Alteraciones estructurales precoces asociadas al remodelado eléctrico de la fibrilación auricular en un modelo canino de estimulación auricular sostenida a altas frecuencias. Efecto protector del Irbesartán

Abstract

Introduction and objectives: Recent studies in animal models have shown that angiotensin II antagonists prevent the electric remodeling in atrial fibrillation (AF). The structural changes of the atrial wall in the early stages of atrial electric remodeling and the impact of irbesartan, an antagonist of the AT-1 angiotensin II receptor on these changes have not been systematically analized. Methods: Continous atrial stimulation at 400 bpm was performed for 3 days in 8 dogs. Another 4 dogs in sinus rhythm constituted the control group. All of the dogs were Beagles. Four of the stimulated dogs were pre-treated two days before and during all of the stimulation period with 2 mg/kg/day of irbesartan. The effective atrial refractary period (EARP) was determined basaly and on day 3, when atrial tissue samples were obtained for hystological examination. We quantified the percentage of myolisis of the atrial wall, as well as structural and ultrastructural changes using optic and electronic microscopy. Results: It was stated that non-treated animals stimulated for 3 days showed a significant reduction in EARP in relation to the controls (80±30 ms vs 137±12 ms). However, dogs treated with irbesartan showed an EARP similar to controls. Besides, irbesartan attenuated the structural changes of the atrial wall induced by stimulation, and reduced the percentage of severely damaged myocytes (21,0±2,4% vs 16,6±1,2%, p<0,05). Conclusions: Our study shows that irbesartan attenuates structural and electric changes in atrial myocardium associated to the initial stages of atrial remodeling in AF. The use of AT-1 receptor antagonists can be effective to prevent recurrences in patients with AF.