Concomitant obesity and metabolic syndrome add to the atrial arrhythmogenic phenotype in male hypertensive rats

Mathias Hohl; Dennis H. Lau; Andreas Müller; Adrian D. Elliott; Benedikt Linz; Rajiv Mahajan; Jeroen M.L. Hendriks; Michael Böhm; Ulrich Schotten; Prashanthan Sanders; Dominik Linz

doi:10.1161/JAHA.117.006717

Concomitant obesity and metabolic syndrome add to the atrial arrhythmogenic phenotype in male hypertensive rats

Mathias Hohl, Dennis H. Lau, Andreas Müller, Adrian D. Elliott, Benedikt Linz, Rajiv Mahajan, Jeroen M.L. Hendriks, Michael Böhm, Ulrich Schotten, Prashanthan Sanders, Dominik Linz

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Abstract

Background--Besides hypertension, obesity and the metabolic syndrome have recently emerged as risk factors for atrial fibrillation. This study sought to delineate the development of an arrhythmogenic substrate for atrial fibrillation in hypertension with and without concomitant obesity and metabolic syndrome. Methods and Results--We compared obese spontaneously hypertensive rats (SHR-obese, n = 7-10) with lean hypertensive controls (SHR-lean, n = 7-10) and normotensive rats (n = 7-10). Left atrial emptying function (MRI) and electrophysiological parameters were characterized before the hearts were harvested for histological and biochemical analyses. At the age of 38 weeks, SHR-obese, but not SHR-lean, showed increased body weight and impaired glucose tolerance together with dyslipidemia compared with normotensive rats. Mean blood pressure was similarly increased in SHR-lean and SHR-obese when compared with normotensive rats (178±9 and 180±8 mm Hg [not significant] versus 118±5 mm Hg, P < 0.01 for both), but left ventricular enddiastolic pressure was more increased in SHR-obese than in SHR-lean. Impairment of left atrial emptying function, increase in total atrial activation time, and conduction heterogeneity, as well as prolongation of inducible atrial fibrillation durations, were more pronounced in SHR-obese as compared with SHR-lean. Histological and biochemical examinations revealed enhanced triglycerides and more pronounced fibrosis in the left atrium of SHR-obese. Besides increased expression of profibrotic markers in SHR-lean and SHR-obese, the profibrotic extracellular matrix protein osteopontin was highly upregulated only in SHR-obese. Conclusions--In addition to hypertension alone, concomitant obesity and metabolic syndrome add to the atrial arrhythmogenic phenotype by impaired left atrial emptying function, local conduction abnormalities, interstitial atrial fibrosis formation, and increased propensity for atrial fibrillation.

Original language	English
Article number	e006717
Number of pages	12
Journal	Journal of the American Heart Association
Volume	6
Issue number	9
DOIs	https://doi.org/10.1161/JAHA.117.006717
Publication status	Published - 17 Sept 2017
Externally published	Yes

Bibliographical note

© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.
This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Keywords

Atrial fibrillation
Hypertension
Metabolic syndrome
Obesity

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Hohl_Concomitant_P2017Final published version, 1.78 MBLicence: CC BY-NC

Cite this

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title = "Concomitant obesity and metabolic syndrome add to the atrial arrhythmogenic phenotype in male hypertensive rats",

abstract = "Background--Besides hypertension, obesity and the metabolic syndrome have recently emerged as risk factors for atrial fibrillation. This study sought to delineate the development of an arrhythmogenic substrate for atrial fibrillation in hypertension with and without concomitant obesity and metabolic syndrome. Methods and Results--We compared obese spontaneously hypertensive rats (SHR-obese, n = 7-10) with lean hypertensive controls (SHR-lean, n = 7-10) and normotensive rats (n = 7-10). Left atrial emptying function (MRI) and electrophysiological parameters were characterized before the hearts were harvested for histological and biochemical analyses. At the age of 38 weeks, SHR-obese, but not SHR-lean, showed increased body weight and impaired glucose tolerance together with dyslipidemia compared with normotensive rats. Mean blood pressure was similarly increased in SHR-lean and SHR-obese when compared with normotensive rats (178±9 and 180±8 mm Hg [not significant] versus 118±5 mm Hg, P < 0.01 for both), but left ventricular enddiastolic pressure was more increased in SHR-obese than in SHR-lean. Impairment of left atrial emptying function, increase in total atrial activation time, and conduction heterogeneity, as well as prolongation of inducible atrial fibrillation durations, were more pronounced in SHR-obese as compared with SHR-lean. Histological and biochemical examinations revealed enhanced triglycerides and more pronounced fibrosis in the left atrium of SHR-obese. Besides increased expression of profibrotic markers in SHR-lean and SHR-obese, the profibrotic extracellular matrix protein osteopontin was highly upregulated only in SHR-obese. Conclusions--In addition to hypertension alone, concomitant obesity and metabolic syndrome add to the atrial arrhythmogenic phenotype by impaired left atrial emptying function, local conduction abnormalities, interstitial atrial fibrosis formation, and increased propensity for atrial fibrillation.",

keywords = "Atrial fibrillation, Hypertension, Metabolic syndrome, Obesity",

author = "Mathias Hohl and Lau, {Dennis H.} and Andreas M{\"u}ller and Elliott, {Adrian D.} and Benedikt Linz and Rajiv Mahajan and Hendriks, {Jeroen M.L.} and Michael B{\"o}hm and Ulrich Schotten and Prashanthan Sanders and Dominik Linz",

note = " {\textcopyright} 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.",

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doi = "10.1161/JAHA.117.006717",

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T1 - Concomitant obesity and metabolic syndrome add to the atrial arrhythmogenic phenotype in male hypertensive rats

AU - Hohl, Mathias

AU - Lau, Dennis H.

AU - Müller, Andreas

AU - Elliott, Adrian D.

AU - Linz, Benedikt

AU - Mahajan, Rajiv

AU - Hendriks, Jeroen M.L.

AU - Böhm, Michael

AU - Schotten, Ulrich

AU - Sanders, Prashanthan

AU - Linz, Dominik

N1 - © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

PY - 2017/9/17

Y1 - 2017/9/17

N2 - Background--Besides hypertension, obesity and the metabolic syndrome have recently emerged as risk factors for atrial fibrillation. This study sought to delineate the development of an arrhythmogenic substrate for atrial fibrillation in hypertension with and without concomitant obesity and metabolic syndrome. Methods and Results--We compared obese spontaneously hypertensive rats (SHR-obese, n = 7-10) with lean hypertensive controls (SHR-lean, n = 7-10) and normotensive rats (n = 7-10). Left atrial emptying function (MRI) and electrophysiological parameters were characterized before the hearts were harvested for histological and biochemical analyses. At the age of 38 weeks, SHR-obese, but not SHR-lean, showed increased body weight and impaired glucose tolerance together with dyslipidemia compared with normotensive rats. Mean blood pressure was similarly increased in SHR-lean and SHR-obese when compared with normotensive rats (178±9 and 180±8 mm Hg [not significant] versus 118±5 mm Hg, P < 0.01 for both), but left ventricular enddiastolic pressure was more increased in SHR-obese than in SHR-lean. Impairment of left atrial emptying function, increase in total atrial activation time, and conduction heterogeneity, as well as prolongation of inducible atrial fibrillation durations, were more pronounced in SHR-obese as compared with SHR-lean. Histological and biochemical examinations revealed enhanced triglycerides and more pronounced fibrosis in the left atrium of SHR-obese. Besides increased expression of profibrotic markers in SHR-lean and SHR-obese, the profibrotic extracellular matrix protein osteopontin was highly upregulated only in SHR-obese. Conclusions--In addition to hypertension alone, concomitant obesity and metabolic syndrome add to the atrial arrhythmogenic phenotype by impaired left atrial emptying function, local conduction abnormalities, interstitial atrial fibrosis formation, and increased propensity for atrial fibrillation.

AB - Background--Besides hypertension, obesity and the metabolic syndrome have recently emerged as risk factors for atrial fibrillation. This study sought to delineate the development of an arrhythmogenic substrate for atrial fibrillation in hypertension with and without concomitant obesity and metabolic syndrome. Methods and Results--We compared obese spontaneously hypertensive rats (SHR-obese, n = 7-10) with lean hypertensive controls (SHR-lean, n = 7-10) and normotensive rats (n = 7-10). Left atrial emptying function (MRI) and electrophysiological parameters were characterized before the hearts were harvested for histological and biochemical analyses. At the age of 38 weeks, SHR-obese, but not SHR-lean, showed increased body weight and impaired glucose tolerance together with dyslipidemia compared with normotensive rats. Mean blood pressure was similarly increased in SHR-lean and SHR-obese when compared with normotensive rats (178±9 and 180±8 mm Hg [not significant] versus 118±5 mm Hg, P < 0.01 for both), but left ventricular enddiastolic pressure was more increased in SHR-obese than in SHR-lean. Impairment of left atrial emptying function, increase in total atrial activation time, and conduction heterogeneity, as well as prolongation of inducible atrial fibrillation durations, were more pronounced in SHR-obese as compared with SHR-lean. Histological and biochemical examinations revealed enhanced triglycerides and more pronounced fibrosis in the left atrium of SHR-obese. Besides increased expression of profibrotic markers in SHR-lean and SHR-obese, the profibrotic extracellular matrix protein osteopontin was highly upregulated only in SHR-obese. Conclusions--In addition to hypertension alone, concomitant obesity and metabolic syndrome add to the atrial arrhythmogenic phenotype by impaired left atrial emptying function, local conduction abnormalities, interstitial atrial fibrosis formation, and increased propensity for atrial fibrillation.

KW - Atrial fibrillation

KW - Hypertension

KW - Metabolic syndrome

KW - Obesity

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Concomitant obesity and metabolic syndrome add to the atrial arrhythmogenic phenotype in male hypertensive rats

Abstract

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