Cardioprotective effect of insulin-like growth factor I in myocardial ischemia followed by reperfusion.
In the present study, the cardioprotective effects of insulin-like growth factor I (IGF-I) were examined in a murine model of myocardial ischemia reperfusion (i.e., 20 min + 24 hr). IGF-I (1-10 micrograms per rat) administered 1 hr prior to ischemia significantly attenuated myocardial injury (i.e., creatine kinase loss) compared to vehicle (P < 0.001). In addition, cardiac myeloperoxidase activity, an index of neutrophil accumulation, in the ischemic area was significantly attenuated by IGF-I (P < 0.001). This protective effect of IGF-I was not observed with des-(1-3)-IGF-I. Immunohistochemical analysis of ischemic-reperfused myocardial tissue demonstrated markedly increased DNA fragmentation due to programmed cell death (i.e., apoptosis) compared to nonischemic myocardium. 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 myocardium from reperfusion injury and protects via two different mechanisms--inhibition of polymorphonuclear leukocyte-induced cardiac necrosis and inhibition of reperfusion-induced apoptosis of cardiac myocytes.
Buerke
M
M
Department of Physiology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Murohara
T
T
Skurk
C
C
Nuss
C
C
Tomaselli
K
K
Lefer
A M
AM
D000818:Animals; D015415:Biomarkers / Q000032:analysis; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D008297:Male; D017202:Myocardial Ischemia / Q000473:pathology / Q000503:physiopathology* / Q000517:prevention & control; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000201:enzymology / Q000473:pathology; D009504:Neutrophils / Q000201:enzymology / Q000502:physiology; D010446:Peptide Fragments / Q000494:pharmacology; D009195:Peroxidase / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley
D015415:Biomarkers; D002316:Cardiotonic Agents; D010446:Peptide Fragments; C058957:insulin-like growth factor 1, des-(1-3)-; D007334:Insulin-Like Growth Factor I; D009195:Peroxidase