Abstract 14248: Infarct Size Reduction by Remote Ischemic Perconditioning in Pigs Requires Activation of Stat3 but Not Akt and Erk
Brief episodes of ischemia/reperfusion (I/R) in a tissue or organ remote from the heart reduce infarct size after sustained severe myocardial I/R in all species tested so far, including humans. Remote ischemic conditioning can be induced before (pre) or during (per) myocardial ischemia. In pigs, cardioprotection by remote ischemic preconditioning requires the activation of the signal transducer and activator of transcription 3 (STAT3), whereas the activation protein kinase B (Akt) and extracellular regulated kinases (ERK) is not causal for cardioprotection (Circ Res 2015;117:279-88). We now identified the myocardial signal transduction of remote ischemic perconditioning (RPERC).
Anesthetized open-chest pigs were subjected to 60 min occlusion of the left anterior descending coronary artery (LAD) and 180 min reperfusion (PLA; n=10). RPERC (n=10) was induced by 4х5/5 min hindlimb I/R during the last 40 min of LAD occlusion. Infarct size (TTC) was calculated as % of area at risk (AAR). Myocardial biopsies were taken at baseline and at 10 min reperfusion from the AAR. The phosphorylation (phospho) of Akt, ERK and STAT3 was determined by Western blot. RPERC was also performed in the presence of either Akt+ERK-blockade (Wortmannin/U0126; n=4) or STAT3-blockade (AG490; n=4).
RPERC reduced infarct size and increased the phosphorylation of STAT3 at 10 min reperfusion vs. PLA. STAT3-blockade abolished STAT3 phosphorylation and infarct size reduction, whereas Akt+ERK-blockade abolished Akt and ERK activation, but not infarct size reduction (see Table).
In pigs, STAT3 activation is required for cardioprotection by RPERC, whereas activation of Akt and ERK is not. Thus, in pigs cardioprotection by RPERC is characterized by the same signal transduction pattern as remote ischemic preconditioning and local ischemic postconditioning (Circ Res 2011;109:1302-8).
Author Disclosures: P. Kleinbongard: None. S. Gent: None. A. Skyschally: None. G. Heusch: None.
- © 2016 by American Heart Association, Inc.