Document Detail


Adverse Remodeling of the Electrophysiological Response to Ischemia-Reperfusion in Human Heart Failure Is Associated with Remodeling of Metabolic Gene Expression.
MedLine Citation:
PMID:  25114062     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
BACKGROUND: -Ventricular arrhythmias occur more frequently in heart failure during episodes of ischemia-reperfusion (I-R), although the mechanisms underlying this in humans are unclear. We assessed, in explanted human hearts, the remodeled electrophysiological response to acute I-R in heart failure, and its potential causes, including the remodeling of metabolic gene expression.
METHODS AND RESULTS: -We optically mapped coronary-perfused left ventricular wedge preparations from 6 human end-stage failing hearts (F) and 6 donor hearts rejected for transplantation (D). Preparations were subjected to 30 minutes of global ischemia, followed by 30 minutes of reperfusion. Failing hearts had exaggerated electrophysiological responses to I-R, with greater action potential duration (APD) shortening (p<0.001 at 8 minutes ischemia; p=0.001 at 12 minutes ischemia) and greater conduction slowing during ischemia, delayed recovery of electrical excitability following reperfusion (F 4.8±1.8 vs. D 1.0±0 mins, p<0.05), and incomplete restoration of APD and conduction velocity early after reperfusion. Expression of 46 metabolic genes were probed using custom-designed TaqMan arrays, using extracted RNA from 15 failing and 9 donor hearts. Ten genes important in cardiac metabolism were downregulated in heart failure, with SLC27A4 and KCNJ11 significantly downregulated at a false discovery rate of 0%.
CONCLUSIONS: -We demonstrate, for the first time in human hearts, that the electrophysiological response to I-R in heart failure is accelerated during ischemia with slower recovery following reperfusion. This can enhance spatial conduction and repolarization gradients across the ischemic border and increase arrhythmia susceptibility. This adverse response was associated with downregulation of expression of cardiac metabolic genes.
Authors:
Fu Siong Ng; Katherine M Holzem; Aaron C Koppel; Deborah Janks; Fabiana Gordon; Andrew L Wit; Nicholas S Peters; Igor R Efimov
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-8-11
Journal Detail:
Title:  Circulation. Arrhythmia and electrophysiology     Volume:  -     ISSN:  1941-3084     ISO Abbreviation:  Circ Arrhythm Electrophysiol     Publication Date:  2014 Aug 
Date Detail:
Created Date:  2014-8-12     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101474365     Medline TA:  Circ Arrhythm Electrophysiol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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