title: Electrical remodeling in the failing heart.
abstract: OBJECTIVE
  We focus on the molecular and cellular basis of excitability, conduction and electrical remodeling in heart failure with dyssynchronous left ventricular contraction (DHF) and its restoration by cardiac resynchronization therapy (CRT) using a canine tachy-pacing heart failure model.
  
  
  RESULTS
  The electrophysiological hallmark of cells and tissues isolated from failing hearts is prolongation of action potential duration (APD) and conduction slowing. In human studies and a number of animal models of heart failure, functional downregulation of K currents and alterations in depolarizing Na and Ca currents and transporters are demonstrated. Alterations in intercellular ion channels and extracellular matrix contribute to heterogeneity of APD and conduction slowing. The changes in cellular and tissue function are regionally heterogeneous, particularly in the DHF. Furthermore, beta-adrenergic signaling and modulation of ionic currents is blunted in heart failure. CRT partially reverses the DHF-induced downregulation of K current and improves Na channel gating. CRT significantly improves Ca homeostasis, especially in lateral myocytes, and restores the DHF-induced blunted beta-adrenergic receptor responsiveness. CRT abbreviates DHF-induced prolongation of APD in the lateral myocytes, reduces the left ventricular regional gradient of APD and suppresses development of early afterdepolarizations.
  
  
  CONCLUSIONS
  CRT partially restores DHF-induced electrophysiological remodeling, abnormal Ca homeostasis, blunted beta-adrenergic responsiveness, and regional heterogeneity of APD, and thus may suppress ventricular arrhythmias and contribute to the mortality benefit of CRT as well as improving mechanical performance of the heart.
authors.affiliation: Department of Cardiology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Aiba
authors.forename: Gordon F
authors.initials: GF
authors.lastname: Tomaselli
mesh_terms: D000200:Action Potentials; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002304:Cardiac Pacing, Artificial; D017630:Connexins / Q000378:metabolism; D015870:Gene Expression; D006329:Heart Conduction System / Q000503:physiopathology*; D006333:Heart Failure / Q000378:metabolism / Q000503:physiopathology* / Q000628:therapy; D006801:Humans; D011188:Potassium / Q000378:metabolism; D012964:Sodium / Q000378:metabolism
chemical_list: D017630:Connexins; D012964:Sodium; D011188:Potassium; D002118:Calcium