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Localized cardiomyocyte lipid accumulation is associated with slowed epicardial conduction in rats.
Wells, Simon P; Raaijmakers, Antonia J A; Curl, Claire L; O'Shea, Christopher; Hayes, Sarah; Mellor, Kimberley M; Kalman, Jonathan M; Kirchhof, Paulus; Pavlovic, Davor; Delbridge, Lea M D; Bell, James R.
Afiliação
  • Wells SP; Department of Anatomy and Physiology, University of Melbourne, Parkville, Australia.
  • Raaijmakers AJA; Institute of Cardiovascular Sciences, University of Birmingham , Birmingham, UK.
  • Curl CL; Department of Anatomy and Physiology, University of Melbourne, Parkville, Australia.
  • O'Shea C; Department of Anatomy and Physiology, University of Melbourne, Parkville, Australia.
  • Hayes S; Institute of Cardiovascular Sciences, University of Birmingham , Birmingham, UK.
  • Mellor KM; Department of Microbiology, Anatomy, Physiology and Pharmacology, La Trobe University, Bundoora, Australia.
  • Kalman JM; Department of Anatomy and Physiology, University of Melbourne, Parkville, Australia.
  • Kirchhof P; Department of Physiology, University of Auckland, Auckland, New Zealand.
  • Pavlovic D; Auckland Bioengineering Institute, University of Auckland , Auckland, New Zealand.
  • Delbridge LMD; Department of Cardiology, Royal Melbourne Hospital, Melbourne, Australia.
  • Bell JR; Department of Medicine, University of Melbourne, Melbourne, Australia.
J Gen Physiol ; 155(11)2023 Nov 06.
Article em En | MEDLINE | ID: mdl-37787979
Transmural action potential duration differences and transmural conduction gradients aid the synchronization of left ventricular repolarization, reducing vulnerability to transmural reentry and arrhythmias. A high-fat diet and the associated accumulation of pericardial adipose tissue are linked with conduction slowing and greater arrhythmia vulnerability. It is predicted that cardiac adiposity may more readily influence epicardial conduction (versus endocardial) and disrupt normal transmural activation/repolarization gradients. The aim of this investigation was to determine whether transmural conduction gradients are modified in a rat model of pericardial adiposity. Adult Sprague-Dawley rats were fed control/high-fat diets for 15 wk. Left ventricular 300 µm tangential slices were generated from the endocardium to the epicardium, and conduction was mapped using microelectrode arrays. Slices were then histologically processed to assess fibrosis and cardiomyocyte lipid status. Conduction velocity was significantly greater in epicardial versus endocardial slices in control rats, supporting the concept of a transmural conduction gradient. High-fat diet feeding increased pericardial adiposity and abolished the transmural conduction gradient. Slowed epicardial conduction in epicardial slices strongly correlated with an increase in cardiomyocyte lipid content, but not fibrosis. The positive transmural conduction gradient reported here represents a physiological property of the ventricular activation sequence that likely protects against reentry. The absence of this gradient, secondary to conduction slowing and cardiomyocyte lipid accumulation, specifically in the epicardium, indicates a novel mechanism by which pericardial adiposity may exacerbate ventricular arrhythmias.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Miócitos Cardíacos / Sistema de Condução Cardíaco Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Animals Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Miócitos Cardíacos / Sistema de Condução Cardíaco Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Animals Idioma: En Ano de publicação: 2023 Tipo de documento: Article