Stretch-Activated Arrhythmias

Background. Although the existence of myocardial mechanoelectrical feedback is well established, the mechanism of arrhythmia induction by ventricular dilatation or stretch remains insuffliciently defined. In particular, controversy exists when comparing the arrhythmogenic potential of chronic versus acute myocardial stretch. Also, assessment of cellular electrophysiological effects of myocardial stretch has been incomplete. Methods and Results. To evaluate the electrophysiological and arrhythmogenic effects of slow versus rapid ventricular wail stretch, we developed an isolated Langendorf-perfused rabbit heart model in which left ventricular (LV) volume can be changed by a computer-controlled servopump. Cellular electrophysiological effects and premature ventricular excitations (PVEs) and their origin produced by the volume increases were assessed by a multiple-site monophasic action potential (MAP) recording system and by volume-onducted ECGs obtained by immersing the entire preparation in a saline-filled tank. Volume was increased either gradually with slow volume ramps (0.1 ml/sec) or suddenly by volume pulses ofvarying pulse wavefonns (three different amplitudes and five different rise velocities) applied randomly 250-350 times to each of eight hearts. Gradual LVvolume loading caused gradual decreases in MAP resting and action potential amplitude, whereas rapid, transient volume pulses caused transient depolarizations. Despite similar membrane potential effects of stretch, gradual volume increases rarely (11%) produced PVEs, even with large volume loads, whereas rapid volume pulses of moderate amplitudes regularly triggered PVEs (45-100% of interventions). L.ogistic regression analysis showed that the probability of PVE occurrence increased independently with both the amplitude and the velocity of the volume increase, with the greatest sensitivity to stretch velocity exhibited at low and intermediate pulse amplitudes. Faster volume pulse rise velocities triggered PVEs at a lower instantaneous pulse amplitude than lower rise velocities, further corroborating the dependence of stretchactivated arrhythmias on the velocity of stretch. In contrast, an increase in the basic ventricular volume had