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 (Gd 3+ ) 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 H 2 O 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 H 2 O (mean±SEM) to induce AF. A dose-dependent decrease in AF vulnerability was observed after Gd 3+ 12.5, 25, and 50 μmol/L was added. AF threshold increased to 19.0±0.5 cm H 2 O with Gd 3+ 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 H 2 O at baseline but never during Gd 3+ . Atrial effective refractory period shortened progressively from 78±3 ms at 0.5 cm H 2 O to 52±3 ms at 20 cm H 2 O ( P <0.05). Gd 3+ 50 μmol/L had no significant effect on effective refractory period. Conclusions —Acute atrial stretch significantly enhances the vulnerability to AF. Gd 3+ 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.