Gadolinium decreases stretch-induced vulnerability to atrial fibrillation

Background-Atrial fibrillation (AF) is frequently associated with atrial di latation caused by pressure or volume overload. Stretch-activated channels (SACs) have been found in myocardial cells and may promote AI: in dilated a tl ia. To prove this hypothesis, we investigated the effect of the SAC bloc ker gadolinium (Gd3+) on AF propensity in the isolated rabbit heart during atrial stretch. Methods and Results-In 16 isolated Langendorff-perfused rabbit hearts, the interatrial septum was perforated to equalize biatrial pressures. Caval and pulmonary veins were occluded. Intra-atrial pressure (IAP) was increased i n steps of ? to 3 cm H2O by increasing the pulmonary outflow fluid column. Vulnerability to AF was evaluated by 15-second burst pacing at each IAP lev el, At baseline, IAP needed to be raised to 8.8+/-0.2 cm H2O (mean+/-SEM) t o induce AF, A dose-dependent decrease in AF vulnerability was observed aft er Gd3+ 12.5, 25, and 50 mu mol/L was added, AF threshold increased to 19.0 +/-0.5 cm H2O with Gd3+ 50 mu mol/L (P<0.001 versus baseline). Spontaneous runs of AF occurred in 5 hearts on a rise of IAP to 13.8+/-3.3 cm H2O at ba seline but never during Gd3+. Atrial effective refractory period shortened progressively from 78+/-3 ms at 0.5 cm H2O to 52+/-3 ms at 20 cm H2O (P<0.0 5). Gd3+ 50 mu mol/L had no significant effect on effective refractory peri od. Conclusions-Acute atrial stretch significantly enhances the vulnerability t o AF, Gd3+ reduces the stretch-induced vulnerability to AF in a dose-depend ent manner. Block of SAC might represent a novel antiarrhythmic approach to AF under conditions of elevated atrial pressure or volume.