Exogenous growth hormone: a new therapy for dilated cardiomyopathy
ABSTRACT Heart failure is an epidemic within the United States and, despite current medical therapy, carries a high mortality rate. Growth hormone and insulin-like growth factor-1 have known direct effects on the cardiovascular system. Improvement in contractility, reduction in wall stress, and increase in cardiac performance have been noted in animal experiments. Furthermore, preliminary data from human trials are encouraging. This report outlines the biology of growth hormone, the experimental and human data to support clinical trials of growth hormone treatment, and the outcome of trials reported to date.
- SourceAvailable from: Matthias G. Friedrich[show abstract] [hide abstract]
ABSTRACT: Some studies have suggested that treatment with recombinant human growth hormone (rhGH) increases left-ventricular mass and improves haemodynamic and functional status in patients with heart failure due to dilated cardiomyopathy. We did a double-blind, randomised, placebo-controlled study of rhGH in patients with chronic heart failure due to dilated cardiomyopathy. 50 patients (43 men) were randomly allocated treatment with subcutaneous rhGH (2 IU daily) or placebo for a minimum of 12 weeks. The primary endpoints were the effects on left-ventricular mass and systolic wall stress. The secondary endpoints were the effects on left-ventricular size and function. Data were analysed by intention to treat. Patients in the rhGH group had an increase in left-ventricular mass compared with those in the placebo group (27%, p=0.0001). There was no significant difference in left-ventricular systolic wall stress, mean blood pressure, or systemic vascular resistance between the two groups. New York Heart Association functional class, left-ventricular ejection fraction, and distance on the 6 min walking test were unchanged. The change in serum insulin-like growth factor (IGF)-I concentrations (rhGH 77 ng/mL; placebo -19 ng/mL, GH vs placebo p=0.0001) was significantly related to the change in left-ventricular mass (r=0.55, p=0.0001). One patient in the rhGH group was withdrawn at 6 weeks because of worsening heart failure. There is a significant increase in left-ventricular mass in patients with dilated cardiomyopathy given rhGH but this is not accompanied by an improvement in clinical status. Changes in left-ventricular mass are related to changes in serum IGF-I concentrations. Whether a longer treatment period would provide clinical benefits and decrease mortality is unknown.The Lancet 05/1998; 351(9111):1233-7. · 39.06 Impact Factor
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ABSTRACT: In the newborn several situations of hyperinsulinism can be associated with myocardial hypertrophy and increased contractility. Insulin and the insulin-like growth factors (IGF) are derived from a common ancestral molecule. Insulin exerts mainly metabolic action, whereas the IGFs promote cell multiplication and differentiation. Using an assay system of cultured neonatal myocardial cells the stimulatory action of insulin and the insulin-like growth factors I and II on myocardial cell contractility was investigated. Spontaneously beating aggregates of myocardial cells were synchronized by an electric impulse generator. Contractility was measured via the amplitude of contraction by an optoelectronic system. Insulin at a concentration of 6,250 and 12,500 microU/ml increased the contractility by 11 and 18%; IGF-I at a concentration of 12 and 25 ng/ml, and IGF-II at a concentration of 25 and 50 ng/ml increased the contractility by 16 and 22%, and 13 and 18%, respectively. Lower concentrations did not provoke a significant increase in contractility. Insulin only in supraphysiological doses increases the contractility of neonatal myocardial rat cells, whereas both insulin-like growth factors act in physiological concentrations. Therefore, during hyperinsulinism insulin may increase myocardial contractility via the IGF receptor and not via the insulin receptor.Archiv für Kreislaufforschung 01/1988; 83(6):647-54. · 5.90 Impact Factor
- The Lancet 05/1997; 349(9058):1067-8. · 39.06 Impact Factor