Author + information
- Received October 23, 2017
- Revision received December 2, 2017
- Accepted January 13, 2018
- Published online April 30, 2018.
- Lauren Brash, MDa,
- Gareth D. Barnes, MDc,
- Melanie J. Brewis, MDa,
- A. Colin Church, MDa,
- Simon J. Gibbs, MDc,
- Luke S.G.E. Howard, MDc,
- Geeshath Jayasekera, MBChBa,
- Martin K. Johnson, MDa,
- Neil McGlinchey, MBChBa,
- Joelle Onorato, PhDd,
- Joanne Simpson, MDa,
- Colin Stirrat, MDb,
- Stephen Thomson, MBChBa,
- Geoffrey Watson, MDc,
- Martin R. Wilkins, MDc,
- Carrie Xu, MSd,
- David J. Welsh, PhDa,
- David E. Newby, MDb and
- Andrew J. Peacock, MDa,∗ ()
- aScottish Pulmonary Vascular Unit, Golden Jubilee National Hospital, Glasgow, United Kingdom
- bBritish Heart Foundation/University of Edinburgh Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, United Kingdom
- cNational Pulmonary Hypertension Service–London, Department of Cardiac Sciences, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, United Kingdom
- dBristol-Myers Squibb Company, Discovery R&D, Princeton, New Jersey
- ↵∗Address for correspondence:
Prof. Andrew J. Peacock, Scottish Pulmonary Vascular Unit, Golden Jubilee National Hospital, Agamemnon Street, Glasgow G81 4DY, United Kingdom.
• The effects of apelin on pulmonary hemodynamics in patients with PAH are unknown.
• Systemic infusion caused a significant reduction in pulmonary vascular resistance and increase in cardiac output without a change in heart rate or systemic vascular resistance.
• This effect was most prominent in the subgroup of patients receiving concomitant PDE5 inhibition.
• Apelin agonism is a novel potential therapeutic target for PAH.
Apelin agonism causes systemic vasodilatation and increased cardiac contractility in humans, and improves pulmonary arterial hypertension (PAH) in animal models. Here, the authors examined the short-term pulmonary hemodynamic effects of systemic apelin infusion in patients with PAH. In a double-blind randomized crossover study, 19 patients with PAH received intravenous (Pyr1)apelin-13 and matched saline placebo during invasive right heart catheterization. (Pyr1)apelin-13 infusion caused a reduction in pulmonary vascular resistance and increased cardiac output. This effect was accentuated in the subgroup of patients receiving concomitant phosphodiesterase type 5 inhibition. Apelin agonism is a novel potential therapeutic target for PAH. (Effects of Apelin on the Lung Circulation in Pulmonary Hypertension; NCT01457170)
Funding for this clinical study was provided by a British Heart Foundation Project Grant (PG/11/113/29280). Dr. Newby (CH/09/002) is supported by the British Heart Foundation; and is the recipient of a Wellcome Trust Senior Investigator Award (WT103782AIA). Dr. Gibbs has served on Speakers Bureau for Actelion, Bayer, Merck Sharp and Dohme, and GlaxoSmithKline; has served on advisory boards for Actelion, Bayer, and Arena; has been a consultant for Actelion, Pfizer, and Bellepheron; and has received honoraria and/or fees from Bayer, Merck Sharp and Dohme, Pfizer, Arena, Bellepheron, and GlaxoSmithKline. Dr. Johnson has received research grants, funding to attend meetings, and speaker honoraria from Actelion, Merck Sharp and Dohme, and Bayer. Dr. Onorato is an employee of Bristol-Myers Squibb. Prof. Peacock has received honoraria, travel assistance, and research support from Actelion, Arena, Bayer, GlaxoSmithKline, Merck Sharp and Dohme, and United Therapeutics. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
All authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the JACC: Basic to Translational Science author instructions page.
- Received October 23, 2017.
- Revision received December 2, 2017.
- Accepted January 13, 2018.
- 2018 The Authors