Document Detail

SB 203580, an inhibitor of p38 MAPK, abolishes infarct-limiting effect of ischemic preconditioning in isolated rabbit hearts.
MedLine Citation:
PMID:  11192367     Owner:  NLM     Status:  MEDLINE    
There is debate concerning the involvement of p38 mitogen-activated protein kinase (MAPK) in ischemic preconditioning (PC). At the center of the controversy are data obtained after administration of SB 203580, a specific inhibitor of p38 MAPK. Whereas several studies have reported that SB 203580 abolishes the cardioprotective effect of PC, others claim that this compound is actually cardioprotective against ischemia. Many of these latter observations have been made in isolated myocardial cells. Accordingly the present study was designed to test the effect of SB 203580 in a model of preconditioning in intact rabbit hearts in which infarct size was the end-point. Isolated hearts experienced 30 min of regional ischemia followed by 120 min of reperfusion. Infarct size was measured with triphenyltetrazolium chloride. In control hearts infarction was 30.2 +/- 3.3% of the risk zone. PC with 5 min of global ischemia and 10 min of reperfusion before the 30-min period of ischemia significantly reduced infarct size to 10.2 +/- 2.4% (P < 0.05 vs. control). SB 203580 (2 microM) added to the perfusate for 20 min starting 5 min before the index ischemia totally blocked the protection from PC (27.4 +/- 3.3% infarction). SB 203580 alone had no effect on infarct size (28.6 +/- 4.6% infarction). These results reveal that SB 203580 does not affect infarct size on its own, but selectively blocks preconditioning's anti-infarct effect in the intact rabbit heart.
A Nakano; M V Cohen; S Critz; J M Downey
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Basic research in cardiology     Volume:  95     ISSN:  0300-8428     ISO Abbreviation:  Basic Res. Cardiol.     Publication Date:  2000 Dec 
Date Detail:
Created Date:  2001-01-15     Completed Date:  2001-03-08     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0360342     Medline TA:  Basic Res Cardiol     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  466-71     Citation Subset:  IM    
Department of Physiology, University of South Alabama, College of Medicine, Mobile 36688, USA.
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MeSH Terms
Coronary Circulation / drug effects
Enzyme Inhibitors / pharmacology*
Heart / drug effects*
Imidazoles / pharmacology*
Ischemic Preconditioning, Myocardial*
Mitogen-Activated Protein Kinases / antagonists & inhibitors*
Myocardial Infarction / pathology*,  physiopathology
Myocardium / pathology
Pyridines / pharmacology*
Ventricular Function, Left / drug effects
p38 Mitogen-Activated Protein Kinases
Grant Support
Reg. No./Substance:
0/Enzyme Inhibitors; 0/Imidazoles; 0/Pyridines; 0/SB 203580; EC Protein Kinases; EC Mitogen-Activated Protein Kinases

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