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Temporal alterations and cellular mechanisms of transmural repolarization during progression of mouse cardiac hypertrophy and failure.
MedLine Citation:
PMID:  23356774     Owner:  NLM     Status:  Publisher    
AIM: The remodeling of transmural dispersion of repolarization (TDR) in human heart failure (HF) and in different animal models of cardiac hypertrophy or HF remains a controversial topic. We hypothesize that TDR may exhibit temporal alterations, depending on the stage of the disease. METHODS: We systematically investigated the temporal alterations of TDR during the development of cardiac hypertrophy and HF in the mouse pressure-overload model using electrophysiological and molecular biology techniques. RESULTS: A progressive prologation of QT interval and changes in the amplitude of the J wave at 2-, 5-, 9-, and 13-weeks in anesthetized aorta-banded mice. Action potential duration (APD) at 90% repolarization (APD(90) ) in subendocardial myocytes of the left ventricular free wall remained unchanged at the hypertrophic stage (2- and 5-weeks), but was significantly prolonged in HF mice at 9 and 13 weeks. However, APD(90) in subepicardial myocytes exhibited a significant prolongation at 2-weeks, and did not progressively extend from 2-weeks to 13-weeks in banded mice. Thus, non-parallel prolongation of APD in subendocardial and subepicardial myocytes led to a reduction of TDR at hypertrophic stage and an amplification of TDR at HF stage. Further experiments revealed that asynchronous down-regulation of voltage-dependent potassium currents (I(to,f) , I(K) (,slow) and I(ss) ) and L-type calcium currents (I(C) (a-L) ) in subendocardial and subepicardial myocytes may contribute to the dynamic remodeling of transmural APD. CONCLUSION: The two distinct TDR modes were revealed during the progression of mouse cardiac hypertrophy and failure, indicating that the remodeling of TDR depends on the stage of the disease. Acta Physiologica © 2013 Scandinavian Physiological Society.
Chenxia Shi; Xiaofeng Wang; Fang Dong; Yuhong Wang; Jingfang Hui; Zhige Lin; Jing Yang; Yanfang Xu
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-29
Journal Detail:
Title:  Acta physiologica (Oxford, England)     Volume:  -     ISSN:  1748-1716     ISO Abbreviation:  Acta Physiol (Oxf)     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-29     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101262545     Medline TA:  Acta Physiol (Oxf)     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Acta Physiologica © 2013 Scandinavian Physiological Society.
The Key Laboratory of Neural and Vascular Biology, Ministry of Education;The Key Laboratory of New Drug Pharmacology and Toxicology, Department of Pharmacology, Hebei Medical University, Shijiazhuang, 050017, Hebei Province, China.
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