Abstract
Sympathetic activity and spatial dispersion of repolarization (DOR) have been implicated as mechanisms that promote arrhythmia vulnerability; yet there are no direct measurements of the effects of autonomic nerve stimulation on DOR. Rabbit hearts were perfused in a Langendorff apparatus with full sympathetic and parasympathetic innervation and were optically mapped to measure action potential durations and DOR (apex-base) over the left ventricles. DOR was measured under sinus rhythm, during bilateral sympathetic nerve stimulation (SNS) and right and/or left vagus nerve stimulation and was compared with DOR during isoproterenol (100 nmol/L) or acetylcholine (1 micromol/L) infusion. In sinus rhythm, repolarization started at the apex and systematically progressed toward the base. SNS (10 to 15 Hz) increased DOR by 29% (from Deltaaction potential duration=17+/-0.7 to -22+/-1.6 ms, n=6) and reversed DOR as the direction of repolarization from apex-->base in sinus rhythm shifted to base-->apex in 5 to 15 seconds after SNS. DOR flipped back to its sinus rhythm DOR pattern 115+/-15 seconds after the interruption of SNS. During right or left vagus nerve stimulation, there was no change in the direction of DOR, but bilateral vagus nerve stimulation increased and reversed DOR to base-->apex direction. Infusion of isoproterenol or acetylcholine increased DOR but did not alter the direction of repolarization sequences. These findings demonstrate that bilateral autonomic activity (SNS or vagus nerve stimulation) cause reversible shifts of apex-base DOR and that the spatial heterogeneities of autonomic effects on the ventricles are most likely attributable to a greater innervation at the base than the apex of the heart.
Highlights
Sympathetic activity and spatial dispersion of repolarization (DOR) have been implicated as mechanisms that promote arrhythmia vulnerability; yet there are no direct measurements of the effects of autonomic nerve stimulation on DOR
Autonomic nerve stimulation was found to bring about a reversal of the direction of repolarization along the apex to base axis of the heart
The reversal of DOR had a rapid onset of Ͻ15 seconds after sympathetic nerve stimulation (SNS), and on stopping SNS, DOR reversed back to sinus rhythm DOR, with a latency of Ϸ2 minutes
Summary
Sympathetic activity and spatial dispersion of repolarization (DOR) have been implicated as mechanisms that promote arrhythmia vulnerability; yet there are no direct measurements of the effects of autonomic nerve stimulation on DOR. DOR was measured under sinus rhythm, during bilateral sympathetic nerve stimulation (SNS) and right and/or left vagus nerve stimulation and was compared with DOR during isoproterenol (100 nmol/L) or acetylcholine (1 mol/L) infusion. Infusion of isoproterenol or acetylcholine increased DOR but did not alter the direction of repolarization sequences These findings demonstrate that bilateral autonomic activity (SNS or vagus nerve stimulation) cause reversible shifts of apex– base DOR and that the spatial heterogeneities of autonomic effects on the ventricles are most likely attributable to a greater innervation at the base than the apex of the heart. In all animal models tested far, repolarization was shown to proceed from the apex to the base of the heart and to be independent of the activation sequence and to depend on intrinsic differences of action potential durations (APDs).[20] Transmural DOR was measured from isolated canine wedge preparations and found to differ significantly when paced on the endocardium (to mimic sinus rhythm) compared with epicardium.[21]. Enhanced DOR and dynamic properties of APDs such as the steepness of the APD restitution kinetics curve and APD (or T wave) alternans have been shown to promote arrhythmias.[25,26,27] Adrenergic agonists and/or autonomic imbalance
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