Localized cardiomyocyte lipid accumulation is associated with slowed epicardial conduction in rats

SP Wells; AJA Raaijmakers; CL Curl; C O'Shea; S Hayes; KM Mellor; JM Kalman; P Kirchhof; D Pavlovic; LMD Delbridge; JR Bell

Journal article

Localized cardiomyocyte lipid accumulation is associated with slowed epicardial conduction in rats

SP Wells, AJA Raaijmakers, CL Curl, C O'Shea, S Hayes, KM Mellor, JM Kalman, P Kirchhof, D Pavlovic, LMD Delbridge, JR Bell

Journal of General Physiology | Published : 2023

DOI: 10.1085/jgp.202213296

Abstract

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..

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University of Melbourne Researchers

Hanneke Raaijmakers Author

Claire Curl Author

Kim Mellor Author

Jonathan Kalman Author

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Grants

Awarded by Wellcome Trust

Funding Acknowledgements

Jeanne M. Nerbonne served as editor.r MATLAB script for the generation of activation maps and conduction velocity analysis was kindly provided by Professor Cesare Terracciano, Imperial College London (London, UK), and is gratefully acknowledged. Technical support was provided by the Melbourne Histology Platform.r This research was supported by the National Health and Medical Research Council (grants #1099352 and #1125453; to L.M.D. Delbridge and J.R. Bell) and the Australian Research Council (grant #DP160102404; to L.M.D. Delbridge). D. Pavlovic is supported by the British Heart Foundation (PG/17/55/33087; RG/17/15/33106; FS/19/12/34204; FS/19/16/34169). C. O'Shea is supported by a Sir Henry Wellcome Fellowship, Wellcome Trust, 221650/Z/20/Z.r Author contributions: S.P. Wells, D. Pavlovic, L.M.D. Delbridge, and J.R. Bell designed the research; S.P. Wells, A.J.A. Raaijmakers, S. Hayes, and J.R. Bell performed experiments; S.P. Wells, A.J.A. Raaijmakers, C.L. Curl, C. O'Shea, S. Hayes, and J.R. Bell analyzed data; and S.P. Wells, K.M. Mellor, J.M. Kalman, L.M.D. Delbridge, and J.R. Bell wrote the paper. All authors approved the final version of the manuscript.