Dose-Dependent Inhibition of Stretch-Induced Arrhythmias by Gadolinium in Isolated Canine Ventricles: Evidence for a Unique Mode of Antiarrhythmic Action

Transient diastolic dilatation of the isolated canine left ventricle predictably elicits arrhythmias. To test the hypothesis that such arrhythmias may be mediated by sarcolemmal stretch-activated channels, we attempted to inhibit stretch-induced arrhythmias with gadolinium (Gd), a potent stretch-activated channel blocker. In experiments with six isolated canine hearts, left ventricular volume was increased for 50 msec during early diastole and then returned to initial volume by a computerized servopump. The stretch volume was adjusted to yield a probability of eliciting a stretch-induced arrhythmia of 95±2% before treatment with Gd. When Gd (1–10 μM) was administered, dose-dependent suppression of stretch-induced arrhythmias was observed. The probability of a stretch-induced arrhythmia was reduced to 13×10% (p