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(Circulation Research. 2009;104:15.)
© 2009 American Heart Association, Inc.

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Ischemic Postconditioning in Pigs

No Causal Role for RISK Activation

Andreas Skyschally^*, Patrick van Caster^*, Kerstin Boengler, Petra Gres, Judith Musiolik, Dustin Schilawa, Rainer Schulz, Gerd Heusch

From the Institut für Pathophysiologie, Universitätsklinikum Essen, Germany.

Correspondence to Prof Dr Gerd Heusch, FRCP, Institut für Pathophysiologie, Universitätsklinikum Essen, Hufelandstrasse 55, 45122 Essen, Germany. E-mail gerd.heusch{at}uk-essen.de

Ischemic postconditioning (IPoC) reduces infarct size following ischemia/reperfusion. Whether or not phosphorylation of RISK (reperfusion injury salvage kinases) (AKT, ERK1/2, P70S6K, GSK3β) is causal for protection by IPoC is controversial. We therefore studied the impact of RISK on IPoC in anesthetized pigs subjected to 90 minutes of left anterior descending coronary artery hypoperfusion and 120 minutes of reperfusion. In protocol 1, IPoC, by 6 cycles of 20/20 seconds of reperfusion/reocclusion (n=13), was compared with immediate full reperfusion (IFR) (n=15). In protocol 2, IPoC (n=4) or IFR (n=4) was performed with pharmacological RISK blockade by IC coinfusion of Wortmannin and U0126. Infarct size was determined by TTC staining, and the expression of phosphorylated RISK proteins by Western blot analysis in biopsies. In protocol 1, infarct size was 20±3% (percentage of area at risk; mean±SEM) with IPoC and 33±4% (P<0.05) with IFR. RISK phosphorylation increased with reperfusion but was not different between IPoC and IFR. In protocol 2, Wortmannin and U0126 blocked the increases in RISK phosphorylation during reperfusion, but infarct size was still smaller with IPoC (15±7%) than with IFR (35±6%; P<0.05).

Key Words: cardioprotection • infarct size • reperfusion injury

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