title: Ischemic postconditioning in pigs: no causal role for RISK activation.
abstract: Ischemic postconditioning (IPoC) reduces infarct size following ischemia/reperfusion. Whether or not phosphorylation of RISK (reperfusion injury salvage kinases) (AKT, ERK1/2, P70S6K, GSK3beta) 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).
authors.affiliation: Institut für Pathophysiologie, Universitätsklinikum Essen, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Skyschally
authors.forename: Patrick
authors.initials: P
authors.lastname: van Caster
authors.forename: Kerstin
authors.initials: K
authors.lastname: Boengler
authors.forename: Petra
authors.initials: P
authors.lastname: Gres
authors.forename: Judith
authors.initials: J
authors.lastname: Musiolik
authors.forename: Dustin
authors.initials: D
authors.lastname: Schilawa
authors.forename: Rainer
authors.initials: R
authors.lastname: Schulz
authors.forename: Gerd
authors.initials: G
authors.lastname: Heusch
mesh_terms: D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D002070:Butadienes / Q000494:pharmacology; D054059:Coronary Occlusion / Q000201:enzymology / Q000473:pathology; D004789:Enzyme Activation / Q000187:drug effects; D004790:Enzyme Induction; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology*; D000071679:Glycogen Synthase Kinase 3 beta; D048369:MAP Kinase Kinase 1 / Q000037:antagonists & inhibitors / Q000502:physiology; D048370:MAP Kinase Kinase 2 / Q000037:antagonists & inhibitors / Q000502:physiology; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology*; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology*; D009203:Myocardial Infarction / Q000201:enzymology / Q000473:pathology; D015425:Myocardial Reperfusion; D015428:Myocardial Reperfusion Injury / Q000201:enzymology* / Q000517:prevention & control; D009570:Nitriles / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology*; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology*; D013552:Swine; D013556:Swine, Miniature; D000077191:Wortmannin
chemical_list: D000730:Androstadienes; D002070:Butadienes; D009570:Nitriles; D047428:Protein Kinase Inhibitors; C113580:U 0126; D019869:Phosphatidylinositol 3-Kinases; D000071679:Glycogen Synthase Kinase 3 beta; D051057:Proto-Oncogene Proteins c-akt; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D038362:Glycogen Synthase Kinase 3; D048369:MAP Kinase Kinase 1; D048370:MAP Kinase Kinase 2; D000077191:Wortmannin