| Reduced susceptibility to ischemia-induced arrhythmias in the preconditioned rat heart is independent of PI3-kinase/Akt. | |
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MedLine Citation:
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PMID: 19627174 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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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Authors:
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T RAVINGEROVA; J MATEJIKOVA; D PANCZA; F KOLAR |
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Publication Detail:
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Type: In Vitro; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Physiological research / Academia Scientiarum Bohemoslovaca Volume: 58 ISSN: 0862-8408 ISO Abbreviation: Physiol Res Publication Date: 2009 |
Date Detail:
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Created Date: 2009-07-24 Completed Date: 2009-09-02 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 9112413 Medline TA: Physiol Res Country: Czech Republic |
Other Details:
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Languages: eng Pagination: 443-7 Citation Subset: IM |
Affiliation:
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Institute for Heart Research, Slovak Academy of Sciences, Bratislava, Slovak Republic. usrdravi@savba.sk |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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1-Phosphatidylinositol 3-Kinase
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antagonists & inhibitors,
metabolism* Androstadienes / pharmacology Animals Arrhythmias, Cardiac / enzymology, etiology, prevention & control* Ischemic Preconditioning, Myocardial* Male Myocardial Infarction / enzymology, etiology, prevention & control* Myocardial Ischemia / complications, enzymology, therapy* Myocardial Reperfusion Injury / enzymology, etiology, prevention & control* Myocardium / enzymology*, pathology Perfusion Protein Kinase Inhibitors / pharmacology Proto-Oncogene Proteins c-akt / antagonists & inhibitors, metabolism* Rats Rats, Wistar |
| Chemical | |
Reg. No./Substance:
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0/Androstadienes; 0/Protein Kinase Inhibitors; 19545-26-7/wortmannin; EC 2.7.1.137/1-Phosphatidylinositol 3-Kinase; EC 2.7.11.1/Proto-Oncogene Proteins c-akt |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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