[Ischemic postconditioning attenuates ischemia/reperfusion injury in isolated hypertrophied rat heart].
OBJECTIVE
To explore the effects of ischemic postconditioning on ischemia/reperfusion injury in isolated hypertrophied rat heart and investigate the signal transduction pathway changes induced by ischemia postconditioning.


METHODS
Cardiac hypertrophy was induced in rats by abdominal aortic banding, and isolated hypertrophied rat heart ischemia/reperfusion model was made by Langendorff technique to evaluate the effects of ischemia postconditioning on left ventricular systole pressure, coronary artery flow, creatine phosphokinase (CPK) and lactate dehydrogenase (LDH) release, myocardial infarction size, and the level of myocardial phospho-protein kinase B/Akt (Ser473), phospho-glycogen synthase kinase-3beta (Ser9). Following groups were studied (n = 12 each group): IR, 30 min ischemia (I)/60 min Reperfusion (R); Post: 30 min ischemia, 6 circles of 10 s I/10 s R followed by 60 min R; Post Wort: 30 min ischemia, 6 circles of 10 s I/10 s R, wortmannin (10(-7) mol/L) followed by 60 min R; Wort: 30 min ischemia, wortmannin (10(-7) mol/L) followed by 60 min R.


RESULTS
Left ventricular systolic pressure and coronary artery flow were significantly increased, myocardial infarction size and the release of CPK, LDH significantly reduced in Post group compared to that in IR group. Phospho-protein kinase B/Akt (Ser473) and phospho-glycogen synthase kinase-3beta (Ser9) levels were also significantly higher in Post group than that in IR group. Phosphatidylinositol 3-kinase (PI3K) inhibitor wortmannin prevented the increase of phospho-protein kinase B/Akt (Ser473) and phospho-glycogen synthase kinase-3beta (Ser9) induced by ischemic postconditioning, but only partly abolished the cardioprotection of ischemic postconditioning.


CONCLUSIONS
Ischemic postconditioning attenuates ischemia/reperfusion injury in isolated hypertrophied rat heart. The cardioprotective effects of ischemic postconditioning were partly mediated through PI3K/Akt/GSK-3beta signaling pathway.
Peng
Long-yun
LY
Cardiovascular Research Institute of Sun Yat-sen University, Department of Cardiovascular Medicine, First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China.
Ma
Hong
H
He
Jian-gui
JG
Gao
Xiu-ren
XR
Zhang
Yan
Y
He
Xiao-hong
XH
Zhai
Yuan-sheng
YS
Zhang
Xue-jiao
XJ
D000818:Animals; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000628:therapy*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction
D019869:Phosphatidylinositol 3-Kinases; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3