M. Buerke et al., CARDIOPROTECTIVE EFFECT OF INSULIN-LIKE GROWTH-FACTOR-I IN MYOCARDIAL-ISCHEMIA FOLLOWED BY REPERFUSION, Proceedings of the National Academy of Sciences of the United Statesof America, 92(17), 1995, pp. 8031-8035
In the present study, the cardioprotective effects of insulin-like gro
wth factor I (IGF-I) were examined in a murine model of myocardial isc
hemia reperfusion (i.e., 20 min + 24 hr), IGF-I (1-10 mu g per rat) ad
ministered 1 hr prior to ischemia significantly attenuated myocardial
injury (i.e., creatine kinase loss) compared to vehicle (P < 0.001), I
n addition, cardiac myeloperoxidase activity, an index of neutrophil a
ccumulation, in the ischemic area was significantly attenuated by IGF-
I (P < 0.001), This protective effect of IGP-I was not observed with d
es-(1-3)-IGF-I. Immunohistochemical analysis of ischemic-reperfused my
ocardial tissue demonstrated markedly increased DNA fragmentation due
to programmed cell death (i.e., apoptosis) compared to nonischemic myo
cardium. Furthermore, IGF-I significantly attenuated the incidence of
myocyte apoptosis after myocardial ischemia and reperfusion, Therefore
, IGF-I appears to be an effective agent for preserving ischemic myoca
rdium from reperfusion injury and protects via two different mechanism
s-inhibition of polymorphonuclear leukocyte-induced cardiac necrosis a
nd inhibition of reperfusion-induced apoptosis of cardiac myocytes.