Abstract 11069: Alogliptin, a Dipeptidyl Peptidase-4 Inhibitor Improves Ventricular Tachypacing-Induced Atrial Fibrillation in a Rabbit Model
Introduction: Dipeptidyl peptidase-4 (DPP-4) inhibitors, prescribed for type 2 diabetes mellitus, are recently reported to have cardioprotective effects via improving ventricular function. However, the role of DPP-4 inhibition in atrial remodeling, especially arrhythmogenic substrate, remains unclear. Therefore, we investigated the effects of a DPP-4 inhibitor, alogliptin, on atrial fibrillation (AF) caused by ventricular tachypacing (VTP) in a rabbit model.
Methods: New Zealand white rabbits (male, 2.8-3.1kg) were exposed to VTP (380-400 ppm) for 3 weeks using an implanted right ventricular pacemaker and fed/treated with or without alogliptin (20mg/kg/day). Three weeks later, rabbits were assessed by echocardiography, electrophysiological study and atrial histological analysis (Masson-trichrome staining for fibrosis and anti-CD31 immunofluorescence staining for capillary density). Moreover, expression of atrial angiogenic factors were determined by Western blot.
Results: AF was induced by atrial burst pacing in electrophysiological study. VTP rabbits exhibited a prolongation of AF duration, while alogliptin treatment attenuated it (8.8±2.3 seconds vs 2.4±0.3 seconds, p<0.05). Alogliptin also reduced the extent of atrial fibrosis in response to VTP (10.8%±1.0% vs 6.6%±1.1%, p<0.05). In addition, VTP rabbits treated with alogliptin displayed a 1.6-fold increase in capillary density of the left atrial myocardium compared with those without treatment. Western blot analysis indicated that the phosphorylation ratio of eNOS in arrhythmic left atrium was twice higher in alogliptin-treated rabbits compared with control. However, in echocardiography, rabbits treated with alogliptin did not show improvement in left atrial enlargement and left ventricular systolic dysfunction caused by VTP.
Conclusions: Alogliptin disrupted the process of AF promotion caused by the accumulation of fibrotic atrial tissue through augmenting atrial angiogenesis and improving endothelial function. Our findings suggest that DPP-4 inhibitors may be useful for the prevention of VTP-induced AF.
Author Disclosures: T. Yamamoto: None. M. Shimano: None. Y. Inden: None. N. Yoshida: None. S. Ishikawa: None. S. Okumura: None. H. Kato: None. S. Yanagisawa: None. T. Nagao: None. T. Ito: None. Y. Mizutani: None. Y. Tsuji: None. M. Hirai: None. T. Murohara: None.
- © 2014 by American Heart Association, Inc.