title: Reduction of infarct size by gentle reperfusion without activation of reperfusion injury salvage kinases in pigs.
abstract: OBJECTIVE
  Reperfusion is mandatory to salvage ischaemic myocardium from infarction, but also induces additional reperfusion injury and contributes to infarct size (IS). Gentle reperfusion (GR) has been proposed to attenuate reperfusion injury, but this remains contentious. We now investigated whether (i) GR reduces IS and (ii) GR is associated with the activation of reperfusion injury salvage kinases (RISK).
  
  
  RESULTS
  Anaesthetized pigs were subjected to 90 min left anterior descending coronary artery hypoperfusion and 120 min reperfusion. GR was induced by slowly increasing coronary inflow back to baseline over 30 min, using an exponential algorithm [F(t) = F(i)+e(-(0.1)(t)((min)-3)).(F(b)-F(i)); F(b), coronary inflow at baseline; F(i), coronary inflow during ischaemia; n = 12]. Pigs subjected to immediate full reperfusion (IFR; n = 13) served as controls. IS was determined by triphenyl tetrazolium chloride staining. The expression level of phosphorylated RISK proteins was determined by western blot analysis in myocardial biopsies taken at baseline, after 80-85 min ischaemia and at 10, 30, and 120 min reperfusion. In additional experiments with IFR (n = 3) and GR (n = 3), the PI3-AKT and MEK1/2-ERK1/2 pathways were pharmacologically blocked (BL). IS was 37 +/- 2% (mean +/- SEM) of the area at risk with IFR and 29 +/- 1% (P < 0.05) with GR. RISK phosphorylation was similar between GR and IFR at baseline and 85 min ischaemia. At 10 min reperfusion, RISK phosphorylation was increased with IFR, but not with GR. At 30 and 120 min reperfusion, RISK phosphorylation was still greater with IFR than GR. RISK blockade did not abolish the IS reduction by GR (BL-IFR: 27 +/- 4% of the area at risk; BL-GR: 42 +/- 5%; P < 0.05).
  
  
  CONCLUSIONS
  Gentle reperfusion reduces infarct size in pigs, but RISK activation is not causally involved in this infarct size reduction.
authors: Institut für Pathophysiologie, Westdeutsches Herzzentrum Essen, Universitätsklinikum Essen, Hufelandstrasse 55, 45122 Essen, Germany.
authors: Judith
authors: J
authors: Musiolik
authors: Patrick
authors: P
authors: van Caster
authors: Andreas
authors: A
authors: Skyschally
authors: Kerstin
authors: K
authors: Boengler
authors: Petra
authors: P
authors: Gres
authors: Rainer
authors: R
authors: Schulz
authors: Gerd
authors: G
authors: Heusch
mesh_terms: D000818:Animals; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology*; D038362:Glycogen Synthase Kinase 3 / Q000502:physiology*; D000071679:Glycogen Synthase Kinase 3 beta; D009203:Myocardial Infarction / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000201:enzymology*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology*; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000502:physiology*; D013552:Swine
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D000071679:Glycogen Synthase Kinase 3 beta; D051057:Proto-Oncogene Proteins c-akt; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D048049:Extracellular Signal-Regulated MAP Kinases; D038362:Glycogen Synthase Kinase 3