Modulation of QT interval by cardiac sympathetic nerve sprouting and the mechanisms of ventricular arrhythmia in a canine model of sudden cardiac death

Shengmei Zhou, Ji Min Cao, Zach D. Tebb, Toshihiko Ohara, Hsun Lun A. Huang, Chikaya Omichi, Moon Hyoung Lee, Bruce H. Kenknight, Lan S. Chen, Michael C. Fishbein, Hrayr S. Karagueuzian, Peng Sheng Chen

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Abstract

Introduction: We previously reported that there is a high incidence of sudden cardiac death (SCD) in dogs with myocardial infarction (MI), complete AV block (CAVB), and nerve growth factor (NGF) infusion to the left stellate ganglion (LSG). Whether or not QT interval prolongation underlines the mechanism of SCD was unclear. Methods and Results: We analyzed QT intervals in three groups of dogs. All dogs had CAVB and MI. The LSG group (n = 9) and right stellate ganglion (RSG) group (n = 6) received NGF infusion via the osmotic pumps over a 5-week period to LSG and RSG, respectively. The control group (n = 6) received no NGF. The dogs either died suddenly or were sacrificed within 2 to 3 months after MI. Heart rhythm and QT and RR intervals were monitored using implantable cardioverter defibrillator ECG recordings. There was a time-dependent increase of QTc intervals in the LSG group and a time-dependent decrease of QTc intervals in the RSG group. At the end of NGF infusion, QTc intervals in the LSG group (408 ± 41 msec) were significantly longer than those in the control (350 ± 41 msec; P < 0.05) and RSG groups (294 ± 23 msec; P < 0.01). In the LSG group, 4 of 9 dogs died of SCD. There was no SCD in either the RSG or control group. Immunocytochemical staining showed NGF infusion to LSG and RSG resulted in left and right ventricular sympathetic nerve sprouting and hyperinnervation, respectively. Conclusion: NGF infusion to the LSG in dogs with MI and CAVB resulted in increased QT interval and incidence of ventricular tachycardia, ventricular fibrillation, and SCD, whereas NGF infusion to the RSG shortened QT interval and reduced the incidence of ventricular tachycardia. These findings indicate that QT interval prolongation is causally related to the occurrence of ventricular arrhythmia in dogs with nerve sprouting, MI, and CAVB.

Original languageEnglish (US)
Pages (from-to)1068-1073
Number of pages6
JournalJournal of cardiovascular electrophysiology
Volume12
Issue number9
DOIs
StatePublished - Jan 1 2001

Fingerprint

Stellate Ganglion
Sudden Cardiac Death
Canidae
Cardiac Arrhythmias
Nerve Growth Factor
Dogs
Atrioventricular Block
Myocardial Infarction
Ventricular Tachycardia
Incidence
Control Groups
Implantable Defibrillators
Ventricular Fibrillation

Keywords

  • Arrhythmia
  • Heart block
  • Myocardial infarction
  • Sudden death
  • Sympathetic nerve

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Modulation of QT interval by cardiac sympathetic nerve sprouting and the mechanisms of ventricular arrhythmia in a canine model of sudden cardiac death. / Zhou, Shengmei; Cao, Ji Min; Tebb, Zach D.; Ohara, Toshihiko; Huang, Hsun Lun A.; Omichi, Chikaya; Lee, Moon Hyoung; Kenknight, Bruce H.; Chen, Lan S.; Fishbein, Michael C.; Karagueuzian, Hrayr S.; Chen, Peng Sheng.

In: Journal of cardiovascular electrophysiology, Vol. 12, No. 9, 01.01.2001, p. 1068-1073.

Research output: Contribution to journalArticle

Zhou, Shengmei ; Cao, Ji Min ; Tebb, Zach D. ; Ohara, Toshihiko ; Huang, Hsun Lun A. ; Omichi, Chikaya ; Lee, Moon Hyoung ; Kenknight, Bruce H. ; Chen, Lan S. ; Fishbein, Michael C. ; Karagueuzian, Hrayr S. ; Chen, Peng Sheng. / Modulation of QT interval by cardiac sympathetic nerve sprouting and the mechanisms of ventricular arrhythmia in a canine model of sudden cardiac death. In: Journal of cardiovascular electrophysiology. 2001 ; Vol. 12, No. 9. pp. 1068-1073.
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T1 - Modulation of QT interval by cardiac sympathetic nerve sprouting and the mechanisms of ventricular arrhythmia in a canine model of sudden cardiac death

AU - Zhou, Shengmei

AU - Cao, Ji Min

AU - Tebb, Zach D.

AU - Ohara, Toshihiko

AU - Huang, Hsun Lun A.

AU - Omichi, Chikaya

AU - Lee, Moon Hyoung

AU - Kenknight, Bruce H.

AU - Chen, Lan S.

AU - Fishbein, Michael C.

AU - Karagueuzian, Hrayr S.

AU - Chen, Peng Sheng

PY - 2001/1/1

Y1 - 2001/1/1

N2 - Introduction: We previously reported that there is a high incidence of sudden cardiac death (SCD) in dogs with myocardial infarction (MI), complete AV block (CAVB), and nerve growth factor (NGF) infusion to the left stellate ganglion (LSG). Whether or not QT interval prolongation underlines the mechanism of SCD was unclear. Methods and Results: We analyzed QT intervals in three groups of dogs. All dogs had CAVB and MI. The LSG group (n = 9) and right stellate ganglion (RSG) group (n = 6) received NGF infusion via the osmotic pumps over a 5-week period to LSG and RSG, respectively. The control group (n = 6) received no NGF. The dogs either died suddenly or were sacrificed within 2 to 3 months after MI. Heart rhythm and QT and RR intervals were monitored using implantable cardioverter defibrillator ECG recordings. There was a time-dependent increase of QTc intervals in the LSG group and a time-dependent decrease of QTc intervals in the RSG group. At the end of NGF infusion, QTc intervals in the LSG group (408 ± 41 msec) were significantly longer than those in the control (350 ± 41 msec; P < 0.05) and RSG groups (294 ± 23 msec; P < 0.01). In the LSG group, 4 of 9 dogs died of SCD. There was no SCD in either the RSG or control group. Immunocytochemical staining showed NGF infusion to LSG and RSG resulted in left and right ventricular sympathetic nerve sprouting and hyperinnervation, respectively. Conclusion: NGF infusion to the LSG in dogs with MI and CAVB resulted in increased QT interval and incidence of ventricular tachycardia, ventricular fibrillation, and SCD, whereas NGF infusion to the RSG shortened QT interval and reduced the incidence of ventricular tachycardia. These findings indicate that QT interval prolongation is causally related to the occurrence of ventricular arrhythmia in dogs with nerve sprouting, MI, and CAVB.

AB - Introduction: We previously reported that there is a high incidence of sudden cardiac death (SCD) in dogs with myocardial infarction (MI), complete AV block (CAVB), and nerve growth factor (NGF) infusion to the left stellate ganglion (LSG). Whether or not QT interval prolongation underlines the mechanism of SCD was unclear. Methods and Results: We analyzed QT intervals in three groups of dogs. All dogs had CAVB and MI. The LSG group (n = 9) and right stellate ganglion (RSG) group (n = 6) received NGF infusion via the osmotic pumps over a 5-week period to LSG and RSG, respectively. The control group (n = 6) received no NGF. The dogs either died suddenly or were sacrificed within 2 to 3 months after MI. Heart rhythm and QT and RR intervals were monitored using implantable cardioverter defibrillator ECG recordings. There was a time-dependent increase of QTc intervals in the LSG group and a time-dependent decrease of QTc intervals in the RSG group. At the end of NGF infusion, QTc intervals in the LSG group (408 ± 41 msec) were significantly longer than those in the control (350 ± 41 msec; P < 0.05) and RSG groups (294 ± 23 msec; P < 0.01). In the LSG group, 4 of 9 dogs died of SCD. There was no SCD in either the RSG or control group. Immunocytochemical staining showed NGF infusion to LSG and RSG resulted in left and right ventricular sympathetic nerve sprouting and hyperinnervation, respectively. Conclusion: NGF infusion to the LSG in dogs with MI and CAVB resulted in increased QT interval and incidence of ventricular tachycardia, ventricular fibrillation, and SCD, whereas NGF infusion to the RSG shortened QT interval and reduced the incidence of ventricular tachycardia. These findings indicate that QT interval prolongation is causally related to the occurrence of ventricular arrhythmia in dogs with nerve sprouting, MI, and CAVB.

KW - Arrhythmia

KW - Heart block

KW - Myocardial infarction

KW - Sudden death

KW - Sympathetic nerve

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