title: 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 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.
  
  
  RESULTS
  In Yorkshire pigs (n=13), a sternotomy was performed and the heart and bilateral stellate ganglia 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, DOR, defined as variance in repolarization time, and Tp-e were assessed before and after left, right, and bilateral stellate ganglia stimulation and norepinephrine infusion. LV endocardial and epicardial activation recovery intervals significantly decreased, and LV endocardial and epicardial DOR increased during sympathetic nerve stimulation. There were no LV epicardial versus endocardial differences in activation recovery interval during sympathetic stimulation, and regional endocardial activation recovery interval 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, norepinephrine 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 norepinephrine did not affect DOR or Tp-e.
authors.affiliation: From the UCLA Cardiac Arrhythmia Center (D.Y., R.W.C., P.S.R., O.A.A., K.N., E.L.S., K.S., M.V.), UCLA Neurocardiology Center of Excellence (D.Y., R.W.C., K.Y., P.S.R., O.A.A., K.N., E.L.S., A.M., K.S., M.V.), and Department of Cardiac Anesthesia (K.Y., A.M.), University of California, Los Angeles.
authors.forename: Daigo
authors.initials: D
authors.lastname: Yagishita
authors.affiliation: From the UCLA Cardiac Arrhythmia Center (D.Y., R.W.C., P.S.R., O.A.A., K.N., E.L.S., K.S., M.V.), UCLA Neurocardiology Center of Excellence (D.Y., R.W.C., K.Y., P.S.R., O.A.A., K.N., E.L.S., A.M., K.S., M.V.), and Department of Cardiac Anesthesia (K.Y., A.M.), University of California, Los Angeles.
authors.forename: Ray W
authors.initials: RW
authors.lastname: Chui
authors.affiliation: From the UCLA Cardiac Arrhythmia Center (D.Y., R.W.C., P.S.R., O.A.A., K.N., E.L.S., K.S., M.V.), UCLA Neurocardiology Center of Excellence (D.Y., R.W.C., K.Y., P.S.R., O.A.A., K.N., E.L.S., A.M., K.S., M.V.), and Department of Cardiac Anesthesia (K.Y., A.M.), University of California, Los Angeles.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Yamakawa
authors.affiliation: From the UCLA Cardiac Arrhythmia Center (D.Y., R.W.C., P.S.R., O.A.A., K.N., E.L.S., K.S., M.V.), UCLA Neurocardiology Center of Excellence (D.Y., R.W.C., K.Y., P.S.R., O.A.A., K.N., E.L.S., A.M., K.S., M.V.), and Department of Cardiac Anesthesia (K.Y., A.M.), University of California, Los Angeles.
authors.forename: Pradeep S
authors.initials: PS
authors.lastname: Rajendran
authors.affiliation: From the UCLA Cardiac Arrhythmia Center (D.Y., R.W.C., P.S.R., O.A.A., K.N., E.L.S., K.S., M.V.), UCLA Neurocardiology Center of Excellence (D.Y., R.W.C., K.Y., P.S.R., O.A.A., K.N., E.L.S., A.M., K.S., M.V.), and Department of Cardiac Anesthesia (K.Y., A.M.), University of California, Los Angeles.
authors.forename: Olujimi A
authors.initials: OA
authors.lastname: Ajijola
authors.affiliation: From the UCLA Cardiac Arrhythmia Center (D.Y., R.W.C., P.S.R., O.A.A., K.N., E.L.S., K.S., M.V.), UCLA Neurocardiology Center of Excellence (D.Y., R.W.C., K.Y., P.S.R., O.A.A., K.N., E.L.S., A.M., K.S., M.V.), and Department of Cardiac Anesthesia (K.Y., A.M.), University of California, Los Angeles.
authors.forename: Keijiro
authors.initials: K
authors.lastname: Nakamura
authors.affiliation: From the UCLA Cardiac Arrhythmia Center (D.Y., R.W.C., P.S.R., O.A.A., K.N., E.L.S., K.S., M.V.), UCLA Neurocardiology Center of Excellence (D.Y., R.W.C., K.Y., P.S.R., O.A.A., K.N., E.L.S., A.M., K.S., M.V.), and Department of Cardiac Anesthesia (K.Y., A.M.), University of California, Los Angeles.
authors.forename: Eileen L
authors.initials: EL
authors.lastname: So
authors.affiliation: From the UCLA Cardiac Arrhythmia Center (D.Y., R.W.C., P.S.R., O.A.A., K.N., E.L.S., K.S., M.V.), UCLA Neurocardiology Center of Excellence (D.Y., R.W.C., K.Y., P.S.R., O.A.A., K.N., E.L.S., A.M., K.S., M.V.), and Department of Cardiac Anesthesia (K.Y., A.M.), University of California, Los Angeles.
authors.forename: Aman
authors.initials: A
authors.lastname: Mahajan
authors.affiliation: From the UCLA Cardiac Arrhythmia Center (D.Y., R.W.C., P.S.R., O.A.A., K.N., E.L.S., K.S., M.V.), UCLA Neurocardiology Center of Excellence (D.Y., R.W.C., K.Y., P.S.R., O.A.A., K.N., E.L.S., A.M., K.S., M.V.), and Department of Cardiac Anesthesia (K.Y., A.M.), University of California, Los Angeles.
authors.forename: Kalyanam
authors.initials: K
authors.lastname: Shivkumar
authors.affiliation: From the UCLA Cardiac Arrhythmia Center (D.Y., R.W.C., P.S.R., O.A.A., K.N., E.L.S., K.S., M.V.), UCLA Neurocardiology Center of Excellence (D.Y., R.W.C., K.Y., P.S.R., O.A.A., K.N., E.L.S., A.M., K.S., M.V.), and Department of Cardiac Anesthesia (K.Y., A.M.), University of California, Los Angeles. mvaseghi@mednet.ucla.edu.
authors.forename: Marmar
authors.initials: M
authors.lastname: Vaseghi
mesh_terms: D000200:Action Potentials; D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage*; D000818:Animals; D016757:Death, Sudden, Cardiac / Q000209:etiology*; D004195:Disease Models, Animal; D004558:Electric Stimulation; D004699:Endocardium / Q000294:innervation*; D005260:Female; D006352:Heart Ventricles / Q000294:innervation*; D006439:Hemodynamics; D007262:Infusions, Intravenous; D009638:Norepinephrine / Q000008:administration & dosage*; D010496:Pericardium / Q000294:innervation*; D013233:Stellate Ganglion / Q000378:metabolism* / Q000503:physiopathology*; D013997:Time Factors
chemical_list: D000316:Adrenergic alpha-Agonists; D009638:Norepinephrine
keywords: ECG; T wave; action potential; autonomic nervous system; dispersion; sympathetic