Effects of acute hexarelin administration on cardiac performance in patients with coronary artery disease during by-pass surgery

Abstract

Growth hormone (GH) secretagogues are synthetic molecules with neuroendocrine but also cardiovascular activities mediated by specific GH secretagogue-receptors. The acute administration of hexarelin, a peptidyl GH secretagogue, increases left ventricular ejection fraction in normal subjects and even in patients with severe GH deficiency. We evaluated cardiac performances in patients with coronary artery disease after acute administration of hexarelin (2.0 μg/kg, i.v.) compared to that in patients given with GH-releasing hormone (GHRH; 2.0 μg/kg, i.v.), recombinant human (rh)-GH (10.0 μg/kg, i.v.) or placebo. Cardiac performance was studied in 24 male patients (age [mean±S.E.M.]: 59.5±1.1 years; body mass index: 24.6±0.9 kg/m 2; left ventricular ejection fraction: 57.2±1.4%) with coronary artery disease undergoing by-pass surgery during general anesthesia. Left ventricular ejection fraction, left ventricular end diastolic volume, cardiac index and cardiac output were evaluated by intraoperative omniplane transoesophageal echocardiography while wedge pressure, central venous pressure, mean arterial pressure and systemic vascular resistance index were evaluated by systemic and pulmonary arterial catheterization. RhGH, GHRH and placebo did not exert any hemodynamic effect while hexarelin induced a prompt (after +10 min) increase in left ventricular ejection fraction ( P<0.001), cardiac index ( P<0.001) and cardiac output ( P<0.001) lasting up to +90 min without any variation in left ventricular end diastolic volume. Accordingly, hexarelin induced a reduction of wedge pressure ( P<0.01). These changes occurred in the presence of increased mean arterial pressure ( P<0.05) and transient decrease of central venous pressure ( P<0.05 at +30 min only) but no change in systemic vascular resistance index. Heart rate after hexarelin was similar to that after placebo. Hexarelin induced a slight increase in GH levels which was similar to that after GHRH but far lower ( P<0.01) than that after rhGH. Thus, in patients with coronary artery disease undergoing by-pass surgery, the acute administration of hexarelin clearly improves cardiac performance without any relevant variation in systemic vascular resistance. The cardiotropic effect of hexarelin is not shared by GHRH or by rhGH, indicating that it is not mediated by the increase in circulating GH levels but more likely reflects activation of specific cardiovascular GH secretagogue receptors.