0305 : Heterogeneous conduction properties in the pig right ventricle

Abstract

The right ventricular outflow tract (RVOT) has a distinct embryological origin and is a common anatomical source of arrhythmias in the healthy and diseased myocardium. We hypothesised that specific RVOT activation and conduction properties may underlie the preferential RVOT origin of arrhythmias. Pig right ventricular (RV) wedge preparations were perfused via the left anterior descending and right coronary arteries. Electrical activation and conduction properties were obtained by optical mapping of the epicardial surface (di-4- ANEPPS 10μM) upon electrical stimulation of the preparation. Transmural needles were inserted in the RV free wall and RVOT and unipolar electrograms (EGMs) were recorded. Fiber orientation was obtained by diffusion tensor MRI. Regional mRNA expression was determined by RT-PCR and fibrosis was assessed histologically. Longitudinal and transverse conduction velocities were significantly reduced in RVOT compared to RV free wall (P<0.01). A different direction of propagation was observed in the RVOT compared to the RV free wall and a line of slowed propagation was found at the interface between the 2 regions. This was consistent with a 135±2° change in fiber orientation observed between the 2 regions within a restricted distance (<6cm). The RVOT showed more sites with fractionated EGMs (P<0.01) and more deflections per electrode (P<0.001) than the RV free wall. In line with these findings, a decreased expression of Scna5 and Gja1 was found in the RVOT compared to the RV free wall (P<0.001). Moreover, the RVOT was characterized by an upregulation of type I collagen mRNA, a higher collagen content (P<0.05) and the presence of fat infiltrations which were absent in the free wall. Conduction is slower in the pig RVOT and is associated with fractionated unipolar electrograms. Conduction slowing was related to (i) reduced connexin and sodium channel expression and (ii) region-specific structural properties which may generate a substrate for RVOT arrhythmias.