To determine whether IGF-1 opposes the stimulation of myocyte death in the 
surviving myocardium after infarction, transgenic mice overexpressing human 
IGF-1B in myocytes (FVB.Igf+/-) and wild-type littermates at 1.5 and 2.5 mo of 
age were subjected to coronary ligation and killed 7 d later. Myocardial 
infarction involved an average 50% of the left ventricle, and produced cardiac 
failure. In the region proximate to infarction, myocyte apoptosis increased 4. 
2-fold and 2.1-fold in nontransgenics at 1.5 and 2.5 mo, respectively. 
Corresponding increases in myocyte necrosis were 1. 8-fold and 1.6-fold. In 
contrast, apoptotic and necrotic myocyte death did not increase in FVB.Igf+/- 
mice at either age after infarction. In 2.5-mo-old infarcted nontransgenics, 
functional impairment was associated with a 29% decrease in wall thickness, 43% 
increase in chamber diameter, and a 131% expansion in chamber volume. 
Conversely, the changes in wall thickness, chamber diameter, and cavitary volume 
were 41, 58, and 48% smaller in infarcted FVB.Igf+/- than in nontransgenics. The 
differential response to infarction of FVB.Igf+/- mice resulted in an attenuated 
increase in diastolic wall stress, cardiac weight, and left and right 
ventricular weight-to-body wt ratios. In conclusion, constitutive overexpression 
of IGF-1 prevented activation of cell death in the viable myocardium after 
infarction, limiting ventricular dilation, myocardial loading, and cardiac 
hypertrophy.