Radionuclide angiocardiographic evaluation of the cardiovascular effects of recombinant human IGF-I in normal adults

Objective: IGF-I possesses specific myocardial receptors and is able to promote cardiac remodelling and even inotropic effects in both humans and other animals. In fact, reduced cardiac mass and performance are present in GH deficiency and these alterations are counteracted by recombinant human (rh) GH replacement, restoring IGF-I levels. Recently, the acute administration of 60 mu g/kg rhIGF-I has also been reported to be able to improve cardiac performance evaluated by echocardiography or impedance cardiography in normal subjects. The aim of our study was to verify the effects of a subcutaneous low dose of rhIGF-I (20 mu g/kg) on cardiac performance in humans. Methods: In six healthy male adults (mean +/- S.E.M.: 35.7 +/- 4.3 years of age), the effects of rhIGF-I on left ventricular function evaluated by radionuclide angiocardiography and on circulating IGF-I, GH, insulin, glucose and catecholamines levels were studied. Results: Administration of rhIGF-I increased circulating IGF-I (peak at +150 min vs baseline: 330.2 +/- 9.6 vs 199.7 +/- 8.7 mu g/l, P < 0.03) to levels which persisted similarly up to +180 min. Neither GH nor catecholamine levels were modified by rhIGF-I administration, while insulin and glucose levels showed a slight but significant decrease. Basal left ventricular ejection fraction (61.8 +/- 2.0%) significantly increased at +180 min after rhIGF-I (65.3 +/- 2.7%, P < 0.03). No change was recorded in mean blood pressure while a non-significant trend towards a reduction of heart rate was present by +120 min. Conclusions: These findings indicate that even subcutaneous administration of a low dose of rhIGF-I has acute inotropic effects as evaluated by radionuclide angiocardiography in healthy adults

Acute cardiovascular and hormonal effects of GH and hexarelin, a synthetic GH-releasing peptide, in humans

Reduced cardiac mass and performances are present in GH deficiency and are counteracted by rhGH replacement. GH and IGF-I possess specific myocardial receptors and have been reported able to exert an acute inotropic effect. Synthetic GH secretagogues (GHS) possess specific pituitary and hypothalamic but even myocardial receptors. In 7 male volunteers, we studied cardiac performance by radionuclide angiocardiography after iv administration of rhGH or hexarelin (HEX), a peptidyl GHS. The administration of rhGH or HEX increased circulating GH levels to the same extent (AUC: 1594.6+/-88.1 vs 1739.3+/-262.2 mu g/l/min for 90 min) while aldosterone and catecholamine levels did not change; HEX, but not rhGH, significantly increased cortisol levels. Left ventricular ejection fraction (LVEF), mean blood pressure (MBP) and heart rate (HR) were unaffected by rhGH (62.4+/-2.1 vs 62.1+/-2.3%, 90.6+/-3.4 vs 92.0+/-2.5 mm Hg, 62.3+/-1.8 vs 66.7+/-2.7 bpm). HEX increased LVEF (70.7+/-3.0 vs 64.0+/-1.5%, p<0.03) without significant changes in MBP and HR (92.8+/-4.7 vs 92.4+/-3.2 mmHg, 63.1+/-2.1 vs 67.0+/-2.9 bpm). LVEF significantly raised at 15 min, peaked at 30 min and lasted up to 60 min after HEX. These findings suggest that in man, the acute administration of Hexarelin exerts a short-lasting, positive inotropic effect. This effect seems GH-independent and might be mediated by specific GHS myocardial receptors. (J. Endocrinol. Invest. 22: 266-272, 1999) (C)1999, Editrice Kurtis