Localized cardiomyocyte lipid accumulation is associated with slowed epicardial conduction in rats
Standard
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.
In: J GEN PHYSIOL, Vol. 155, No. 11, e202213296, 06.11.2023.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - Localized cardiomyocyte lipid accumulation is associated with slowed epicardial conduction in rats
AU - Wells, Simon P
AU - Raaijmakers, Antonia J A
AU - Curl, Claire L
AU - O'Shea, Christopher
AU - Hayes, Sarah
AU - Mellor, Kimberley M
AU - Kalman, Jonathan M
AU - Kirchhof, Paulus
AU - Pavlovic, Davor
AU - Delbridge, Lea M D
AU - Bell, James R
N1 - © 2023 Wells et al.
PY - 2023/11/6
Y1 - 2023/11/6
N2 - 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.
AB - 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.
KW - Animals
KW - Rats
KW - Myocytes, Cardiac
KW - Heart Conduction System/physiology
KW - Rats, Sprague-Dawley
KW - Arrhythmias, Cardiac
KW - Lipids
KW - Action Potentials/physiology
U2 - 10.1085/jgp.202213296
DO - 10.1085/jgp.202213296
M3 - SCORING: Journal article
C2 - 37787979
VL - 155
JO - J GEN PHYSIOL
JF - J GEN PHYSIOL
SN - 0022-1295
IS - 11
M1 - e202213296
ER -