Gadolinium decreases stretch-induced vulnerability to atrial fibrillation

Abstract

Background - Atrial fibrillation (AF) is frequently associated with atrial dilatation caused by pressure or volume overload. Stretch-activated channels (SACs) have been found in myocardial cells and may promote AF in dilated atria. To prove this hypothesis, we investigated the effect of the SAC blocker 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 in steps of 2 to 3 cm H2O by increasing the pulmonary outflow fluid column. Vulnerability to AF was evaluated by 15- second burst pacing at each IAP level. At baseline, IAP needed to be raised to 8.8 ± 0.2 cm H2O (mean ± SEM) to induce AF. A dose-dependent decrease in AF vulnerability was observed after Gd3+ 12.5, 25, and 50 μmol/L was added. AF threshold increased to 19.0 ± 0.5 cm H2O with Gd3+ 50 μmol/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 baseline 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<0.05). Gd3+ 50 μmol/L had no significant effect on effective refractory period. Conclusions - Acute atrial stretch significantly enhances the vulnerability to AF. Gd3+ reduces the stretch-induced vulnerability to AF in a dose-dependent manner. Block of SAC might represent a novel antiarrhythmic approach to AF under conditions of elevated atrial pressure or volume.