angiography technique is validated in silico through the use of computer-generated images and in vivo through microcomputed tomography (μCT) of live mice conducted using a laboratory-based x-ray source...
November 2016: Medical Physics
Paul M Heerdt, David F Stowe
PURPOSE OF REVIEW: To summarize what is currently known about the relationship between single-lung ventilation (SLV), oxidative stress, and postoperative disruption of organ function. RECENT FINDINGS: SLV produces progressive alelectasis that is associated with hypoxic pulmonary vasoconstriction and redistribution of blood flow away from the nonventilated lung. This local tissue hypoxia induces the generation of reactive oxygen and reactive nitrogen species, an effect subsequently amplified by lung re-expansion consistent with well described hypoxia/reperfusion responses...
October 25, 2016: Current Opinion in Anaesthesiology
Natasha M Rogers, Maryam Sharifi-Sanjani, Mingyi Yao, Kedar Ghimire, Raquel Bienes-Martinez, Stephanie M Mutchler, Heather E Knupp, Jeffrey Baust, Enrico M Novelli, Mark Ross, Claudette St Croix, Johannes C Kutten, Caitlin A Czajka, John C Sembrat, Mauricio Rojas, David Labrousse-Arias, Timothy N Bachman, Rebecca R Vanderpool, Brian S Zuckerbraun, Hunter C Champion, Ana L Mora, Adam C Straub, Richard A Bilonick, Maria J Calzada, Jeffrey S Isenberg
AIMS: Thrombospondin-1 (TSP1) is a ligand for CD47 and TSP1(-/-) mice are protected from pulmonary hypertension (PH). We hypothesized the TSP1-CD47 axis is upregulated in human PH and promotes pulmonary arterial vasculopathy. METHODS AND RESULTS: We analyzed the molecular signature and functional response of lung tissue and distal pulmonary arteries (PAs) from individuals with (n=23) and without (n=16) PH. Compared to controls, lungs and distal PAs from PH patients showed induction of TSP1-CD47 and endothelin-1/endothelin A receptor (ET-1/ETA) protein and mRNA...
October 13, 2016: Cardiovascular Research
Sachindra Raj Joshi, Anand Lakhkar, Vidhi Dhagia, Ariadne L Zias, Vasiliki Soldatos, Kaori Oshima, Houli Jiang, Katherine Gotlinger, Jorge H Capdevila, Michal L Schwartzman, Ivan F McMurtry, Sachin A Gupte
Epoxyeicosatrienoicacids (EETs), synthesized from arachidonic acid by epoxygenases of the CYP2C and CYP2J gene subfamilies, contribute to hypoxic pulmonary vasoconstriction (HPV) in mice. Despite their roles in HPV, it is controversial whether EETs mediate or ameliorate pulmonary hypertension (PH). A recent study showed that deficiency of Cyp2j did not protect male and female mice from hypoxia-induced PH. Since CYP2C44 is a functionally important epoxygenase, we hypothesized that knockout of the Cyp2c44 gene would protect both sexes of mice from hypoxia-induced PH...
September 2016: Pulmonary Circulation
Bodo Davieds, Julian Gross, Marc M Berger, Emel Baloğlu, Peter Bärtsch, Heimo Mairbäurl
Oxygen diffusion across the alveolar wall is compromised by low alveolar oxygen but also by pulmonary edema, and leads to hypoxemia and hypoxic pulmonary vasoconstriction (HPV). To test, whether inhibition of alveolar fluid reabsorption results in an increased pulmonary arterial pressure and whether this effect enhances HPV, we established a model, where anesthetized rats were ventilated with normoxic (21% O2) and hypoxic (13.5% O2) gas received aerosolized amiloride and lipopolisaccharide (LPS) to inhibit alveolar fluid reabsorption...
September 2016: Physiological Reports
Kimberly J Dunham-Snary, Danchen Wu, Edward A Sykes, Amar Thakrar, Leah Rg Parlow, Jeffrey D Mewburn, Joel L Parlow, Stephen L Archer
Hypoxic pulmonary vasoconstriction (HPV) is a homeostatic mechanism that is intrinsic to the pulmonary vasculature. Intrapulmonary arteries constrict in response to alveolar hypoxia, diverting blood to better-oxygenated lung segments, thereby optimizing ventilation-perfusion matching and systemic oxygen delivery. In response to alveolar hypoxia, a mitochondrial sensor dynamically changes reactive oxygen species and redox couples in PASMC. This inhibits potassium channels, depolarizes PASMC, activates voltage-gated calcium channels, and increases cytosolic calcium, causing vasoconstriction...
September 16, 2016: Chest
Andrzej Fedorowicz, Łukasz Mateuszuk, Grzegorz Kopec, Tomasz Skórka, Barbara Kutryb-Zając, Agnieszka Zakrzewska, Maria Walczak, Andrzej Jakubowski, Magdalena Łomnicka, Ewa Słomińska, Stefan Chlopicki
BACKGROUND: Pulmonary arterial hypertension (PAH) is associated with inflammatory response but it is unknown whether it is associated with alterations in NNMT activity and MNA plasma concentration. Here we examined changes in NNMT-MNA pathway in PAH in rats and humans. METHODS: PAH in rats was induced by a single subcutaneous injection of MCT (60 mg/kg). Changes in NNMT activity in the lungs and liver (assessed as the rate of conversion of nicotinamide (NA) to MNA), changes in plasma concentration of MNA and its metabolites (analyzed by LC/MS) were analyzed in relation to PAH progression...
2016: Respiratory Research
A Mark Evans, Amira D Mahmoud, Javier Moral-Sanz, Sandy Hartmann
Regulation of breathing is critical to our capacity to accommodate deficits in oxygen availability and demand during, for example, sleep and ascent to altitude. It is generally accepted that a fall in arterial oxygen increases afferent discharge from the carotid bodies to the brainstem and thus delivers increased ventilatory drive, which restores oxygen supply and protects against hypoventilation and apnoea. However, the precise molecular mechanisms involved remain unclear. We recently identified as critical to this process the AMP-activated protein kinase (AMPK), which is key to the cell-autonomous regulation of metabolic homoeostasis...
September 1, 2016: Biochemical Journal
Mengxiao Zheng, Meiping Zhao, Lanlan Tang, Congcong Zhang, Longsheng Song, Wantie Wang
BACKGROUND: Pulmonary arterial hypertension (PAH) is a fatal disease characterized by increased pulmonary arteriolar resistance. Pulmonary vasoconstriction has been proved to play a significant role in PAH. We previously reported that Panax notoginseng saponins (PNS) might attenuate hypoxia and hypercapnia-induced pulmonary vasoconstriction (HHPV). METHODS: In the present study, our specific objective was to investigate the role of ginsenoside Rg1, a major component of PNS, in this process and the possible underlying mechanism...
July 2016: Journal of Thoracic Disease
Christophe Guignabert, Carole Phan, Andrei Seferian, Alice Huertas, Ly Tu, Raphaël Thuillet, Caroline Sattler, Morane Le Hiress, Yuichi Tamura, Etienne-Marie Jutant, Marie-Camille Chaumais, Stéphane Bouchet, Benjamin Manéglier, Mathieu Molimard, Philippe Rousselot, Olivier Sitbon, Gérald Simonneau, David Montani, Marc Humbert
Pulmonary arterial hypertension (PAH) is a life-threatening disease that can be induced by dasatinib, a dual Src and BCR-ABL tyrosine kinase inhibitor that is used to treat chronic myelogenous leukemia (CML). Today, key questions remain regarding the mechanisms involved in the long-term development of dasatinib-induced PAH. Here, we demonstrated that chronic dasatinib therapy causes pulmonary endothelial damage in humans and rodents. We found that dasatinib treatment attenuated hypoxic pulmonary vasoconstriction responses and increased susceptibility to experimental pulmonary hypertension (PH) in rats, but these effects were absent in rats treated with imatinib, another BCR-ABL tyrosine kinase inhibitor...
September 1, 2016: Journal of Clinical Investigation
K Schmidt, R Windler, C de Wit
A swarm of fish displays a collective behavior (swarm behavior) and moves "en masse" despite the huge number of individual animals. In analogy, organ function is supported by a huge number of cells that act in an orchestrated fashion and this applies also to vascular cells along the vessel length. It is obvious that communication is required to achieve this vital goal. Gap junctions with their modular bricks, connexins (Cxs), provide channels that interlink the cytosol of adjacent cells by a pore sealed against the extracellular space...
2016: Advances in Pharmacology
Andrew S Cowburn, Alexi Crosby, David Macias, Cristina Branco, Renato D D R Colaço, Mark Southwood, Mark Toshner, Laura E Crotty Alexander, Nicholas W Morrell, Edwin R Chilvers, Randall S Johnson
Hypoxic pulmonary vasoconstriction is correlated with pulmonary vascular remodeling. The hypoxia-inducible transcription factors (HIFs) HIF-1α and HIF-2α are known to contribute to the process of hypoxic pulmonary vascular remodeling; however, the specific role of pulmonary endothelial HIF expression in this process, and in the physiological process of vasoconstriction in response to hypoxia, remains unclear. Here we show that pulmonary endothelial HIF-2α is a critical regulator of hypoxia-induced pulmonary arterial hypertension...
August 2, 2016: Proceedings of the National Academy of Sciences of the United States of America
Liping Zhu, Jiwei Zhang, Juan Zhou, Yankai Lu, Songling Huang, Rui Xiao, Xiangyuan Yu, Xianqin Zeng, Bingxun Liu, Fangbo Liu, Mengxiang Sun, Mao Dai, Qiang Hao, Jiansha Li, Tao Wang, Tongfei Li, Qinghua Hu
Mitochondria are essential for the onset of hypoxia-induced pulmonary vasoconstriction and pulmonary vascular-remodeling, two major aspects underlying the development of pulmonary hypertension, an incurable disease. However, hypoxia induces relaxation of systemic arteries such as femoral arteries and mitochondrial heterogeneity controls the distinct responses of pulmonary versus femoral artery smooth muscle cells to hypoxia in vitro. The aim of this study was to determine whether mitochondrial heterogeneity can be experimentally exploited in vivo for a potential treatment against pulmonary hypertension...
July 13, 2016: Oncotarget
A H Toro-Salinas, N Fort, J R Torrella, T Pagès, C Javierre, G Viscor
The increase in pulmonary arterial pressure (PAP) due to hypoxic pulmonary vasoconstriction (HPV) could be a limiting factor for physical performance during hypoxic exposure. Sildenafil has been shown to reduce PAP in situations of moderate or severe hypoxia, and consequently its role as an ergogenic aid and even a possible doping substance must be considered. We performed a double-blind crossover study to determine the effects of sildenafil on cardiovascular, respiratory and metabolic parameters in normoxia and during acute exposure to hypobaric hypoxia (4 000 m) at rest and during maximal and submaximal (60% VO2 max) exercise tests...
September 2016: International Journal of Sports Medicine
Remco R Berendsen, Rob C Lindeman, Merel Boom, Leon P H J Aarts, Eveline L A van Dorp, Luc J Teppema
Sustained and chronic hypoxia lead to a rise in pulmonary ventilation (hypoxic ventilatory response, HVR) and to an increase in pulmonary vascular resistance (hypoxic pulmonary vasoconstriction, HPV). In this study, we examined the effect of a clinical intravenous dose of recombinant human erythropoietin (rHuEPO,50 IU kg(-1) ) on the isocapnic HVR and HPV in 7 male and 7 female subjects by exposing them to hypoxia for 20 min (end-tidal PO2  ∼ 50 mmHg) while measuring their ventilation and estimating pulmonary arterial pressure from the maximal velocity of the regurgitant jet over the tricuspid valve during systole (ΔPmax) with echocardiography...
July 13, 2016: Experimental Physiology
Jon C Inkrott
Understanding the hypoxic drive and release of hypoxic vasoconstriction in the chronic obstructive pulmonary disease population can be somewhat confusing and misunderstood. Furthermore, the hypoxic drive theory is one in which there really is no scientific evidence to support and yet continues to prosper in every aspect of care in regard to the chronic lung patient, from prehospital all the way to intensive care unit and home care therapy. This subject review will hopefully enhance some understanding of what exactly goes on with these patients and the importance of providing oxygen when it is desperately needed...
July 2016: Air Medical Journal
D Kylhammar, G Rådegran
Hypoxic pulmonary vasoconstriction (HPV) serves to optimize ventilation-perfusion matching in focal hypoxia and thereby enhances pulmonary gas exchange. During global hypoxia, however, HPV induces general pulmonary vasoconstriction, which may lead to pulmonary hypertension (PH), impaired exercise capacity, right-heart failure and pulmonary oedema at high altitude. In chronic hypoxia, generalized HPV together with hypoxic pulmonary arterial remodelling, contribute to the development of PH. The present article reviews the principal pathways in the in vivo modulation of HPV, hypoxic pulmonary arterial remodelling and PH with primary focus on the endothelin-1, nitric oxide, cyclooxygenase and adenine nucleotide pathways...
July 6, 2016: Acta Physiologica
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