TY - JOUR
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 - Publisher Copyright:
© 2017 The Authors.
PY - 2017/9/1
Y1 - 2017/9/1
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
UR - http://www.scopus.com/inward/record.url?scp=85029758791&partnerID=8YFLogxK
U2 - 10.1161/JAHA.117.006717
DO - 10.1161/JAHA.117.006717
M3 - Article
C2 - 28919580
AN - SCOPUS:85029758791
SN - 2047-9980
VL - 6
JO - Journal of the American Heart Association
JF - Journal of the American Heart Association
IS - 9
M1 - e006717
ER -