(Circulation. 2000;101:2200.)
© 2000 American Heart Association, Inc.
Basic Science Reports |
Gadolinium Decreases Stretch-Induced Vulnerability to Atrial Fibrillation
From the Department of Pharmacology, Georgetown University (F.B., A.K., R.L.W., M.R.F.), and the Cardiology Division, Veterans Affairs Medical Center (M.R.F.), Washington, DC.
Correspondence to Michael R. Franz, MD, PhD, Cardiology Division, VAMC, 50 Irving St NW, Washington, DC 20422. E-mail mfranz{at}washington.va.gov
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.
Key Words: stretch • channels • fibrillation • gadolinium • mechanics
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