Pulmonary hypertension最新文献_第8页

Pulmonary Veno-occlusive Disease and Pulmonary Capillary Hemangiomatosis 肺静脉闭塞性疾病和肺毛细血管瘤病

Pulmonary hypertension Pub Date : 2020-01-01 DOI: 10.1007/978-3-030-52787-7_6

B. Levarge, D. Montani, M. Humbert

引用次数: 0

Sarcoidosis-Associated Pulmonary Hypertension 结节病相关性肺动脉高压

Pulmonary hypertension Pub Date : 2020-01-01 DOI: 10.1007/978-3-030-52787-7_9

H. Ford, Ahmed Sesay, E. Sonntag, S. Krishnan

引用次数: 0

Caspase-1 triggers smooth muscle cell proliferation in hypoxic pulmonary hypertension Caspase-1触发缺氧肺动脉高压平滑肌细胞增殖

Pulmonary hypertension Pub Date : 2019-09-28 DOI: 10.1183/13993003.congress-2019.pa5049

Camilla Udjus, B. Halvorsen, P. Aukrust, G. Christensen, O. Skjønsberg, K. Larsen

{"title":"Caspase-1 triggers smooth muscle cell proliferation in hypoxic pulmonary hypertension","authors":"Camilla Udjus, B. Halvorsen, P. Aukrust, G. Christensen, O. Skjønsberg, K. Larsen","doi":"10.1183/13993003.congress-2019.pa5049","DOIUrl":"https://doi.org/10.1183/13993003.congress-2019.pa5049","url":null,"abstract":"Background: Pulmonary hypertension is a serious complication to chronic lung diseases, often with alveolar hypoxia. Mechanisms for hypoxia-induced pulmonary hypertension are suggested to be initial vasoconstriction, followed by inflammation, proliferation of smooth muscle cells (SMCs) and fibrosis in pulmonary arteries. Elevated levels of Interleukin (IL)-18, IL-1β and IL-6 are found in patients with pulmonary hypertension. IL-18 and IL-1β are proinflammatory cytokines activated by the enzyme caspase-1. We have documented that caspase-1 deficient mice have reduced hypoxia-induced pulmonary hypertension and reduced muscularization in pulmonary arteries compared to wild-type (WT) mice. Objective: To study mechanisms of SMC proliferation in hypoxic pulmonary hypertension initiated by the enzyme caspase-1. Methods: Pulmonary arteries from WT and caspase-1-/- mice were harvested and grown “ex vivo”. Human SMCs were exposed to hypoxia and treated with caspase-1 inhibitor. Proliferation of SMCs was measured by cell count, BrdU incorporation, Ki67 and cyclin D1 mRNA. Results: Caspase-1 abrogated arteries showed reduced SMC proliferation, together with lowered levels of IL-18, IL-1β and IL-6. Supply of IL-18 or IL-1β rescued SMC proliferation in caspase-1 deficient arteries, and the level of IL-6 protein was restored. Hypoxic stimulation of human SMCs showed increased BrdU incorporation and Ki67 protein levels, indicating hypoxia-induced cell proliferation. Cell count, BrdU incorporation and cyclin D1 mRNA levels were reduced by adding a caspase-1 inhibitor. Conclusions: The enzyme caspase-1 regulates smooth muscle cell proliferation through IL-18/IL-1β and IL-6, being novel targets in pulmonary hypertension.","PeriodicalId":20724,"journal":{"name":"Pulmonary hypertension","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74424545","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}

引用次数: 0

A phase 1, single-center, open-label, dose-rising clinical trial to evaluate the pharmacokinetics, safety and tolerability of treprostinil inhalation powder (TreT) in healthy normal volunteers 一项1期、单中心、开放标签、剂量递增的临床试验，旨在评估TreT在健康正常志愿者体内的药代动力学、安全性和耐受性

Pulmonary hypertension Pub Date : 2019-09-28 DOI: 10.1183/13993003.congress-2019.pa4749

Peter Smith, C. Watkins, K. Kraft, M. Grant

{"title":"A phase 1, single-center, open-label, dose-rising clinical trial to evaluate the pharmacokinetics, safety and tolerability of treprostinil inhalation powder (TreT) in healthy normal volunteers","authors":"Peter Smith, C. Watkins, K. Kraft, M. Grant","doi":"10.1183/13993003.congress-2019.pa4749","DOIUrl":"https://doi.org/10.1183/13993003.congress-2019.pa4749","url":null,"abstract":"Rationale: United Therapeutics is developing a new drug-device product comprising a dry powder formulation of treprostinil inhalation powder (TreT) and a small, portable, dry powder inhaler, to treat pulmonary arterial hypertension (PAH). Objectives: The primary objective was to evaluate the pharmacokinetics (PK), safety and tolerability of TreT in healthy normal volunteers (HNVs). Methods: This was an open-label, single ascending dose study in 36 HNVs, assigned to 6 single dose cohorts of TreT (30, 60, 90, 120, 150, and 180 µg). Safety and tolerability of TreT was evaluated in each cohort prior to escalating the dose for the next cohort. Blood samples were obtained before TreT administration and at selected times through 480 minutes post‑dose. Blood samples were analyzed for treprostinil using a validated analytical method and PK parameters were calculated using noncompartmental methods. Results: A total of 36 HNVs were randomized and dosed. There were no severe adverse events (AEs), serious AEs, or deaths during the study. No AEs led to a subject’s early termination. The most frequently reported AEs were cough (n=11, 30.6%) and headache (n=8, 22.2%). Bioanalysis confirmed that the treprostinil plasma concentrations and exposure for TreT, achieved clinically relevant concentrations comparable to those observed in historical Tyvaso single dose clinical studies. Cmax and AUC for treprostinil, increased in a linear manner with increasing dose. Conclusion: Overall, TreT was safe and well-tolerated and produced clinically relevant concentrations of treprostinil when inhaled as a dry powder.","PeriodicalId":20724,"journal":{"name":"Pulmonary hypertension","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77272447","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}

引用次数: 2

A prospective study comparing the repeatability and sensitivity to change of non-invasive endpoints in pulmonary arterial hypertension: the RESPIRE study 一项前瞻性研究比较肺动脉高压无创终点变化的可重复性和敏感性:呼吸研究

Pulmonary hypertension Pub Date : 2019-09-28 DOI: 10.1183/13993003.congress-2019.oa496

D. Kiely, A. Swift, Marcella Cogliano, L. Kendall, C. Oram, D. Capener, A. Rothman, P. Garg, C. Johns, M. Austin, J. Pickworth, P. Hickey, Tony Kahn, A. Lawrie, R. Condliffe, Fred Wilson, J. Wild

引用次数: 2

Right ventricular-arterial coupling in chronic thromboembolic pulmonary hypertension patients during exercise 慢性血栓栓塞性肺动脉高压患者运动时的右心室-动脉耦合

Pulmonary hypertension Pub Date : 2019-09-28 DOI: 10.1183/13993003.congress-2019.pa1436

N. Braams, O. Spruijt, F. Oosterveer, B. Westerhof, A. Noordegraaf, L. Meijboom, F. S. D. Man, H. Bogaard

引用次数: 1

Role of vasoactive mediators on cigarette smoke extract (CSE)-induced proliferation in human pulmonary artery smooth muscle cells (hPASMCs) 血管活性介质对香烟提取物诱导的人肺动脉平滑肌细胞增殖的影响

Pulmonary hypertension Pub Date : 2019-09-28 DOI: 10.1183/13993003.congress-2019.pa1423

A. Alqarni, O. Brand, A. Pasini, Abdulrhman Alghamdi, Wael Alshehri, Mushabbab A Alahmari, L. Pang

引用次数: 1

Outcome of pulmonary thromboendarterectomy in chronic thromboembolic disease with normal hemodynamic: is it time to change the definition of CTEPH 正常血流动力学的慢性血栓栓塞性疾病肺血栓动脉内膜切除术的结果:是时候改变CTEPH的定义了吗

Pulmonary hypertension Pub Date : 2019-09-28 DOI: 10.1183/13993003.congress-2019.pa1439

F. Rashidi, R. Parvizi, Eisa Bilejani, Ata Koohi

引用次数: 0

Risk assessment and prognosis in patients with pulmonary arterial hypertension receiving intravenous treprostinil 静脉注射曲前列地尼肺动脉高压患者的风险评估及预后

Pulmonary hypertension Pub Date : 2019-09-28 DOI: 10.1183/13993003.congress-2019.oa499

K. Olsson, M. Richter, J. Kamp, H. Gall, A. Heine, H. Ghofrani, J. Fuge, R. Ewert, M. Hoeper

引用次数: 0

Therapeutic limitations of oral medications to normalize hemodynamics in patients with pulmonary artery hypertension 口服药物使肺动脉高压患者血流动力学正常化的治疗局限性

Pulmonary hypertension Pub Date : 2019-09-28 DOI: 10.1183/13993003.congress-2019.pa5467

H. Shimokawahara, H. Matsubara, K. Hayashi, T. Nishihara, M. Tsuji, T. Naito, M. Shigetoshi, I. Tabuchi, M. Munemasa

{"title":"Therapeutic limitations of oral medications to normalize hemodynamics in patients with pulmonary artery hypertension","authors":"H. Shimokawahara, H. Matsubara, K. Hayashi, T. Nishihara, M. Tsuji, T. Naito, M. Shigetoshi, I. Tabuchi, M. Munemasa","doi":"10.1183/13993003.congress-2019.pa5467","DOIUrl":"https://doi.org/10.1183/13993003.congress-2019.pa5467","url":null,"abstract":"Background: Pulmonary arterial hypertension (PAH) has a poor prognosis despite the available therapeutic options. Normalization of hemodynamics would be needed to obtain the good prognosis. Aims and Objectives: We aimed to investigate the determinants in PAH patients for normalization of hemodynamics only with oral drugs. Methods: We retrospectively reviewed 190 patients with PAH treated at a single referral center. Hemodynamic parameters were investigated before and after treatments. All the patients were divided into a good control group with mean pulmonary arterial pressure (mPAP)＜30mmHg and a poor control group with mPAP≧30mmHg at follow-up. Results: Eighty-two patients were idiopathic/heritable, 65 patients were connective tissue disease, 22 patients congenital heart disease and 21 patients were portal hypertension. mPAP decreased significantly from baseline to follow-up (51±18.7 mmHg to 34.1±15.2 mmHg, p Conclusions: To achieve normalization of hemodynamics in PAH, parenteral prostanoid should be used in cases with baseline mPAP exceeding 40mmHg.","PeriodicalId":20724,"journal":{"name":"Pulmonary hypertension","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90486343","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}

引用次数: 0