| dc.description.abstract | The growth hormone/insulin-like growth factor I (GH/IGF-I) system plays an important role for cardiac development, structure and function. Recently, data from experimental and clinical studies have suggested the use of GH as treatment after myocardial infarction (MI) affecting cardiac remodeling and development of heart failureThe aim of this thesis was to study the effects of GH on cardiac structure, function and energy metabolism in normal and failing heart.To evaluate the effect of GH treatment on left ventricular (LV) remodeling, we used different experimental models: a rat model of experimental MI, hypophysectomised (hx) rats and transgenic mice overexpressing bovine GH (bGH). Transthoracic echocardiography and 31P magnetic resonance spectroscopy, were used to evaluate geometry, systolic and diastolic function as well as energy metabolism of LV in vivo. Biochemical analysis including high pressure liquid chromatography and histological evaluation were also performed.Three days after MI, LV internal diameter increased significantly compared with control rats. Systolic and diastolic indexes of LV function were significantly deteriorated after MI. Three weeks later a further dilatation of LV and a more spherical shape were observed in MI rats. Phosphocreatine (PCr) to ATP ratio was significantly lower in MI rats three days and three weeks after MI. Short term (9 days) treatment with GH alone or in combination with metoprolol preserved the LV systolic function after MI, whereas three weeks treatment with GH after MI preserved systolic function and attenuated the remodeling. Plasma and myocardium tissue of catecholamines and brain natriuretic peptide levels were significantly decreased after GH treatment. Moreover, three weeks treatment with GH normalized PCr/ATP in MI rats.GH administration in hx rat increase body weight, heart weight, improved LV performance and myocardial energy metabolism. In transgenic bGH mice, hypertrophy of LV with poor systolic performance was observed. Moreover, a decrease in PCr/ATP ratios associated with qualitative changes on mitochondrial structure was detected in LV from bGH mice. GH plays an important role for the maintenance of normal cardiac structure, function and myocardial energy metabolism. Short term treatment with GH after MI attenuated the LV remodeling, preserved systolic function, improved myocardial bioenergetics and decreased neurohormonal activation. Long term exposures to high levels of GH leads to cardiac hypertrophy, poor performance and decreased energy reserve. | en |
