Document Detail


Reduction of infarct size by gentle reperfusion without activation of reperfusion injury salvage kinases in pigs.
MedLine Citation:
PMID:  19656779     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
AIMS: 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).
METHODS AND 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).
CONCLUSION: Gentle reperfusion reduces infarct size in pigs, but RISK activation is not causally involved in this infarct size reduction.
Authors:
Judith Musiolik; Patrick van Caster; Andreas Skyschally; Kerstin Boengler; Petra Gres; Rainer Schulz; Gerd Heusch
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cardiovascular research     Volume:  85     ISSN:  1755-3245     ISO Abbreviation:  Cardiovasc. Res.     Publication Date:  2010 Jan 
Date Detail:
Created Date:  2009-12-16     Completed Date:  2010-02-19     Revised Date:  2011-11-02    
Medline Journal Info:
Nlm Unique ID:  0077427     Medline TA:  Cardiovasc Res     Country:  England    
Other Details:
Languages:  eng     Pagination:  110-7     Citation Subset:  IM    
Affiliation:
Institut für Pathophysiologie, Westdeutsches Herzzentrum Essen, Universitätsklinikum Essen, Hufelandstrasse 55, 45122 Essen, Germany.
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MeSH Terms
Descriptor/Qualifier:
Animals
Enzyme Activation
Extracellular Signal-Regulated MAP Kinases / physiology*
Glycogen Synthase Kinase 3 / physiology*
Myocardial Infarction / prevention & control*
Myocardial Reperfusion Injury / enzymology*
Phosphatidylinositol 3-Kinases / physiology*
Phosphorylation
Proto-Oncogene Proteins c-akt / physiology*
Ribosomal Protein S6 Kinases, 70-kDa / physiology*
Swine
Chemical
Reg. No./Substance:
EC 2.7.1.-/Phosphatidylinositol 3-Kinases; EC 2.7.11.1/Proto-Oncogene Proteins c-akt; EC 2.7.11.1/Ribosomal Protein S6 Kinases, 70-kDa; EC 2.7.11.1/glycogen synthase kinase 3 beta; EC 2.7.11.24/Extracellular Signal-Regulated MAP Kinases; EC 2.7.11.26/Glycogen Synthase Kinase 3

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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