BACKGROUND Although the existence of myocardial mechanoelectrical feedback is well established, the mechanism of arrhythmia induction by ventricular dilatation or stretch remains insufficiently 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 wall stretch, we developed an isolated Langendorff-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-conducted 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 of varying pulse waveforms (three different amplitudes and five different rise velocities) applied randomly 250-350 times to each of eight hearts. Gradual LV volume 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). Logistic 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 stretch-activated arrhythmias on the velocity of stretch. In contrast, an increase in the basic ventricular volume had no effect on the probability of PVE occurrence during the volume pulses. The MAP recordings demonstrated spatial variability in the extent of local depolarizations and site of PVE origin; transient depolarizations occurred, and PVEs originated most often in the posterolateral region of the left ventricle. CONCLUSIONS Membrane depolarization is caused by both gradual and rapid ventricular stretch, but PVEs are more easily elicited by rapid stretch. Regions of greater myocardial compliance that experience greater relative stretch may act as "foci" for stretch-activated arrhythmias during dynamic ventricular loading. These whole-heart data corroborate the existence of stretch-activated membrane channels in ventricular myocardium and may help explain ventricular ectopy under conditions of differential ventricular loading, as in ventricular dyskinesia, or regional muscle traction, as in mitral valve prolapse syndrome.
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