What is the clinical evidence from this study?

Study design: Other. Population: Atrial fibrillation (n=16). Intervention: Gadolinium (Gd3+) vs. Baseline. Primary outcome: Intra-atrial pressure threshold to induce atrial fibrillation (cm H2O) (p=<0.001).

May 9, 2000

Gadolinium Decreases Stretch-Induced Vulnerability to Atrial Fibrillation

Q: What are the key findings of this study?

Gadolinium 50 micromol/L significantly increased the intra-atrial pressure threshold required to induce atrial fibrillation from 8.8 to 19.0 cm H2O (P<0.001).

Key Result

Gadolinium 50 micromol/L significantly increased the intra-atrial pressure threshold required to induce atrial fibrillation from 8.8 to 19.0 cm H2O (P<0.001).

Structured PICO

Does gadolinium reduce stretch-induced vulnerability to atrial fibrillation in isolated rabbit hearts?

Population

16 isolated Langendorff-perfused rabbit hearts

Intervention

Gadolinium (Gd3+) at doses of 12.5, 25, and 50 micromol/L

Comparator

Baseline (before adding Gd3+)

Outcome

Vulnerability to atrial fibrillation (AF threshold measured by intra-atrial pressure needed to induce AF via burst pacing)surrogate

Gadolinium, a stretch-activated channel blocker, dose-dependently reduces vulnerability to atrial fibrillation induced by acute atrial stretch in isolated rabbit hearts.

Main Result

Absolute Event Rate: 19% vs 8.8%

p-value: p=<0.001

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 micromol/L was added. AF threshold increased to 19.0+/-0.5 cm H(2)O with Gd(3+) 50 micromol/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 micromol/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.