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| Name | Class |
|---|---|
| NHS Lothian | OTHER_GOV |
| Imperial College Healthcare NHS Trust | OTHER |
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The purpose of this study is to determine the effects of Apelin on the lung circulation. The investigators hypothesise that Apelin will relax the lung blood vessels and improve the pumping ability of the heart.
Apelin is an endogenous peptide with physiological actions in the cardiovascular system and is abundantly expressed in the pulmonary vasculature. Pre-clinical models and preliminary clinical data indicate that Apelin deficiency may mediate or contribute to the pathogenesis of pulmonary hypertension and heart failure. Apelin causes peripheral vasodilatation and increased cardiac contractility. The investigators will determine the effects of Apelin on the pulmonary circulation in 3 groups; healthy control, people with pulmonary arterial hypertension and people with pulmonary hypertension due to heart failure. Each subject will receive both Apelin infusion and saline placebo infusion in a crossover design. The infusions will be given in a random order which the subject and the investigator will be blinded to. The investigators hypothesise that Apelin will have more marked pulmonary haemodynamic effects than that observed in the systemic circulation. Moreover, the investigators propose that Apelin will have a marked vasodilatory effect on the human pulmonary vasculature and reduce pulmonary vascular resistance in patients with pulmonary arterial hypertension or pulmonary hypertension due to left heart disease.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Apelin/Saline | Experimental | Apelin infusion then crossover to Saline infusion |
|
| Saline/Apelin | Experimental | Saline infusion then crossover to Apelin infusion |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Apelin | Drug | During right heart catheterisation, Apelin will be infused at 30, 100 and 300 nanomol/min for 5 minutes. Apelin will then be infused at 300 nanomol/min for a further 15 minutes while the subject exercises using a supine ergometer. |
| Measure | Description | Time Frame |
|---|---|---|
| Change in pulmonary vascular resistance | We will measure the change in pulmonary vascular resistance after infusion of Apelin during right heart catheterisation | 5,10,15 and 30 minutes after start of infusion |
| Measure | Description | Time Frame |
|---|---|---|
| Change in systemic vascular resistance | We will measure the change in systemic vascular resistance during infusion of Apelin | 5,10,15 and 30 minutes after start of infusion |
| Change in Cardiac Output |
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PULMONARY ARTERIAL HYPERTENSION
Inclusion Criteria:
Exclusion Criteria:
HEART FAILURE
Inclusion Criteria:
HEALTHY VOLUNTEERS
Inclusion Criteria:
Exclusion Criteria:
ALL SUBJECTS
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Andrew J Peacock, BSc MPhil MD | Contact | +44 (0)141 951 5497 | apeacock@udcf.gla.ac.uk | |
| Lauren Brash, MBChB | Contact | +44 (0)7738569980 | laurenbrash@nhs.net |
| Name | Affiliation | Role |
|---|---|---|
| Andrew J Peacock, BSc MPhil MD | National Health Service: Golden Jubilee National Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Royal Infirmary Edinburgh | Recruiting | Edinburgh | EH16 4SA | United Kingdom |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29876530 | Derived | Brash L, Barnes GD, Brewis MJ, Church AC, Gibbs SJ, Howard LSGE, Jayasekera G, Johnson MK, McGlinchey N, Onorato J, Simpson J, Stirrat C, Thomson S, Watson G, Wilkins MR, Xu C, Welsh DJ, Newby DE, Peacock AJ. Short-Term Hemodynamic Effects of Apelin in Patients With Pulmonary Arterial Hypertension. JACC Basic Transl Sci. 2018 Mar 28;3(2):176-186. doi: 10.1016/j.jacbts.2018.01.013. eCollection 2018 Apr. |
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| ID | Term |
|---|---|
| D000081029 | Pulmonary Arterial Hypertension |
| D006333 | Heart Failure |
| D006976 | Hypertension, Pulmonary |
| ID | Term |
|---|---|
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
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| ID | Term |
|---|---|
| D000073861 | Apelin |
| D012965 | Sodium Chloride |
| ID | Term |
|---|---|
| D036341 | Intercellular Signaling Peptides and Proteins |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D001685 | Biological Factors |
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| Saline (Placebo) | Drug | During right heart catheterisation, saline will be infused for 15 minutes while the subject rest and for a further 15 minutes while the subject exercises using a supine ergometer. |
|
| Saline (Placebo) | Drug | During right heart catheterisation, saline will be infused for 15 minutes while the subject rest and for a further 15 minutes while the subject exercises using a supine ergometer. |
|
| Apelin | Drug | During right heart catheterisation, Apelin will be infused at 30, 100 and 300 nanomol/min for 5 minutes. Apelin will then be infused at 300 nanomol/min for a further 15 minutes while the subject exercises using a supine ergometer. |
|
We will measure the change in cardiac output after infusion of Apelin during right heart catheterisation.
| 5,10,15 and 30 minutes after start of infusion |
| Golden Jubilee National Hospital | Recruiting | Glasgow | G81 4HX | United Kingdom |
|
| Hammersmith Hospital | Recruiting | London | W12 0HS | United Kingdom |
|
| D006973 |
| Hypertension |
| D014652 | Vascular Diseases |
| D002712 | Chlorides |
| D006851 | Hydrochloric Acid |
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
| D017670 | Sodium Compounds |