Ischemic preconditioning (IPC), i.e. brief episodes of non-lethal myocardial ischemia/reperfusion (IR) prior to sustained ischemia with subsequent reperfusion, reduces infarct size in all tested species so far, including humans. In rodents, the cardioprotective signal transduction causally involves an activation of AKT, ERK1/2 and STAT3. However, there are apparent species differences in the signal transduction between rodents and larger mammals such as pigs, where data on IPC's signal transduction are inconsistent for AKT and ERK1/2. The role of STAT3 has not yet been analyzed. Pigs were subjected to 60 min LAD coronary artery occlusion and 180 min reperfusion without or with IPC (two cycles of 3 min occlusion separated by 2 min of reperfusion 15 min prior to sustained IR). Infarct size was analyzed by TTC-staining, and AKT, ERK1/2 and STAT3 phosphorylation was quantified in myocardial biopsies taken at baseline and early reperfusion. AG490 was used to block the STAT3 signaling pathway. IPC reduced infarct size (% area at risk; mean±SEM: IR: 45±3 vs. IPC: 18±3, p<0.05). AKT and ERK1/2 phosphorylation was increased at early reperfusion without and with IPC. In contrast, STAT3 phosphorylation at early reperfusion was only increased with IPC (% of baseline; mean±SEM: IR: 126±29 vs. IPC: 408±147, p<0.05). AG490 prevented the IPC-related increase of STAT3 phosphorylation at reperfusion (% of baseline; mean±SEM: 82±12) and abolished IPC's cardioprotection (% area at risk; mean±SEM: 35±4). In pigs, increased phosphorylation of STAT3 is causally involved, whereas AKT and ERK1/2 seem to play no role in IPC's cardioprotection.
- Ischemic preconditioning
- Copyright © 2016, American Journal of Physiology-Heart and Circulatory Physiology