Comorbid Obesity and Metabolic Syndrome Add to the Atrial Arrhythmogenic Phenotype in Hypertensive Rats

Abstract

Introduction: Besides hypertension alone, comorbid obesity and the metabolic syndrome are emerging risk factors for atrial fibrillation (AF). This study sought to delineate the development of global electrophysiological and structural substrate for AF in hypertension with and without obesity and metabolic syndrome. Methods: We compared an obese spontaneously hypertensive rat model (SHR-ob, n = 10) with lean spontaneously hypertensive rats (SHR-lean, n = 10) and normotensive controls (Ctr, n = 10). Left atrial (LA) emptying function (magnetic resonance imaging) and atrial electrophysiological parameters were measured before the hearts were harvested for histological and biochemical analysis. Results: At the age of 39 weeks, SHR-ob, but not SHR-lean and Ctr, showed impaired glucose tolerance and increased body-weight together with dyslipidaemia. Systolic blood pressure was similarly increased in SHR-lean and SHR-ob when compared to Ctr (252 ± 7 and 242 ± 7 mmHg (n.s.), vs. 155 ± 2 mmHg, p < 0.01 for both). Compared to Ctr, impairment of LA emptying function, rise in total atrial activation time and regions of slow conduction as well as prolongation of inducible AF-duration were more pronounced in SHR-ob than in SHR-lean. Histological and biochemical examinations revealed a more pronounced increase in LA fibrosis and LA gene expression of profibrotic markers like osteopontin, connective tissue growth factor (cTGF) and transforming growth factor (TGF)-β1 and advanced glycation endproduct content in SHR-ob compared to SHR-lean. Conclusions: In addition to hypertension alone, comorbid obesity and metabolic syndrome adds to the atrial arrhythmogenic phenotype by impaired LA-emptying function, conduction abnormalities, interstitial atrial fibrosis, increased profibrotic gene expression and increased propensity for AF.