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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
DOUBLE
Enrollment
63
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.
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.
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.
Royal Infirmary Edinburgh
Edinburgh, United Kingdom
RECRUITINGGolden Jubilee National Hospital
Glasgow, United Kingdom
RECRUITINGHammersmith Hospital
London, United Kingdom
RECRUITINGChange in pulmonary vascular resistance
We will measure the change in pulmonary vascular resistance after infusion of Apelin during right heart catheterisation
Time frame: 5,10,15 and 30 minutes after start of infusion
Change in systemic vascular resistance
We will measure the change in systemic vascular resistance during infusion of Apelin
Time frame: 5,10,15 and 30 minutes after start of infusion
Change in Cardiac Output
We will measure the change in cardiac output after infusion of Apelin during right heart catheterisation.
Time frame: 5,10,15 and 30 minutes after start of infusion
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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.