Gadolinium decreases stretch-induced vulnerability to atrial fibrillation

Article

关键词: CONTRACTION-EXCITATION FEEDBACK;    ISOLATED VENTRICULAR MYOCYTES;    ACTIVATED ION CHANNELS;    CULTURED CHICK HEART;    INDUCED ARRHYTHMIAS;    REFRACTORY PERIOD;    GUINEA-PIG;    RAT-HEART;    HUMANS;    TEMPERATURE;   

DOI  :  10.1161/01.CIR.101.18.2200

来源: SCIE

【 摘 要 】

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 AI: in dilated atl ia. 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 ? 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 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 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 mu mol/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.

【 授权许可】

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