Sympathetic Nerve Stimulation, Not Circulating Norepinephrine, Modulates T-Peak to T-End Interval by Increasing Global Dispersion of Repolarization

Abstract

Background T-peak to T-end interval (Tp-e) is an independent marker of sudden cardiac death. Modulation of Tp-e by sympathetic nerve activation and circulating norepinephrine (NE) is not well understood. The purpose of this study was to characterize endocardial and epicardial dispersion of repolarization (DOR) and its effects on Tp-e with sympathetic activation. Methods and Results In Yorkshire pigs (n=13), a sternotomy was performed and the heart and bilateral stellate ganglia (SG) were exposed. A 56-electrode sock and 64-electrode basket catheter were placed around the epicardium and in the left ventricle (LV), respectively. Activation recovery interval (ARI), dispersion of repolarization (DOR), defined as variance in repolarization time, and Tp-e were assessed before and after left, right, and bilateral SG stimulation and NE infusion. LV endocardial and epicardial ARIs significantly decreased, and LV endocardial and epicardial DOR increased during sympathetic nerve stimulation. There were no LV epicardial vs. endocardial differences in ARI during sympathetic stimulation and regional endocardial ARI patterns were similar to the epicardium. Tp-e prolonged during left (from 40.4±2.2 ms to 92.4±12.4 ms; P<0.01), right (from 47.7±2.6 ms to 80.7±11.5 ms; P<0.01), and bilateral (from 47.5±2.8 ms to 78.1±9.8 ms; P<0.01) stellate stimulation and strongly correlated with whole heart DOR during stimulation (P<0.001, R=0.86). Of note, NE infusion did not increase DOR or Tp-e. Conclusions Regional patterns of LV endocardial sympathetic innervation are similar to that of LV epicardium. Tp-e correlated with whole heart DOR during sympathetic nerve activation. Circulating NE did not affect DOR or Tp-e.

The nervous heart

“…These authors further observed that application of the β-AR agonist isoproterenol also increased the DOR, but the spatial distribution of APD shortening was completely different, suggesting that the dramatic changes in repolarization observed with sympathetic nerve stimulation are due to heterogeneous nerve distribution. Similar results have been obtained in the porcine ventricles in which dramatically different spatial patterns of activation-recovery intervals (ARIs, surrogate measure for APD) and repolarization were observed in response to sympathetic nerve stimulation compared to circulating NE (Ajijola et al, 2013a; Yagishita et al, 2015). Furthermore, these investigators also found that nerve stimulation, but not NE infusion, increased the T-peak to T-end interval, which is an independent marker of sudden cardiac death (Yagishita et al, 2015).…”

Efficacy of Stellate Ganglion Blockade in Managing Electrical Storm

“…SGB may also be particularly useful for attenuating burst discharge activity in left stellate ganglion, which has been shown to precede most VT and sudden cardiac death in a canine model of ischemic cardiomyopathy (42–43). Sympathoexcitation increases repolarization heterogeneity (44–46), increases risk of delayed after depolarizations (47,48), and increases arrhythmia inducibility (49). It also modulates peri-infarct tissues harboring circuits capable of facilitating MMVT (50).…”

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

“…The right and left stellate ganglia were isolated behind the parietal pleura. Bipolar needle electrodes attached to a photoelectric isolation unit and Grass stimulator (Grass Technologies, S88 and PSIU6) were used for stimulation (54). The current required for a 10% increase in heart rate or systolic blood pressure at 4 Hz and 4 ms was defined as threshold.…”

“…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.…”