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Ischemic Postconditioning (IPostC) Protects the Heart against in vivo Ischemia/Reperfusion (I/R) Injury with Effective Akt and ERK1/2 Activation and Decreased Superoxide Generation
Author(s) -
Zweier Jay,
Yang Fuchun,
Yang Changjun,
Varadharaj Saradhadevi,
Talukder M.A. Hassan
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1097.5
Subject(s) - cardioprotection , protein kinase b , medicine , ischemia , myocardial infarction , reperfusion injury , reactive oxygen species , ischemic preconditioning , pharmacology , apoptosis , cardiology , chemistry , biochemistry
Ischemic preconditioning confers robust cardioprotection against I/R injury; however, it is difficult to clinically translate because the onset of acute myocardial infarction (AMI) is unpredictable. There is now growing interest in IPostC, which is defined as brief intermittent cycles of ischemia (I) alternating with reperfusion (R) applied at the beginning of reflow. IPostC have been reported in several species; however, debate exists as to the magnitude of protection and optimal procedure of I and R cycles. Therefore, we investigated different protocols of IPostC for their cardioprotective efficacies. Rats were subjected to in vivo 30‐min I followed by different IPostC protocols (3 cycles of 10‐sec R/I; 6 cycles of 10‐sec R/I; 3 cycles of 20‐sec R/I; or 3 cycles of 30‐sec R/I) and then 24‐hr R. MI was evaluated 24‐hr after R and the most effective IPostC protocol was investigated for cardioprotective mechanisms. Signaling pathways were characterized for prosurvival kinase (Akt and ERK1/2) activation and reactive oxygen species (ROS) generation. The major findings are that all protocols of IPostC reduced MI but 6 cycles of 10‐sec IPostC was most effective, and it was associated with activation of Akt and ERK1/2, and reduced myocardial ROS. Thus, multiple short‐cycles of IPostC is highly effective in myocardial salvage in the setting of AMI, and it may represent a novel translatable approach in cardioprotection.