Growth hormone therapy in ischemic heart disease
Although the heart has not been a traditional target of growth hormone (GH), a consistent body of evidence now supports its importance in governing cardiac structure and function, and its possible utility in treating ischemic heart disease. In studies of normal rats, we and others have shown that exogenous GH administration produces concentric hypertrophy, reduced systemic vascular resistance and augmented systolic function, at least in part due to altered calcium handling. This constellation of actions is ideally suited to modulate the effects of large myocardial infarction and subsequent heart failure. Indeed, our studies have shown that GH attenuates left ventricular remodeling and improves cardiac function following large myocardial infarction in the rat (infarct size ∼40% of left ventricular myocardium). In GH-treated animals, left ventricular dilatation was reduced, and the non-infarcted myocardium showed hypertrophy without fibrosis. Functional improvements included: increased stroke volume, cardiac output and fractional shortening, as well as prevention of the development of diastolic filling abnormalities. Absence of an increase in myocardial insulin-like growth factor (IGF)-1 mRNA suggests that these effects were not accompanied by an increase in the local expression of IGF-1, GH's tissue mediator. Further, and perhaps most impor-tantly, these positive effects were of far greater magnitude than those seen in the same rat model of myocardial infarction with the angiotensin-converting enzyme inhibitor, captopril. In GH-deficient animals, postinfarction remodeling and dysfunction are more marked than in normal rats, suggesting that GH is necessary for a normal response to the injury of myocardial infarction. Others have shown similar benefits in more chronic models of ischemic heart failure. The mechanisms by which GH yields benefits in ischemic heart failure are many: the ability of GH to cause hypertrophy of non-infarcted myocardium and to reduce peripheral vascular resistance combine to have the positive effect of lowering afterload, which directly augments cardiac performance and also reduces cavity dilatation. Enhancement of myofilament calcium responsiveness is a second direct effect promoting improved contractility. In addition, preservation of the collagen matrix limits aneurysm formation. These animal data strongly support the hypothesis that GH administration may be beneficial to patients with myocardial infarction. Further research is needed to clarify more fundamental mechanisms of action and to define this potential clinical use more clearly. ©1998, Editrice Kurtis.
Cittadini, A; Douglas, PS
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