Arrhythmogenic substrate in deep intra-trabecular structures of RVOT
endocardium in canine model of Brugada syndrome
Introduction: A prominent action potential (AP) notch in
the epicardium (Epi) of the RVOT is known to predispose to the
development of closely-coupled phase 2 reentrant extrasystoles, capable
of precipitating ventricular tachycardia and fibrillation (VT/VF) in the
setting of BrS. Ablation of this Epi substrate exerts an ameliorative
effect. In some BrS patients, Endo ablation of the RVOT is effective as
well. The prime objective of this study was to examine the
electrophysiological basis for premature beats originating from the
endocardium (Endo) of the right ventricular outflow tract (RVOT) in
experimental models of Brugada syndrome (BrS). Methods:
Canine coronary-perfused cardiac preparations incorporating the RVOT
(n=15) were studied using standard microelectrode techniques.
Terfenadine, a sodium and calcium channel blocker, was used to
pharmacologically mimic the effects of the genetic defects associated
with BrS. Results: Under baseline conditions, a
prominent AP notch was recorded in Epi and in the deep intra-trabecular
structures of RVOT Endo, but not in the smooth Endo surface of the RVOT.
Terfenadine markedly accentuated the AP notch in the deep
intra-trabecular structures of RVOT Endo leading to the development of
closely-coupled phase 2 reentrant extrasystoles capable of triggering
polymorphic VT/V. Still, Epi RVOT region was more likely to develop
extrasystoles than Endo RVOT. VT/VF was recorded in 12/15 preparations.
Conclusions: Our findings suggest that the deep
intra-trabecular structures of RVOT Endo harbor the substrate for the
development of phase 2 reentrant extrasystoles capable of triggering
VT/VF. Our data may help to explain the effectiveness of Endo RVOT
ablation in some BrS patients.