Intrapericardial IGF-I Improves Cardiac Function in an Ovine Model of Chronic Heart Failure

Following myocardial infarction, progressive deterioration of left ventricular function often follows, leading eventually to overt heart failure. In the myocardium, there is increased expression of insulin-like growth factor I (IGF-I) mRNA, protein and receptor levels, particularly in the peri-infar...

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Bibliographic Details
Published in:Heart, lung & circulation lung & circulation, 2005-06, Vol.14 (2), p.98-103
Main Authors: Matthews, Kenneth G., Devlin, Gerard P., Stuart, Selwyn P., Jensen, Juliet A., Doughty, Robert N., Conaglen, John V., Bass, James J.
Format: Article
Language:English
Subjects:
Administration, Cutaneous
Animals
Cardiac
Cardiac Catheterization
Disease Models, Animal
Female
Heart
Heart Failure - drug therapy
Insulin-Like Growth Factor I - administration & dosage
Myocardial infarction
Myocardium
Myocardium - metabolism
Pericardium
Random Allocation
Sheep
Stroke Volume - drug effects
Ventricular Function, Left - drug effects
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Summary:Following myocardial infarction, progressive deterioration of left ventricular function often follows, leading eventually to overt heart failure. In the myocardium, there is increased expression of insulin-like growth factor I (IGF-I) mRNA, protein and receptor levels, particularly in the peri-infarct zone, suggesting that IGF-I has a role to play in post-infarct cardiac structure and function. In this study, we examine the effects of exogenous IGF-I on cardiac function. Intrapericardial IGF-I (150 μg/kg/d, n = 3) or vehicle (sterile saline, n = 3) was administered to sheep in chronic heart failure and the results of intrapericardial delivery compared with those of subcutaneous delivery. Left ventricular ejection fraction (EF) was measured to assess cardiac performance. Concentrations of plasma IGF-I were quantified by radioimmunoassay. Intrapericardial delivery of IGF-I resulted in a rapid and sustained increase ( P < 0.001) in EF, which remained elevated 14 days after cessation of treatment. Subcutaneous IGF-I treatment did not affect EF. Both subcutaneous and intrapericardial IGF-I administration increased concentrations of plasma IGF-I, although concentrations declined prior to the cessation of treatment. We conclude that the higher concentration of IGF-I in the myocardium, which results from intrapericardial delivery significantly increases EF in chronic heart failure but that subcutaneous delivery of IGF-I does not.
ISSN:1443-9506
1444-2892
DOI:10.1016/j.hlc.2005.02.002