hexarelin and Cardiomyopathy--Dilated

Growth hormone releasing peptides (GHRPs) are synthetic molecules endowed with potent neuroendocrine activities mediated by specific receptors in the pituitary and in the central nervous system. GHRPs receptors have been reported even in perpheral tissues, particularly in the myocardium, where they probably mediate growth hormone (GH)-independent activities. We studied in humans the cardiac effects of hexarelin administration in 7 normal adults, in 7 severe GH-deficient patients, and in 12 patients with severe dilated cardiomyopathy. Left ventricular ejection fraction (LVEF), mean blood pressure (MBP), heart rate (HR), and GH levels were evaluated at baseline and every 15 min up to 60 min after acute 2.0 microg/kg iv hexarelin administration. Basal LVEF in dilated cardiomyopathy was impaired and lower (p < 0.001) than in GH deficiency, in turn lower (p< 0.001) than in normal subjects. Hexarelin signficantly (p < 0.05) increased LVEF in normal and in GH-deficient subjects, but not in dilated cardiomyopathy, without significant variations in MBP and HR. Hexeralin significantly (p < 0.05) increased GH levels in normal subjects and in dilated cardiomyopathy but not in GH deficiency. These findings suggest that, in humans, the acute administration of hexarelin exerts a GH-independent positive inotropic effect likely mediated by specific GHRPs myocardial receptors.

Topics: Adult; Blood Pressure; Cardiomyopathy, Dilated; Cardiomyopathy, Hypertrophic; Growth Hormone; Heart; Heart Rate; Hormones; Humans; Myocardium; Oligopeptides; Radionuclide Imaging; Stroke Volume

To investigate acute cardiotropic activities of hexarelin in patients with severe left ventricular dysfunction due to ischemic (iCMP) and dilated cardiomyopathy (dCMP).. We studied the effect of intravenous hexarelin administration on growth hormone (GH) levels and left ventricular ejection fraction (LVEF) evaluated by radionuclide angiography in eight patients with dCMP (age 53.0+/-2.8, LVEF 16.7+/-2.1%) and five patients with iCMP (age 52.0+/-2.8 years, LVEF 22.6+/-2.1). Results were compared with a group of seven normal subjects (age 37.4+/-3.4 years, LVEF 64.0+/-1.5%) and seven patients with severe growth-hormone deficiency (GHD; age 42.0+/-4.4 years, LVEF 50.0+/-1.9%) previously studied with the same methodology. In dCMP and iCMP patients hexarelin induced a similar significant (P<0.05) increase in GH levels. In iCMP patients hexarelin induced a LVEF increase (peak LVEF 26.2+/-2.5%, P<0.05) as observed in normals and GHD, while in dCMP LVEF was unchanged (peak LVEF 17.7+/-1.7, P=NS). In all groups other hemodynamic parameters were unchanged.. Acute hexarelin administration increases LVEF in iCMP patients (as in normals and GHD) but not in dCMP patients in spite of a similar GH releasing effect and basal LVEF. A possible explanation of the positive inotropic effect of hexarelin in iCMP could be a direct stimulation on viable myocardium or myocardial contractile reserve.

Topics: Adult; Cardiomyopathy, Dilated; Hemodynamics; Human Growth Hormone; Humans; Middle Aged; Myocardial Ischemia; Oligopeptides; Severity of Illness Index; Statistics as Topic; Stroke Volume; Time Factors; Ventricular Dysfunction, Left

Topics: Cardiomyopathy, Dilated; Case-Control Studies; Clinical Trials as Topic; Growth Hormone; Growth Hormone-Releasing Hormone; Heart Ventricles; Humans; Insulin-Like Growth Factor I; Oligopeptides

There is evidence showing that GH and IGF-I have specific receptors in the heart and that these hormones are able to promote cardiac remodelling and inotropism. It has been reported that patients with dilated cardiomyopathy (DCM) benefit from treatment with rhGH showing a striking increase in cardiac contractility. However, until now, the activity of GH/IGF-I axis in DCM has never been clearly assessed.. To clarify this point, we enrolled 39 patients with idiopathic or post-ischaemic DCM (36 M/3 F; age (mean +/- S.D.) 55.3 +/- 9.0 years; BMI: 25.3 +/- 3.2 kg/m2; New York Heart Association class (NYHA) I/2, II/19, III/15, IV/3) and 42 age-matched controls (CS, 38 M/4 F; age 56.0 +/- 7.8 years; BMI: 24.9 +/- 1.5 kg/m2). DCM patients were characterized by a left-ventricular diastolic diameter of 73.8 +/- 8.3 mm, a shortening fraction of 15.9 +/- 6.4% and a left ventricular ejection fraction of 25.1 +/- 8.7%. In all subjects clinical and biochemical indices of renal and hepatic function as well as nutritional parameters were in the normal range.. In both groups we studied: a) IGF-I levels in basal conditions and after administration of low rhGH doses for 4 days (5.0 or 10.0 mu/kg/day x 4 days); b) the acute GH-response to GHRH (1.0 mu/kg i.v.) or hexarelin (HEX, 2.0 mu/kg i.v.), a peptidyl GH secretagogue (GHRP); c) mean GH concentration (mGHc) over 10 h sampling (every 20 min) from 2200 h to 0800 h.. Basal IGF-I levels in DCM were lower (P = 0.000039) than in CS (135.2 +/- 46.8 vs. 193.7 +/- 63.7 mu/l), whereas, basal IGFBP-3 and GHBP2 levels in DCM and CS were similar (2.5 +/- 1.3 vs. 2.6 +/- 0.5 mg/l and 25.3 +/- 3.6 vs. 28.3 +/- 5.0%; P = 0.95 and P = 0.085, respectively). After 4 days of 5.0 mu/kg/day rhGH administration, IGF-I levels in DCM (215.4 +/- 82.0 mu/l; P = 0.0023 vs. baseline) remained lower (P = 0.027) than those in CS (280.0 +/- 80.7 mu/l; P = 0.000080 vs. baseline). After 10.0 mu/kg/day for 4 days, IGF-I levels in DCM (297.2 +/- 109.2 mu/l; P = 0.0033 vs. baseline) were similar (P = 0.76) to those in CS (310.9 +/- 81.7 mu/l; P = 0.000060 vs. baseline). The GH response to GHRH in DCM was lower (P = 0.0022) than that in CS (hAUC0-120: 192.0 +/- 177.3 vs. 345.3 +/- 191.1 mu/l/h) whereas that to HEX in DCM and CS was similar (611.0 +/- 437.5 vs. 535.4 +/- 302.8 mu/l/h; P = 0.95). Within the DCM group, basal and rhGH-stimulated IGF-levels as wel as the GH response to GHRH or HEX were not different among NYHA classes and did not show any correlation with ECHO parameters. The mGHc in DCM (1.0 +/- 0.5 mu/l) was similar (P = 0.57) to that in CS (0.9 = 0.7 mu/l).. Our present data demonstrate that in dilated cardiomyopathy patients with severe left ventricular dysfunction basal IGF-I levels are reduced whereas the IGF-I response to low rhGH doses is preserved. These findings suggest a normal peripheral GH sensitivity in dilated cardiomyopathy. On the other hand, though nocturnal mean GH concentration in dilated cardiomyopathy patients is similar to that in normal subjects, the somatotroph responsiveness to GHRH, but not that to hexarelin, is reduced. Thus, subtle alterations in the activity of GH/IGF-I axis are present in dilated cardiomyopathy.

Topics: Cardiomyopathy, Dilated; Case-Control Studies; Female; Growth Hormone; Growth Hormone-Releasing Hormone; Humans; Insulin-Like Growth Factor I; Male; Middle Aged; Oligopeptides

Topics: Arginine; Cardiomyopathy, Dilated; Drug Combinations; Growth Hormone-Releasing Hormone; Human Growth Hormone; Humans; Insulin-Like Growth Factor I; Middle Aged; Oligopeptides; Reference Values