Background
The proarrhythmic effect of the cardiac sympathetic nervous system has long been established. However, many aspects of the underlying pathophysiological mechanisms remain unclear and controversial. We aimed to characterize the activation and repolarization patterns of the ventricles under sympathetic stimulation in a sheep model, combining a 104-electrode sock for the epicardial surface and a 64-electrode mini-basket catheter with a 3D-Mapping System for the endocardium.

Methods
After lateral thoracotomy (n= 6 sheep) a custom-built multi-electrode sock (104 silver electrodes, spacing 1,2cm) (fig. B) was placed around the epicardium. Left Stellate ganglion stimulation (SGS) was performed at 5 Hz and the threshold current was set at a 10% increase in systolic arterial blood pressure. Epicardial sock electrode recordings and left ventricular intracardiac mapping using a 64-electrode mini-basket catheter (fig. A, C) were performed after 3 minutes of SGS at 1,5x threshold current. To achieve a homogenous activation front, the ventricles were paced epicardially at 130 bpm from a posterior basal septal stimulation site. Data were acquired and preprocessed using a 128-channel amplifier setup. 3D-Data of intracardiac Map and sock electrodes (fig. D) were fused (fig. E) using a custom-made software. The activation recovery interval (ARI) as a surrogate parameter for action potential duration was defined as the interval between minimal dV/dt of the depolarization wave and maximum dV/dt of the repolarization wave. The epicardium was divided into four basal, four midventricular regions (left anterior and posterior, right anterior and posterior) and one apical region.

Results
Under sympathetic stimulation we observed a prolongation of ARIs in the ventricular myocardium with a more distinct effect on the left sided ARIs than on the right sided ARIs (Control vs. SGS: Left anterior basal 234.6 ms vs. 245.5 ms, p=0.09; right anterior basal 242.6 ms vs. 249.6 ms, p= 0.03; left posterior basal 235.5 ms vs. 246.0 ms, p= 0.007; right posterior basal 245.4 ms vs. 252.2 ms p= 0.26; left anterior mid 236.4 ms vs. 250.6 ms, p=0.02; right anterior mid 242.7 ms vs. 253.3 ms p=0.02; left posterior mid 233.8 ms vs. 244.6 ms, p=0.007; right posterior mid 247.1 vs. 259.1 ms, p= 0.02; apex 240.5 ms vs 251.5 ms p=0.02 [fig. F]). Local repolarization times, being dependent on both activation time and action potential duration, did not differ significantly between groups. Total activation time was slightly longer under SGS (47.5ms vs 51.02 ms, p=0.03). Endo- and epicardial maps showed concordant earliest and latest basal activation sites.

Conclusion
Using a 3D-analysis tool for integration of simultaneous epi- and endocardial mapping we could show that left stellate ganglion stimulation lead to a marked increase in both left and right ventricular ARIs in our sheep model. This is in line with single cell data but has to be investigated further with respect to its role in arrhythmogenesis.