Area of risk was similar among all treatment groups. Myocardial infarction area was increased between 2 and 24 hours after reperfusion in all intervention groups. PostC significantly reduced myocardial infarction size after reperfusion. Treatment with AG490 and wortmannin alone had no effect on myocardial infarc tion after reperfusion in I/R group. Myocardial Vandetanib 443913-73-3 apoptosis after prolonged reperfusion There were no TUNEL positive cells in the sham group. There was more apoptosis at 24 h compared to 2 h reperfusion in all intervention groups. PostC significantly reduced myocardial apoptosis at 2 and 24 h after reperfusion. Treating rats with AG490 or wort mannin significantly attenuated anti apoptosis effects of PostC. However, AG490 or wortmannin alone had no effect on apoptosis index after reperfusion in I/R group.

Myocardial Bcl 2 levels Both protein and mRNA levels of Bcl 2 were similar at 2 and 24 h Inhibitors,Modulators,Libraries in the control group. PostC elevated levels of Bcl 2 after reperfusion, which increased between 2 and 24 h after reperfusion. The JAK2 inhibitor AG490 decreased Bcl 2 levels after reperfusion. The PI3K inhi bitor wortmannin had no effects on Bcl 2 levels. Correlation between JAK2 STAT3 and PI3K/Akt signaling pathways in PostC PostC significant increased the expression of p STAT3 and p Akt. Administration of AG490 before PostC reduced p STAT3 and p Akt levels and attenuated the cardioprotection effect of PostC. Wortmannin also reduced p Akt levels and attenuated the cardioprotec tion effect of PostC but had no effect on p STAT3 levels.

Discussion The present study demonstrated that apoptosis follow ing I/R injury increases after prolonged reperfusion. The prolonged Inhibitors,Modulators,Libraries anti apoptotic effect of PostC may be related to elevation of Bcl 2 24 h after reperfusion which is regulated by the JAK2 STAT3 pathway. PI3K/Akt path way, regulated by JAK2 signaling, may be necessary in the protection of PostC. Previous studies have shown that oxidative stress, Ca2 overload, pH paradox and inflammation during early reperfusion are the major mediators of lethal injury which indicates that this period is important in the pathogenesis of reperfusion Inhibitors,Modulators,Libraries injury. Zhao et al. recently found that infarction size increases significantly between Inhibitors,Modulators,Libraries 6 h and 24 h after reperfusion in a canine model. In agreement with this, the present study also found that myocardial apoptosis increases after pro longed reperfusion in rat hearts.

Myocardial reperfusion injury may increase with the duration of reperfusion. However, Argaud et al. found that myocardial infarction size had no difference between 4 h and 72 h after reper fusion in rabbit hearts. The difference in animal species and the procedures Inhibitors,Modulators,Libraries to induce ischemia/reperfusion injury are considered to selleck Sorafenib be the reasons for these differ ent results. PostC was first described by Johansens group in 2003.