Abstract 4870: Cardiovascular Effects Of Apelin In Healthy Volunteers And Patients With Heart Failure
BACKGROUND Apelin is the most potent inotrope yet described. In preclinical models, it increases cardiac output in normal and failing hearts and lowers blood pressure through peripheral vasodilatation. We have recently demonstrated that apelin causes nitric oxide-dependent vasodilatation in man. Here, we aimed to establish the effects of apelin on cardiac and systemic hemodynamics variables.
METHODS All studies were performed in a randomized, double-blinded manner. Forearm blood flow responses to intrabrachial infusions of (Pyr1)apelin-13 (0.3–3 nmol/min), acetylcholine (5–20 μg/min) and sodium nitroprusside (SNP; 1– 4 μg/min) were measured by venous occlusion forearm plethysmography in 12 patients with stable chronic heart failure (CHF; NYHA class II–III) and 12 matched controls. Cardiac index (CI; assessed non-invasively by thoracic electrical bioimpedance) blood pressure and heart rate (HR) were measured during intravenous infusions of (Pyr1)apelin-13 (30 –300 nmol/min) and saline placebo in 6 patients with stable CHF and 7 matched controls. The maximum rate of pressure rise within the left ventricle (dP/dt max) was measured in 4 patients following intracoronary boluses of apelin-36 (20 and 200 nmol) and saline placebo.
RESULTS Apelin infusions were well tolerated with no reported symptoms or ECG abnormalties. Apelin, acetylcholine and SNP caused vasodilatation in forearm resistance vessels of both CHF patients and controls (all p<0.0001). Responses to acetylcholine (P=0.01) but not apelin (p=0.3) or SNP (p=0.9) were diminished in patients with CHF compared with controls. In CHF patients, apelin increased cardiac index by 16% (p<0.05) and lowered mean arterial pressure (MAP) by 7% (p<0.05) but had no effect on HR (p=0.17). In controls, apelin increased CI by 8% (p<0.05) and HR by 13% (p<0.01) and lowered MAP by 8% (P<0.01). Intracoronary injection of apelin appeared to increase cardiac contractility (dP/dt max rise of 8%, p=0.056).
CONCLUSIONS Apelin increases cardiac output and lowers blood pressure in man, through both peripheral arteriolar vasodilatation and increased cardiac contractility. These effects of apelin are preserved in patients with CHF suggesting a potential therapeutic role for apelin agonism in heart failure.