Document Detail


Reduced conduction reserve in the diabetic rat heart: role of iPLA2 activation in the response to ischemia.
MedLine Citation:
PMID:  21037228     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Hearts from streptozotocin (STZ)-induced diabetic rats have previously been shown to have impaired intercellular electrical coupling, due to reorganization (lateralization) of connexin43 proteins. Due to the resulting reduction in conduction reserve, conduction velocity in diabetic hearts is more sensitive to conditions that reduce cellular excitability or intercellular electrical coupling. Diabetes is a known risk factor for cardiac ischemia, a condition associated with both reduced cellular excitability and reduced intercellular coupling. Activation of Ca(2+)-independent phospholipase A(2) (iPLA(2)) is known to be part of the response to acute ischemia and may contribute to the intercellular uncoupling by causing increased levels of arachidonic acid and lysophosphatidyl choline. Normally perfused diabetic hearts are known to exhibit increased iPLA(2) activity and may thus be particularly sensitive to further activation of these enzymes. In this study, we used voltage-sensitive dye mapping to assess changes in conduction velocity in response to acute global ischemia in Langendorff-perfused STZ-induced diabetic hearts. Conduction slowing in response to ischemia was significantly larger in STZ-induced diabetic hearts compared with healthy controls. Similarly, slowing of conduction velocity in response to acidosis was also more pronounced in STZ-induced diabetic hearts. Inhibition of iPLA(2) activity using bromoenol lactone (BEL; 10 μM) had no effect on the response to ischemia in healthy control hearts. However, in STZ-induced diabetic hearts, BEL significantly reduced the amount of conduction slowing observed beginning 5 min after the onset of ischemia. BEL treatment also significantly increased the time to onset of sustained arrhythmias in STZ-induced diabetic hearts but had no effect on the time to arrhythmia in healthy control hearts. Thus, our results suggest that iPLA(2) activation in response to acute ischemia in STZ-induced diabetic hearts is more pronounced than in control hearts and that this response is a significant contributor to arrhythmogenic conduction slowing.
Authors:
Parisa Rahnema; Yakhin Shimoni; Anders Nygren
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-10-29
Journal Detail:
Title:  American journal of physiology. Heart and circulatory physiology     Volume:  300     ISSN:  1522-1539     ISO Abbreviation:  Am. J. Physiol. Heart Circ. Physiol.     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2011-01-04     Completed Date:  2011-01-28     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  H326-34     Citation Subset:  IM    
Affiliation:
Department of Electrical and Computer Engineering, University of Calgary, Calgary, Alberta, Canada.
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MeSH Terms
Descriptor/Qualifier:
Analysis of Variance
Animals
Arrhythmias, Cardiac / metabolism,  physiopathology
Diabetes Mellitus, Experimental / metabolism*,  physiopathology
Female
Heart / physiopathology*
Heart Conduction System / metabolism*,  physiopathology
Male
Myocardial Ischemia / metabolism*,  physiopathology
Myocardium / metabolism*
Phospholipases A2, Calcium-Independent / metabolism*
Rats
Rats, Sprague-Dawley
Grant Support
ID/Acronym/Agency:
//Canadian Institutes of Health Research
Chemical
Reg. No./Substance:
EC 3.1.1.4/Phospholipases A2, Calcium-Independent

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


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