title: Conduction and refractory disorders in the diabetic atrium.
abstract: Diabetes mellitus (DM) is an independent risk of atrial fibrillation. However, its arrhythmogenic substrates remain unclear. This study sought to examine the precise propagation and the spatiotemporal dispersion of the action potential (AP) in the diabetic atrium. DM was induced by streptozotocin (65 mg/kg) in 8-wk-old male Wister rats. Optical mapping and histological analysis were performed in the right atrium (RA) from control (n = 26) and DM (n = 27) rats after 16 wk. Rate-dependent alterations of conduction velocity (CV) and its heterogeneity and the spatial distribution of AP were measured in RA using optical mapping. The duration of atrial tachyarrhythmia (AT) induced by rapid atrial stimulation was longer in DM (2.4 ± 0.6 vs. 0.9 ± 0.3 s, P < 0.05). CV was decreased, and its heterogeneity was greater in DM than control. Average action potential duration of 80% repolarization (APD(80)) at pacing cycle length (PCL) of 200 ms from four areas within the RA was prolonged (53 ± 2 vs. 40 ± 3 ms, P < 0.01), and the coefficient of variation of APD(80) was greater in DM than control (0.20 ± 0.02 vs. 0.15 ± 0.01%, P < 0.05). The ratio of APD(80) at PCL shorter than 200 ms to that at 200 ms was smaller (P < 0.001), and the incidence of APD alternans was higher in DM than control (100 vs. 0%, P < 0.001). Interstitial fibrosis was greater and connexin 40 expression was lower in DM than control. The remodeling of the diabetic atrium was characterized as follows: greater vulnerability to AT, increased conduction slowing and its heterogeneity, the prolongation of APD, the increase in spatial dispersion and frequency-dependent shortening of APD, and increased incidence of APD alternans.
authors.affiliation: Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Masaya
authors.initials: M
authors.lastname: Watanabe
authors.forename: Hisashi
authors.initials: H
authors.lastname: Yokoshiki
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Mitsuyama
authors.forename: Kazuya
authors.initials: K
authors.lastname: Mizukami
authors.forename: Taisuke
authors.initials: T
authors.lastname: Ono
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tsutsui
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D015153:Blotting, Western; D002304:Cardiac Pacing, Artificial; D017630:Connexins / Q000096:biosynthesis; D003627:Data Interpretation, Statistical; D003921:Diabetes Mellitus, Experimental / Q000473:pathology / Q000503:physiopathology*; D004558:Electric Stimulation; D004562:Electrocardiography; D005355:Fibrosis; D006321:Heart / Q000503:physiopathology*; D006325:Heart Atria / Q000503:physiopathology; D006329:Heart Conduction System / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D009206:Myocardium / Q000473:pathology; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar; D012032:Refractory Period, Electrophysiological / Q000502:physiology*; D013610:Tachycardia / Q000503:physiopathology; D000097003:Gap Junction alpha-5 Protein
chemical_list: D001786:Blood Glucose; D017630:Connexins; D000097003:Gap Junction alpha-5 Protein