Intrapericardial IGF-I improves cardiac function in an ovine model of chronic heart failure.
BACKGROUND
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.


METHODS
Intrapericardial IGF-I (15 microg/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.


RESULTS
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.


CONCLUSIONS
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.
Matthews
Kenneth G
KG
Functional Muscle Genomics Group, AgResearch Ruakura, East Street, Hamilton, New Zealand. ken.matthews@agresearch.co.nz
Devlin
Gerard P
GP
Stuart
Selwyn P
SP
Jensen
Juliet A
JA
Doughty
Robert N
RN
Conaglen
John V
JV
Bass
James J
JJ
D000279:Administration, Cutaneous; D000818:Animals; D006328:Cardiac Catheterization; D004195:Disease Models, Animal; D005260:Female; D006333:Heart Failure / Q000188:drug therapy*; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage*; D009206:Myocardium / Q000378:metabolism; D010496:Pericardium; D011897:Random Allocation; D012756:Sheep; D013318:Stroke Volume / Q000187:drug effects; D016277:Ventricular Function, Left / Q000187:drug effects*
D007334:Insulin-Like Growth Factor I