Document Detail

Reduced susceptibility to ischemia-induced arrhythmias in the preconditioned rat heart is independent of PI3-kinase/Akt.
MedLine Citation:
PMID:  19627174     Owner:  NLM     Status:  MEDLINE    
We examined the involvement of phosphatidylinositol 3-kinase (PI3K) and its effector protein kinase B (Akt) in cardioprotective effects of ischemic preconditioning (PC) with particular regards to its role in the protection against ischemia-induced arrhythmias in isolated perfused rat heart. PI3K/Akt inhibitor wortmannin (100 nM) was administered 15 min prior to 30-min regional (left anterior descending coronary artery occlusion) ischemia for the study of ischemic arrhythmias in the hearts perfused at constant coronary flow or prior to 30-min global ischemia followed by 2-h reperfusion for the infarct size (IS) determination (tetrazolium staining) in the hearts perfused at constant pressure. PC procedure (one cycle of ischemia/reperfusion, 5 min each) significantly reduced the total number of ventricular premature complexes (PVC) and severity of arrhythmias (arrhythmia score; AS) over the whole period of left anterior descending coronary artery occlusion in comparison with non-PC controls (PVC 166+/-40; AS 1.6+/-0.2 vs. 550+/-60 and 3.2+/-0.2; respectively; P<0.05). In a setting of global ischemia/reperfusion, PC decreased IS (in % of the left ventricle, LV) by 73 %. Pretreatment with wortmannin modified neither arrhythmogenesis nor IS in the non-PC hearts. Bracketing of PC with wortmannin did not abolish antiarrhythmic protection (PVC 92+/-25; AS 1.7+/-0.2; P<0.05 vs. non-PC hearts). On the other hand, wortmannin increased IS/LV in the PC hearts to 24+/-1.2 % as compared with 9 +/- 0.6 % in the untreated ones (P<0.05). In conclusion, PI3K/Akt inhibition did not affect reduced arrhythmogenesis during ischemia in the PC hearts indicating that in contrast to its positive role in the irreversible myocardial injury, PI3K/Akt activity is not required for protection induced by PC against ischemic arrhythmias in the rat heart.
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Physiological research / Academia Scientiarum Bohemoslovaca     Volume:  58     ISSN:  0862-8408     ISO Abbreviation:  Physiol Res     Publication Date:  2009  
Date Detail:
Created Date:  2009-07-24     Completed Date:  2009-09-02     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  9112413     Medline TA:  Physiol Res     Country:  Czech Republic    
Other Details:
Languages:  eng     Pagination:  443-7     Citation Subset:  IM    
Institute for Heart Research, Slovak Academy of Sciences, Bratislava, Slovak Republic.
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MeSH Terms
1-Phosphatidylinositol 3-Kinase / antagonists & inhibitors,  metabolism*
Androstadienes / pharmacology
Arrhythmias, Cardiac / enzymology,  etiology,  prevention & control*
Ischemic Preconditioning, Myocardial*
Myocardial Infarction / enzymology,  etiology,  prevention & control*
Myocardial Ischemia / complications,  enzymology,  therapy*
Myocardial Reperfusion Injury / enzymology,  etiology,  prevention & control*
Myocardium / enzymology*,  pathology
Protein Kinase Inhibitors / pharmacology
Proto-Oncogene Proteins c-akt / antagonists & inhibitors,  metabolism*
Rats, Wistar
Reg. No./Substance:
0/Androstadienes; 0/Protein Kinase Inhibitors; 19545-26-7/wortmannin; EC 3-Kinase; EC Proteins c-akt

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