Stretch-induced depolarizations as a trigger of arrhythmias in isolated canine left ventricles

Transient diastolic stretch of the left ventricle predictably elicits arrhythmias. To investigate the mechanism of such stretch-induced arrhythmias, monophasic action potentials were recorded from six blood-perfused isolated canine left ventricles with an epicardial contact electrode. Stretch-induced arrhythmias were elicited using a computerized servo-pump system that increased left ventricular volume for 250 ms during early diastole. Depolarizations that coincided with the onset of stretch were observed that always preceded the stretch-induced arrhythmia. As stretch volume (delta V) increased from 10 to 30 ml, the amplitude of the stretch-induced depolarization increased progressively and the probability of eliciting an arrhythmia rose from 30 to 94%. To exclude motion artifact, additional recordings were made after the heart was depolarized by increasing the perfusate K+ concentration to 154 mM (K arrest). After K arrest, the stretch-induced depolarizations were reduced by 95% or more (P less than 0.05) at all stretch volumes. Thus the change in monophasic action potential signal during transient diastolic stretch reflects actual depolarization of the myocardium with negligible motion artifact. When the stretch-activated channel blocker, Gd3+ (10 microM), was administered, which produces potent inhibition of stretch-induced arrhythmias in our model, the stretch-induced depolarizations were substantially reduced in magnitude. Our results show that as diastolic stretch increases, stretch-induced depolarizations become larger and reach threshold potential more often; consequently, the probability of eliciting a stretch-induced arrhythmia increases. This mechanism of arrhythmogenesis may be particularly important in patients with regionally or globally dilated left ventricles.