Abstract 19293: Functional and Molecular Arrhythmogenic Substrates of Atrial Fibrillation Drivers (Reentrant Rotors) in Explanted Human Hearts
Introduction: The underlying mechanisms for arrhythmogenic sources of human atrial fibrillation (AF drivers) remain unclear. Adenosine (Ado) is a clinical drug used to induce AF. We aim to characterize the functional and molecular substrates responsible for AF drivers during Ado-induced AF in explanted human hearts.
Methods: Coronary perfused whole human atria (n=18), isolated from explanted human hearts with various cardiac diseases, were optically mapped from the epi- and/or endocardium simultaneously using two high-resolution CMOS cameras (3x3cm2-10x10cm2 field of view). Atrial activation patterns and action potential durations (APD) were analyzed during baseline and Ado perfusion (10-100μM). AF induction was attempted with burst pacing. Atrial tissues of interest were collected before and after mapping to study structure and protein expression by analyzing histology, immunostaining and western blotting (WB).
Results: Sustained AF was induced in 6/18 human atria by using burst pacing during Ado perfusion. In all 6 hearts, one or two sustained reentrant rotors were indentified in the pectinate muscle network of the lateral right atrial free wall (RAFW). The AF drivers were preferentially localized in specific regions (~1x1 cm2) of the lateral RAFW with the shortest APD compared to other atrial tissue during Ado perfusion (Figure). Hearts in which AF was induced exhibited more pronounced APD80% shortening in the RAFW (88 ± 29ms vs. 36 ± 9ms, at 2Hz pacing, p=0.003) than hearts without AF. Immunostaining and WB showed 2-3 fold higher adenosine A1 receptor (A1R) and GIRK4 expression in the lateral RAFW arrhythmogenic regions vs atrial tissue outside the preferential AF driver areas.
Conclusions: The higher expression of A1R and GIRK4 in the human lateral RAFW may be responsible for pronounced shortening of APD and AF inducuibility by adenosine. It is also directly correlated with the localization of the sustained AF reentrant rotors in human hearts.
Author Disclosures: N. Li: None. B.J. Hansen: None. J. Zhao: None. L. Jayne: None. B. Moore: None. T.A. Csepe: None. R.S. Higgins: None. A. Kilic: None. R. Weiss: None. P.J. Mohler: None. P.M. Janssen: None. B.J. Biesiadecki: None. J.D. Hummel: Research Grant; Modest; Biosense Webster. Consultant/Advisory Board; Modest; Medtronic. V.V. Fedorov: None.
- © 2014 by American Heart Association, Inc.