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The PEGASUS study is the first multicentric and prospective assessment of the safety of air travel flying in pulmonary hypertension (PH) (NCT03051763). Data of air travel from 60 patients with PH was available. No severe adverse events occurred. Nine patients self-reported mild adverse events during flight (13%), while after landing, 12 patients reported events (20%). Solely one patient (2%) had an adverse event leading to medical consultation. In patients with PH and World Health Organization functional classes II and III, air travel was safe., Competing Interests: Henning Gall reports grants from the German Research Foundation and nonfinancial support from the University of Giessen during the conduct of the study, and personal fees from Actelion, AstraZeneca, Bayer, BMS, GSK, Janssen‐Cilag, Lilly, MSD, Novartis, OMT, Pfizer, and United Therapeutics outside the submitted work. Athiththan Yogeswaran reports non‐financialnonfinancial support from the University of Giessen during the conduct of the study. Natascha Sommer reports personal fees from Actelion outside the submitted work. Hossein A. Ghofrani reports grants from the German Research Foundation and nonfinancial support from the University of Giessen during the conduct of the study, and personal fees from Bayer, Actelion, Pfizer, Merck, GSK, and Takeda, grants and personal fees from Novartis, Bayer HealthCare, and Encysive/Pfizer, and grants from Aires, the German Research Foundation, Excellence Cluster Cardiopulmonary Research, and the German Ministry for Education and Research outside the submitted work. Werner Seeger reports grants from the German Research Foundation and nonfinancial support from the University of Giessen during the conduct of the study, and personal fees from Pfizer and Bayer Pharma AG outside the submitted work. Manuel J. Richter reports grants from the German Research Foundation and nonfinancial support from the University of Giessen during the conduct of the study, and grants from United Therapeutics, grants and personal fees from Bayer, and personal fees from Actelion, Mundipharma, Roche, and OMT outside the submitted work. Khodr Tello reports grants from the German Research Foundation and nonfinancial support from the University of Giessen during the conduct of the study, and personal fees from Actelion and Bayer outside the submitted work. Heinrike Wilkens received fees for lectures and/or consultations from Actelion, AOP, Bayer, Biotest, Boehringer‐Ingelheim, Daiichi Sankyo, Ferrer, GSK, Janssen Cilag, and MSD outside the submitted work. Michael Halank reports personal fees from AstraZeneca, Janssen‐Cilag, and MSD outside the submitted work. Melanie Heberling reports personal fees from Janssen‐Cilag und MSD outside the submitted work. Dr. Ulrich receives research grants from the Swiss National Science Foundation, Zurich and Swiss Lung League, Orpha‐Swiss, Emdo Foundation and travel support, lecture fees, and advisory compensation from MSD SA, Orpha Swiss, Janssen SA, Novartis SA, all unrelated to the present work. Katrin Milger reports speaker and/or advisory board honoraria from AOP Pharma, Ferrer, Janssen, MSD. Tobias J. Lange reports personal fees from Acceleron Pharma, AstraZeneca, Bayer, Böhringer Ingelheim, Ferrer, Gossamer Bio, Janssen Cilag, MSD, Orphacare, and Pfizer. Stefan Stadler reports personal fees from Acceleron Pharma, AOP Health, Gossamer Bio, Janssen Cilag, MSD, and Pfizer. Jan C. Kamp is supported by PRACTIS—Clinician Scientist Program of Hannover Medical School, funded by the German Research Foundation, grant no. ME 3696/3‐1, KFO311— 286251789. Ekkehard Grünig has received fees for lectures and/or consultations from Actelion, Bayer/MSD, Ferrer, GEBRO, GSK, Janssen, and OMT. Research grants to his institution have been received from Acceleron, Actelion, BayerHealthCare, MSD, Bellerophon, GossamerBio, GSK, Janssen, Novartis, OMT, Pfizer, REATE, and United Therapeutics outside the submitted work. Satenik Harutynova has received support from Janssen, OMT, Bayer Pharma, GSK and speaker fees from Janssen and OMT outside submitted work. Karen Olsson has received fees for lectures and/or consultations from Acceleron, Actelion, AOP, MSD, Ferrer, Janssen, and OMT. Research grants to her institution have been received from Actelion, all outside the submitted work. All other authors declare no conflicts of interest., (© 2024 The Author(s). Pulmonary Circulation published by John Wiley & Sons Ltd on behalf of Pulmonary Vascular Research Institute.)

Background and Purpose: Chronic obstructive pulmonary disease, encompassing chronic airway obstruction and lung emphysema, is a major worldwide health problem and a severe socio-economic burden. Evidence previously provided by our group has shown that inhibition of inducible NOS (iNOS) prevents development of mild emphysema in a mouse model of chronic tobacco smoke exposure and can even trigger lung regeneration. Moreover, we could demonstrate that pulmonary hypertension is not only abolished in cigarette smoke-exposed iNOS -/- mice but also precedes emphysema development. Possible regenerative effects of pharmacological iNOS inhibition in more severe models of emphysema not dependent on tobacco smoke, however, are hitherto unknown., Experimental Approach: We have established a mouse model using a single dose of porcine pancreatic elastase or saline, intratracheally instilled in C57BL/6J mice. Emphysema, as well as pulmonary hypertension development was determined by both structural and functional measurements., Key Results: Our data revealed that (i) emphysema is fully established after 21 days, with the same degree of emphysema after 21 and 28 days post instillation, (ii) emphysema is stable for at least 12 weeks and (iii) pulmonary hypertension is evident, in contrast to smoke models, only after emphysema development. Oral treatment with the iNOS inhibitor N(6)-(1-iminoethyl)-l-lysine (L-NIL) was started after emphysema establishment and continued for 12 weeks. This resulted in significant lung regeneration, evident in the improvement of emphysema and reversal of pulmonary hypertension., Conclusion and Implications: Our data indicate that iNOS is a potential new therapeutic target to treat severe emphysema and associated pulmonary hypertension., Linked Articles: This article is part of a themed issue on Risk factors, comorbidities, and comedications in cardioprotection. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.1/issuetoc., (© 2020 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Therapeutic options for pulmonary arterial hypertension (PAH) have increased over the last decades. The advent of pharmacological therapies targeting the prostacyclin, endothelin, and NO pathways has significantly improved outcomes. However, for the vast majority of patients, PAH remains a life-limiting illness with no prospect of cure. PAH is characterised by pulmonary vascular remodelling. Current research focusses on targeting the underlying pathways of aberrant proliferation, migration, and apoptosis. Despite success in preclinical models, using a plethora of novel approaches targeting cellular GPCRs, ion channels, metabolism, epigenetics, growth factor receptors, transcription factors, and inflammation, successful transfer to human disease with positive outcomes in clinical trials is limited. This review provides an overview of novel targets addressed by clinical trials and gives an outlook on novel preclinical perspectives in PAH. LINKED ARTICLES: This article is part of a themed issue on Risk factors, comorbidities, and comedications in cardioprotection. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.1/issuetoc., (© 2020 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Background: Sepsis is a severe inflammatory disorder with a high mortality in intensive care units mostly due to multiorgan failure. Mitochondrial dysfunction is regarded as a key factor involved in the pathogenesis of septic disorders, leading to a decline in energy supply. The aim of the present study was to evaluate whether application of short-chain fatty acids (SCFAs) and medium-chain fatty acids (MCFAs) could improve mitochondrial function and thus might serve as a potential energy source under inflammatory conditions., Materials and Methods: As an experimental approach, starved human endothelial cells and monocytes were incubated with hexanoic acid, heptanoic acid, octanoic acid, or glucose and subsequently subjected to high-resolution respirometry to assess mitochondrial function under baseline conditions. In a second set of experiments, cells were pretreated with tumor necrosis factor-α to mimic inflammation and sepsis., Results: We demonstrated that addition of SCFAs and MCFAs increases mitochondrial respiratory capacity at baseline and inflammatory conditions in both cell types. None of the fatty acids induced changes in mitochondrial DNA content or the generation of proinflammatory cytokines, indicating a beneficial safety profile., Conclusion: We deduce that SCFAs and MCFAs are suitable and safe sources of energy under inflammatory conditions with the capability to partly restore mitochondrial respiration., (© 2013 American Society for Parenteral and Enteral Nutrition.)