Sympathetic stimulation increases dispersion of repolarization in humans with myocardial infarction

Abstract

The sympathetic nervous system is thought to play a key role in genesis and maintenance of ventricular arrhythmias. The myocardial effect of sympathetic stimulation on myocardial repolarization in humans is poorly understood. The purpose of this study was to evaluate the effects of direct and reflex sympathetic stimulation on ventricular repolarization in patients with postinfarct cardiomyopathy (ICM). The effects of direct sympathetic stimulation were assessed using isoproterenol, while those of reflex sympathetic stimulation were assessed with nitroprusside infusion in ICM patients (n = 5). Five patients without cardiomyopathy were also studied. Local repolarization was measured from intracardiac electrograms that were used to calculate the activation recovery interval (ARI), a surrogate of action potential duration. Isoproterenol significantly increased heterogeneity in repolarization in patients with ICM; the decrease in ARI from baseline was 72.9 ± 9.1 ms in more viable regions, 64.5 ± 8.9 ms in the scar, and 54.9 ± 9.1 ms in border zones (P = 0.0002 and 0.014 comparing normal and scar to border zones, respectively). In response to nitroprusside, the ARI at the border zones decreased significantly more than either scar or surrounding viable myocardium, which showed an increase in ARI (P = 0.014 and 0.08 comparing normal tissue and scar to border zones, respectively). Furthermore, isoproterenol increased ARI dispersion by 70%, while nitroprusside increased ARI dispersion by 230% when ICM patients were compared to those with structurally normal hearts (P = 0.0015 and P < 0.001, respectively). In humans, both direct and reflex sympathetic stimulations increase regional differences in repolarization. The normal tissue surrounding the scar appears denervated. Dispersion of ARI in response to sympathetic stimulation is significantly increased in patients with ICM.

Focal myocardial infarction induces global remodeling of cardiac sympathetic innervation: neural remodeling in a spatial context

“…Changes in functional responses at remote regions may be mediated by changes to the ICN. The observations in the present study are consistent with findings in humans where the remote myocardium in humans showed attenuated ARI shortening in response to reflex sympathetic stimulation induced by nitroprusside (24).…”

“…To describe functional innervation patterns, the percent ARI shortening from baseline was computed from five to eight electrodes in each prespecified region during RSG, LSG, and BSG stimulation, as previously described (3,24).…”

“…These conditions may underlie the mechanisms by which arrhythmias are initiated when sympathetic tone is enhanced. autonomic nervous system; sympathetic nerves; cardiac innervation; neural remodeling REMODELING of the cardiac sympathetic nervous system after myocardial infarction (MI) has been linked to ventricular arrhythmias in animal models (29) and in humans (4,12,24). Modulation of cardiac sympathetic signaling is a major therapeutic strategy to prevent and treat ventricular arrhythmias (1,8,22).…”

Parasympathetic dysfunction and antiarrhythmic effect of vagal nerve stimulation following myocardial infarction

“…In addition, in infarcted hearts, bipolar voltage electroanatomic mapping was performed as described above, and location of each electrode overlying scar, border zone, or viable myocardium meticulously was noted. ARI was analyzed from unipolar electrograms of each electrode using iScaldyn (University of Utah, Salt Lake City, Utah, USA) (47,54,55). Briefly, activation time was defined from the origin to the minimum dV/dt of the activation wavefront of the unipolar electrogram, and recovery time was defined as the start of activation to the maximum dV/dt of repolarization wavefront.…”

Increase in QTC Dispersion Predicts Arrhythmic Events in Patients With Cardiac Resynchronization Therapy

“…Previous investigators have reported the role of repolarisation dispersion on the basis of ventricular malignant arrhythmias in heart failure patients [8][9][10]. Heterogenity of ventricular repolarisation facilitates transmural early after depolarization propagation and also can cause intramural conduction blocks that predispose to re-entrant tachyarrhythmias [11].…”