Short-Term Hemodynamic Effects of Apelin in Patients With Pulmonary Arterial Hypertension

Abstract

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).

Keywords: APJ; CO, cardiac output; FA, formic acid; NO, nitric oxide; PAEC, pulmonary artery endothelial cells; PAH, pulmonary arterial hypertension; PDE5, phosphodiesterase-5; PVR, pulmonary vascular resistance; SVR, systemic vascular resistance; apelin; human; pulmonary arterial hypertension.

Figures

Graphical abstract

Figure 1

Hemodynamic Changes During Apelin Infusion in Patients With PAH Hemodynamic changes during infusion of (Pyr1)apelin-13 (solid squares) or matched saline placebo (open squares) in patients with pulmonary arterial hypertension (PAH) in pulmonary vascular resistance (PVR), cardiac output, mean pulmonary artery pressure (mPAP), heart rate, systemic vascular resistance (SVR), and mean arterial pressure (MAP). Data are reported as mean ± SEM. *p = 0.0089, **p = 0.002, ***p < 0.0006, §p = 0.0001, and #p ≤ 0.0001 2-way analysis of variance with post hoc Bonferroni tests. bpm = beats per minute.

Figure 2

Effect of Apelin and Exercise on PVR Pulmonary vascular resistance during infusion of (Pyr1)apelin-13 or matched saline placebo in patients with pulmonary arterial hypertension while undergoing exercise protocol. A zero reflects resting measurements, raise reflects measurements taken with legs raised in ergometers pedals at rest, then further measurements at 20% and 40% of previous erect maximal cardiopulmonary exercise test performance. Data are reported as mean ± SEM. *p = 0.019, 2-way analysis of variance with post hoc Bonferroni tests. PVR = pulmonary vascular resistance.

Figure 3

Patients With or Without PDE5 Inhibitor Treatment Hemodynamic changes during infusion of (Pyr1)apelin-13 (solid squares) or matched saline placebo (open squares) in patients with pulmonary arterial hypertension who are (A) on treatment with PDE5 inhibitors or (B) not on treatment with PDE5 inhibitors. Data are reported as mean ± SEM. *p = 0.049, **p = 0.0127, *** p = 0.0042, §p = 0.0039, §§p = 0.0017, #p = 0.0011, ##p = 0.0003, 2-way analysis of variance with post hoc Bonferroni tests. Abbreviations as in Figure 1.