title: Later phase cardioprotection of ischemic post-conditioning against ischemia/reperfusion injury depends on iNOS and PI3K-Akt pathway.
abstract: BACKGROUND
  The cardioprotection of ischemic post-conditioning (IPO) has been well demonstrated after a short period of reperfusion. However, little is known about the long-term effects of IPO. This study aimed to investigate the long term cardioprotection of IPO in a rat myocardial ischemia/reperfusion model and to explore the potential mechanism.
  
  
  RESULTS
  Rats were either sham-operated (Sham group) or underwent 30-min left anterior descending coronary artery ischemia followed by immediate reperfusion (I/R group) or post-conditioning with 5 cycles of 10-s ischemia and 10-s reperfusion (IPO group). At 24 h after reperfusion, infarct size reduced from 34.7±1.1% in I/R group to 24.9±1.3% in IPO group (P<0.05) and the iNOS expression in IPO group was 4.7-fold higher than in I/R group. iNOS inhibitor 1400 W (1 mg/kg, 5 min before postconditioning or reperfusion) prevented the increase in iNOS expression and abolished IPO-induced protection (34.4±1.0%, P>0.05 vs. I/R group). When rats were treated with PI3K inhibitor LY294002 5 min before reperfusion (0.3 mg/kg), p-Akt expression at R 3 h and iNOS expression at R 24 h were significantly inhibited. Moreover, the delayed infarct-sparing effect of IPO was absent in the presence of LY294002.
  
  
  CONCLUSIONS
  IPO has prolonged cardioprotective effects and iNOS as an important downstream effector of PI3K-Akt pathway contributes to the delayed phase cardioprotection of IPO.
authors.affiliation: Department of Anesthesiology, Shandong Provincial Hospital Affiliated to Shandong University Jinan 250021, China.
authors.forename: Gongming
authors.initials: G
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, Shandong Provincial Hospital Affiliated to Shandong University Jinan 250021, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Nephrology, Taian Central Hospital Taian 271000, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, Shandong Provincial Hospital Affiliated to Shandong University Jinan 250021, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, Shandong Provincial Hospital Affiliated to Shandong University Jinan 250021, China.
authors.forename: Ligong
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, Shandong Provincial Hospital Affiliated to Shandong University Jinan 250021, China.
authors.forename: Le
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, Shandong Provincial Hospital Affiliated to Shandong University Jinan 250021, China.
authors.forename: Bei
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Anesthesiology, Shandong Provincial Hospital Affiliated to Shandong University Jinan 250021, China.
authors.forename: Mengyuan
authors.initials: M
authors.lastname: Zhang
keywords: Akt; Delayed cardioprotection; inducible nitric oxide synthase; ischemia-reperfusion injury; ischemic post-conditioning; phosphatidylinositol 3-kinase