Hypoxia (Auckland, N.Z.)最新文献

{"title":"Reperfusion Microvascular Ischemia After Prolonged Coronary Occlusion: Implications And Treatment With Local Supersaturated Oxygen Delivery","authors":"J. Spears","doi":"10.2147/HP.S217955","DOIUrl":"https://doi.org/10.2147/HP.S217955","url":null,"abstract":"Abstract Following a prolonged coronary arterial occlusion, heterogeneously scattered, focal regions of low erythrocyte flow are commonly found throughout the reperfused myocardium. Experimental studies have also demonstrated the presence of widespread, focally patchy regions of microvascular ischemia during reperfusion (RMI). However, the potential contribution of RMI to tissue viability and function has received little attention in the absence of practical clinical methods for its detection. In this review, the anatomic/functional basis of RMI is summarized, along with the evidence for its presence in reperfused myocardium. Advances in microcirculation research related to obstructive responses of vascular endothelial cells and blood elements to the effects of hypoxia and low shear stress are discussed, and a potential cycle of intensification of RMI from such responses and progressive loss of functional capillary density is presented. In capillaries with impaired erythrocyte flow, compensatory increases in the delivery of oxygen, because of its low solubility in plasma, are effective only at high partial pressures. As discussed herein, attenuation of the cycle with oxygen at hyperbaric levels in plasma is, very likely, responsible for improved tissue level perfusion noted experimentally. Observed clinical benefits from intracoronary SuperSaturated oxygen (SSO2) delivery, including infarct size reduction, can be attributed to attenuation of RMI with improvement in microvascular blood flow.","PeriodicalId":73270,"journal":{"name":"Hypoxia (Auckland, N.Z.)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/HP.S217955","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42351220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hypoxia Suppresses High Fat Diet-Induced Steatosis And Development Of Hepatic Adenomas","authors":"Nathan W. Sweeney, Cecil J. Gomes, R. De Armond, Sara M Centuori, S. Parthasarathy, Jesse D. Martinez","doi":"10.2147/HP.S217569","DOIUrl":"https://doi.org/10.2147/HP.S217569","url":null,"abstract":"Purpose Nonalcoholic fatty liver disease (NAFLD) is considered the most common form of silent liver disease in the United States and obesity is associated with increased risk of NAFLD. Obstructive sleep apnea (OSA) which is common in obese individuals is associated with a greater incidence of NAFLD, which in turn, increases the risk for hepatocellular carcinoma (HCC). It is unclear how obesity, OSA and NAFLD interrelate nor how they collectively contribute to an increased risk for developing HCC. Patients and methods Male BALB/c mice were exposed to diethylnitrosamine and phenobarbital followed by 48 weeks of either standard chow diet (chow), chow with hypoxia, high-fat diet, or a combination of hypoxia and high-fat diet. We noninvasively monitored tumor development using micro-CT imaging. We tracked the total weight gained throughout the study. We evaluated liver histology, fat accumulation, carbonic anhydrase 9 (CA9) and hypoxia-inducible factor 1-alpha (HIF-1α) expression, as well as, serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Results A high-fat diet without hypoxia led to the development of obesity that induced hepatic steatosis and promoted tumorigenesis. Animals on a high-fat diet and that were also exposed to hypoxia had lower total weight gain, lower steatosis, lower serum AST and ALT levels, and fewer number of hepatic adenomas than a high-fat diet without hypoxia. Conclusion These findings suggest that hypoxia abrogates obesity, hepatic steatosis, and hepatic tumorigenesis related to a high-fat diet.","PeriodicalId":73270,"journal":{"name":"Hypoxia (Auckland, N.Z.)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/HP.S217569","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44435045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Separate and combined effects of hypobaric hypoxia and hindlimb suspension on skeletal homeostasis and hematopoiesis in mice","authors":"Marjorie Durand, J. Collombet, S. Frasca, Véronique Sarilar, J. Lataillade, M. Le Bousse-Kerdilès, X. Holy","doi":"10.2147/HP.S195827","DOIUrl":"https://doi.org/10.2147/HP.S195827","url":null,"abstract":"Purpose Bone marrow response to an organismal stress is made by orchestrating the interplay between hematopoietic stem/progenitor cells (HSPCs) and mesenchymal stromal cells (MSCs). Neither the cellular nor the molecular factors that regulate this process are fully understood, especially since this mechanism probably varies depending on the type of stress. Herein, we explored the differentiation and fate of MSCs and HSPCs in mice challenged with a hematopoietic stress or a mechanical stress applied separately or in combination. Methods Mice were subjected to 4 days of hypobaric hypoxia (hematopoietic challenge) and/or 7 days of hindlimb suspension (stromal challenge) and then sacrificed for blood and bone collection. Using hematological measurements, colony-forming unit assays, bone histomorphometry and array-based multiplex ELISA analysis, we evaluated challenge influences on both MSC and HSPC mobilization, differentiation (osteoblasts, osteoclasts, and mature blood cells) and fate. Results We found that hypoxia leads to HSPC mobilization and that an imbalance between bone formation and bone resorption accounts for this mobilization. Whilst suspension is also associated with an imbalance between bone formation and bone resorption, it does not induce HSPC mobilization. Then, we revealed cellular interactions by combining hematopoietic and stromal challenges together in mice. We showed that the hypoxia-driven HSPC mobilization is moderated by suspension. Moreover, when applied in a hypoxic environment, suspension offsets bone imbalance. We identified stroma cell-derived factors MIP-1α, HGF and SDF-1 as potent molecular key players sustaining interactions between hindlimb suspension and hypobaric hypoxia. Conclusion Taken together, our data highlight the benefit of combining different types of stress to better understand the interplay between MSCs and HSPCs.","PeriodicalId":73270,"journal":{"name":"Hypoxia (Auckland, N.Z.)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/HP.S195827","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42328976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of pseudohypoxia in the pathogenesis of type 2 diabetes.","authors":"Jing Song,&nbsp;Xiaojuan Yang,&nbsp;Liang-Jun Yan","doi":"10.2147/HP.S202775","DOIUrl":"https://doi.org/10.2147/HP.S202775","url":null,"abstract":"<p><p>Type 2 diabetes is caused by persistent high blood glucose, which is known as diabetic hyperglycemia. This hyperglycemic situation, when not controlled, can overproduce NADH and lower nicotinamide adenine dinucleotide (NAD), thereby creating NADH/NAD redox imbalance and leading to cellular pseudohypoxia. In this review, we discussed two major enzymatic systems that are activated by diabetic hyperglycemia and are involved in creation of this pseudohypoxic condition. One system is aldose reductase in the polyol pathway, and the other is poly (ADP ribose) polymerase. While aldose reductase drives overproduction of NADH, PARP could in contrast deplete NAD. Therefore, activation of the two pathways underlies the major mechanisms of NADH/NAD redox imbalance and diabetic pseudohypoxia. Consequently, reductive stress occurs, followed by oxidative stress and eventual cell death and tissue dysfunction. Additionally, fructose formed in the polyol pathway can also cause metabolic syndrome such as hypertension and nonalcoholic fatty liver disease. Moreover, pseudohypoxia can also lower sirtuin protein contents and induce protein acetylation which can impair protein function. Finally, we discussed the possibility of using nicotinamide riboside, an NAD precursor, as a promising therapeutic agent for restoring NADH/NAD redox balance and for preventing the occurrence of diabetic pseudohypoxia.</p>","PeriodicalId":73270,"journal":{"name":"Hypoxia (Auckland, N.Z.)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/HP.S202775","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37362003","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ascorbate modulates the hypoxic pathway by increasing intracellular activity of the HIF hydroxylases in renal cell carcinoma cells.","authors":"Christina Wohlrab,&nbsp;Caroline Kuiper,&nbsp;Margreet Cm Vissers,&nbsp;Elisabeth Phillips,&nbsp;Bridget A Robinson,&nbsp;Gabi U Dachs","doi":"10.2147/HP.S201643","DOIUrl":"https://doi.org/10.2147/HP.S201643","url":null,"abstract":"<p><p><b>Purpose:</b> Protein levels and activity of the hypoxia-inducible transcription factors HIF-1 and HIF-2 are controlled by hydroxylation of the regulatory alpha chains. Proline hydroxylases (PHDs) target the protein for degradation via the von-Hippel-Lindau (VHL)-ubiquitin-ligase complex, and asparagine hydroxylation by Factor Inhibiting HIF (FIH) leads to transcriptional inactivation. In cell-free systems, these enzymes require ascorbate as a cofactor, and this is also inferred to be an intracellular requirement for effective hydroxylation. However, how intracellular concentrations of ascorbate affect hydroxylase activity is unknown. In this study, we investigated the modulation of the regulatory hydroxylases in cancer cells by intracellular ascorbate. <b>Materials and methods:</b> To facilitate this investigation, we used clear cell renal carcinoma cell lines that were VHL-proficient (Caki-1), with a normal hypoxic response, or VHL-defective (Caki-2 and 786-0), with uncontrolled accumulation of HIF-α chains. We monitored the effect of intracellular ascorbate on the hypoxia-induced accumulation of HIF-1α, HIF-2α and the expression of downstream HIF targets BNIP3, cyclin D1 and GLUT1. Changes in hydroxylation of the HIF-1α protein in response to ascorbate were also investigated in 786-0 cells gene-modified to express full-length HIF-1α (786-HIF1). <b>Results:</b> In VHL-proficient cells, hypoxia induced accumulation of HIF-1α and BNIP3 which was dampened in mild hypoxia by elevated intracellular ascorbate. Increased HIF-2α accumulation occurred only under severe hypoxia and this was not modified by ascorbate availability. In VHL-defective cells, ascorbate supplementation induced additional accumulation of HIF under hypoxic conditions and HIF pathway proteins were unchanged by oxygen supply. In 786-HIF1 cells, levels of hydroxylated HIF-1α were elevated in response to increasing intracellular ascorbate levels. <b>Conclusion:</b> Our data provide evidence that the hypoxic pathway can be modulated by increasing HIF hydroxylase activity via intracellular ascorbate availability. In VHL-defective cells, accumulation of HIF-alpha proteins is independent of hydroxylation and is unaffected by intracellular ascorbate levels.</p>","PeriodicalId":73270,"journal":{"name":"Hypoxia (Auckland, N.Z.)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/HP.S201643","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37323117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aryl hydrocarbon receptor acts as a tumor suppressor in a syngeneic MC38 colon carcinoma tumor model.","authors":"Poonam Yakkundi,&nbsp;Eleanor Gonsalves,&nbsp;Maria Galou-Lameyer,&nbsp;Mark J Selby,&nbsp;William K Chan","doi":"10.2147/HP.S196301","DOIUrl":"https://doi.org/10.2147/HP.S196301","url":null,"abstract":"<p><p><b>Background:</b> Aryl hydrocarbon receptor (AHR), commonly known as an environmental sensor involved in the metabolism and elimination of xenobiotic substances, is also an important modulator in the development and functioning of the immune system. AHR expression is varied in the T cell subsets with the highest expression in T-helper 17 and T regulatory cells. It has been reported that AHR can act as a tumor promoter or a tumor suppressor, depending on the tumor type. <b>Methods:</b> In an effort to understand the role played by AHR in tumor growth, the MC38 syngeneic colon carcinoma tumor model was used on C57BL/6 or <i>ahr</i> knockout (KO, -/-) mice with or without AHR antagonist (CH223191) treatment. Tumor sizes were measured, and biomarkers were quantified in tumor microenvironment and draining lymph nodes using flow cytometry. Enzyme-linked immunosorbent assay was used to determine the amount of cytokines in tumors. <b>Results:</b> In <i>ahr</i> deficient mice, MC38 tumors progress more rapidly than in wild-type mice, accompanied by an increase in tumor-associated macrophages and M2 macrophages and a decrease in CD8a positive cytotoxic lymphocytes. Analysis of cytokines in the tumor microenvironment reveals a pro-inflammatory phenotype. Similar changes were observed by pharmacologic blockade of the receptor using CH223191. <b>Conclusion:</b> AHR acts as a tumor suppressor in mice implanted with MC38 colon carcinoma cells as evidenced by either a blockade or deficiency of AHR.</p>","PeriodicalId":73270,"journal":{"name":"Hypoxia (Auckland, N.Z.)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/HP.S196301","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37266951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Born to sense: biophysical analyses of the oxygen sensing prolyl hydroxylase from the simplest animal <i>Trichoplax adhaerens</i>.","authors":"Kerstin Lippl,&nbsp;Anna Boleininger,&nbsp;Michael A McDonough,&nbsp;Martine I Abboud,&nbsp;Hanna Tarhonskaya,&nbsp;Rasheduzzaman Chowdhury,&nbsp;Christoph Loenarz,&nbsp;Christopher J Schofield","doi":"10.2147/HP.S174655","DOIUrl":"https://doi.org/10.2147/HP.S174655","url":null,"abstract":"<p><strong>Background: </strong>In humans and other animals, the chronic hypoxic response is mediated by hypoxia inducible transcription factors (HIFs) which regulate the expression of genes that counteract the effects of limiting oxygen. Prolyl hydroxylases (PHDs) act as hypoxia sensors for the HIF system in organisms ranging from humans to the simplest animal <i>Trichoplax adhaerens</i>.</p><p><strong>Methods: </strong>We report structural and biochemical studies on the <i>T. adhaerens</i> HIF prolyl hydroxylase (<i>Ta</i>PHD) that inform about the evolution of hypoxia sensing in animals.</p><p><strong>Results: </strong>High resolution crystal structures (≤1.3 Å) of <i>Ta</i>PHD, with and without its HIFα substrate, reveal remarkable conservation of key active site elements between <i>T. adhaerens</i> and human PHDs, which also manifest in kinetic comparisons.</p><p><strong>Conclusion: </strong>Conserved structural features of <i>Ta</i>PHD and human PHDs include those apparently enabling the slow binding/reaction of oxygen with the active site Fe(II), the formation of a stable 2-oxoglutarate complex, and a stereoelectronically promoted change in conformation of the hydroxylated proline-residue. Comparison of substrate selectivity between the human PHDs and <i>Ta</i>PHD provides insights into the selectivity determinants of HIF binding by the PHDs, and into the evolution of the multiple HIFs and PHDs present in higher animals.</p>","PeriodicalId":73270,"journal":{"name":"Hypoxia (Auckland, N.Z.)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/HP.S174655","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36800761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Astrocyte HIF-2α supports learning in a passive avoidance paradigm under hypoxic stress.","authors":"Cindy V Leiton, Elyssa Chen, Alissa Cutrone, Kristy Conn, Kennelia Mellanson, Dania M Malik, Michael Klingener, Ryan Lamm, Michael Cutrone, John Petrie, Joher Sheikh, Adriana DiBua, Betsy Cohen, Thomas F Floyd","doi":"10.2147/HP.S173589","DOIUrl":"10.2147/HP.S173589","url":null,"abstract":"<p><strong>Background: </strong>The brain is extensively vascularized, useŝ20% of the body's oxygen, and is highly sensitive to changes in oxygen. While synaptic plasticity and memory are impaired in healthy individuals by exposure to mild hypoxia, aged individuals appear to be even more sensitive. Aging is associated with progressive failure in pulmonary and cardiovascular systems, exposing the aged to both chronic and superimposed acute hypoxia. The HIF proteins, the \"master regulators\" of the cellular response to hypoxia, are robustly expressed in neurons and astrocytes. Astrocytes support neurons and synaptic plasticity via complex metabolic and trophic mechanisms. The activity of HIF proteins in the brain is diminished with aging, and the increased exposure to chronic and acute hypoxia with aging combined with diminished HIF activity may impair synaptic plasticity.</p><p><strong>Purpose: </strong>Herein, we test the hypothesis that astrocyte HIF supports synaptic plasticity and learning upon hypoxia.</p><p><strong>Materials and methods: </strong>An Astrocyte-specific HIF loss-of-function model was employed, where knock-out of HIF-1α or HIF-2α in GFAP expressing cells was accomplished by cre-mediated recombination. Animals were tested for behavioral (open field and rotarod), learning (passive avoidance paradigm), and electrophysiological (long term potentiation) responses to mild hypoxic challenge.</p><p><strong>Results: </strong>In an astrocyte-specific HIF loss-of-function model followed by mild hypoxia, we identified that the depletion of HIF-2α resulted in an impaired passive avoidance learning performance. This was accompanied by an attenuated response to induction in long-term potentiation (LTP), suggesting that the hippocampal circuitry was perturbed upon hypoxic exposure following HIF-2α loss in astrocytes, and not due to hippocampal cell death. We investigated HIF-regulated trophic and metabolic target genes and found that they were not regulated by HIF-2α, suggesting that these specific targets may not be involved in mediating the phenotypes observed.</p><p><strong>Conclusion: </strong>Together, these results point to a role for HIF-2α in the astrocyte's regulatory role in synaptic plasticity and learning under hypoxia and suggest that even mild, acute hypoxic challenges can impair cognitive performance in the aged population who harbor impaired HIF function.</p>","PeriodicalId":73270,"journal":{"name":"Hypoxia (Auckland, N.Z.)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ba/35/hp-6-035.PMC6234990.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36800759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel approach to target hypoxic cancer cells via combining β-oxidation inhibitor etomoxir with radiation.","authors":"Arpit Dheeraj,&nbsp;Chapla Agarwal,&nbsp;Isabel R Schlaepfer,&nbsp;David Raben,&nbsp;Rana Singh,&nbsp;Rajesh Agarwal,&nbsp;Gagan Deep","doi":"10.2147/HP.S163115","DOIUrl":"https://doi.org/10.2147/HP.S163115","url":null,"abstract":"<p><strong>Background: </strong>Hypoxia in tumors is associated with resistance towards various therapies including radiotherapy. In this study, we assessed if hypoxia in cancer spheres could be effectively reduced by adding etomoxir (a β-oxidation inhibitor) immediately after cell irradiation.</p><p><strong>Methods: </strong>We employed cancer cells' sphere model to target hypoxia. Confocal imaging was used to analyze hypoxia and expression of specific biomarkers in spheres following various treatments (radiation and/or etomoxir).</p><p><strong>Results: </strong>Etomoxir (32.5 μM) treatment improved the radiation (2.5 Gy) efficacy against growth of lung adenocarcinoma H460 spheres. More importantly, radiation and etomoxir combination significantly reduced the hypoxic regions (pimonidazole+ areas) in H460 spheres compared to either treatment alone. Also, etomoxir and radiation combination treatment reduced the protein level of biomarkers for proliferation (Ki-67 and cyclin D1), stemness (CD44) and β-oxidation (CPT1A) in H460 spheres. We observed similar efficacy of etomoxir against growth of prostate cancer LNCaP cells' spheres when combined with radiation. Further, radiation treatment strongly reduced the hypoxic regions (pimonidazole+ areas) in CPT1 knockdown LNCaP cells' spheres.</p><p><strong>Conclusions: </strong>Together, these results offer a unique approach to target hypoxia in solid tumors via combining etomoxir with radiation, thereby improving therapeutic efficacy.</p>","PeriodicalId":73270,"journal":{"name":"Hypoxia (Auckland, N.Z.)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/HP.S163115","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36456209","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of human relaxin-2 (serelaxin) on hypoxic pulmonary vasoconstriction during acute hypoxia in a sheep model.","authors":"René Schiffner,&nbsp;Marius Nistor,&nbsp;Sabine Juliane Bischoff,&nbsp;Georg Matziolis,&nbsp;Martin Schmidt,&nbsp;Thomas Lehmann","doi":"10.2147/HP.S165092","DOIUrl":"https://doi.org/10.2147/HP.S165092","url":null,"abstract":"<p><strong>Purpose: </strong>Hypoxia induces pulmonary vasoconstriction with a subsequent increase of pulmonary artery pressure (PAP), which can result in pulmonary hypertension. Serelaxin has shown an increase of pulmonary hemodynamic parameters after serelaxin injection. We therefore investigated the response of pulmonary hemodynamic parameters after serelaxin administration in a clinically relevant model.</p><p><strong>Methods: </strong>Six controls and six sheep that received 30 μg/kg serelaxin underwent right heart catheterization during a 12-minute hypoxia period (inhalation of 5% oxygen and 95% nitrogen) and subsequent reoxygenation. Systolic, diastolic, and mean values of both PAP (respectively, PAPs, PAPd, and PAPm) and pulmonary capillary wedge pressure (respectively, PCWPs, PCWPd, and PCWPm), blood gases, heart rate (HR), and both peripheral and pulmonary arterial oxygen saturation were obtained. Cardiac output (CO), stroke volume (SV), pulmonary vascular resistance (PVR), pulmonary arterial compliance (PAcompl), and systemic vascular resistance (SVR) were calculated.</p><p><strong>Results: </strong>The key findings of the current study are that serelaxin prevents the rise of PAPs (<i>p</i>≤0.001), PAPm, PCWPm, PCWPs (<i>p</i>≤0.03), and PAPd (<i>p</i>≤0.05) during hypoxia, while it simultaneously increases CO and SV (<i>p</i>≤0.001). Similar courses of decreases of PAPm, PAPd, PAPs, CO, SVR (<i>p</i>≤0.001), and PCWPd (<i>p</i>≤0.03) as compared to hypoxic values were observed during reoxygenation. In direct comparison, the experimental groups differed during hypoxia in regard to HR, PAPm, PVR, and SVR (<i>p</i>≤0.03), and during reoxygenation in regard to HR (<i>p</i>≤0.001), PAPm, PAPs, PAPd, PVR, SVR (<i>p</i>≤0.03), and PCWPd (<i>p</i>≤0.05).</p><p><strong>Conclusion: </strong>The findings of this study suggest that serelaxin treatment improves pulmonary hemodynamic parameters during acute hypoxia.</p>","PeriodicalId":73270,"journal":{"name":"Hypoxia (Auckland, N.Z.)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2018-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2147/HP.S165092","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36188779","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}