A Controllable Canine Model Of Mitral Regurgitation To Study Mechanical And Electrical Remodeling Of The Atria
Chawannuch Ruaengsri1, Matthew R. Schill1, Timothy S. Lancaster1, Jason W. Greenberg2, Spencer J. Melby1, Richard B. Schuessler1, Ralph J. Damiano, Jr.1.
1Washington University in St. Louis, St. Louis, MO, USA, 2Saint Louis University, St. Louis, MO, USA.
OBJECTIVE: : Atrial fibrillation (AF) occurs in up to 30% of patients with mitral regurgitation (MR) referred for valve surgery. However, the mechanisms of AF in MR are poorly understood. The purpose of this study was to determine the effects of chronic left atrial (LA) volume overload on atrial anatomy, hemodynamics and electrophysiology using a ventriculoatrial shunt in a canine model.
METHODS: Eleven normal canines underwent implantation of a shunt between the left ventricular (LV) apex and the LA appendage. Shunt fraction was titrated to 40-50% of cardiac output. Eight canines underwent a sham procedure. At baseline and at 6 months, an epicardial plaque with 250 bipolar electrodes was used to determine atrial activation times (AT) and effective refractory periods (ERP) on the LA and right atrium (RA). Biatrial and systemic pressures, aortic and shunt flow, AF duration and inducibility were recorded at baseline and six months. LA and LV diameters and volumes were determined using transesophageal echocardiography.
RESULTS: baseline, there were no difference between the sham and shunt group in any physiological variable measured. Mean shunt fraction was 45±8%. At six months, LA pressure increased from 10.8±3.3 to 13±3.1 mmHg, p<0.001. LA diameter increased from 2.96±0.1 to 4.13±0.1cm (p<0.001) and LV ejection fraction decreased from 65±2 to 54±3% (p<0.001, Figure). Induced AF duration was 224±288 s compared to 16±17 s in the sham group (p=0.009). There was a trend toward longer AT in the shunt group versus the sham group (71±13 vs 62±3 ms, p=0.06). The average RA and LA ERP were shorter in the shunt group compared to sham (RAERP: 151±21 vs 138±14 ms, p=0.12, LAERP: 150±17 vs 134±1 ms, p=0.035).
CONCLUSIONS: This model reproduces the physiologic remodeling seen in clinical MR. LA size increased, with a corresponding decrease in LV systolic function. These changes were associated with increased AT, lower ERP, and increased AF inducibility. This model provides a means to understand the dynamic proarrhythmic remodeling by which MR causes AF.
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