title: QT interval dispersion and cardiac sympathovagal balance shift in rats with acute ethanol withdrawal.
abstract: BACKGROUND
  Dysregulation of autonomic nervous system function and impaired homogeneity of myocardial repolarization are 2 important mechanisms for the genesis of ventricular arrhythmias in nonalcoholic subjects. Our previous study suggested that acute ethanol withdrawal promoted the shift of cardiac sympathovagal balance toward sympathetic predominance and reduced the vagal tone, which were related to a higher incidence of ventricular arrhythmia and related death. However, the homogeneity of myocardial repolarization and its relation with the cardiac sympathovagal balance are unknown, especially in alcoholic subjects. The aim of the present study was to clarify these points.
  
  
  METHODS
  Male Wistar rats were treated with a continuous ethanol liquid diet for 49 days, and then subjected to 1-day withdrawal and 1-day withdrawal with 7-day carvedilol (can block the sympathetic nervous system completely via beta1, beta2, and alpha adrenergic receptors) pretreatment. The cardiac sympathovagal balance and homogeneity of myocardial repolarization were evaluated based on the heart rate variability (HRV) and QT interval dispersion (QTd: dynamic changes in QT interval duration).
  
  
  RESULTS
  The increase in QTd was observed only in rats at 1-day withdrawal, but not in nonalcoholic, continuous ethanol intake, and 1-day withdrawal with 7-day carvedilol pretreatment rats. At 1-day withdrawal, the low-frequency power/high-frequency power (LF/HF) ratio in HRV was elevated and correlated with the QTd. The increased QTd and elevated LF/HF ratio were normalized by the 7-day carvedilol pretreatment in rats at 1-day ethanol withdrawal.
  
  
  CONCLUSIONS
  In rats with an abrupt termination of the chronic continuous ethanol intake, the homogeneity of myocardial repolarization impaired and correlated with the cardiac sympathovagal balance. Carvedilol pretreatment is associated with a reduction in both the QTd and LF/HF ratio, raising the possibility that the cardiac sympathovagal balance shift may be responsible for the impaired homogeneity of myocardial repolarization, and that beta-blocker pretreatment may decrease the mortality risk during alcoholic withdrawal.
authors: Department of Legal Medicine, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors: Seiko
authors: S
authors: Shirafuji
authors: Jinyao
authors: J
authors: Liu
authors: Nanako
authors: N
authors: Okamura
authors: Kazuyuki
authors: K
authors: Hamada
authors: Tatsuya
authors: T
authors: Fujimiya
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D000428:Alcohol Drinking / Q000523:psychology; D000818:Animals; D002227:Carbazoles / Q000008:administration & dosage / Q000494:pharmacology; D000077261:Carvedilol; D002492:Central Nervous System Depressants / Q000009:adverse effects*; D004562:Electrocardiography / Q000187:drug effects*; D004573:Electrolytes / Q000097:blood; D000431:Ethanol / Q000009:adverse effects*; D006321:Heart / Q000187:drug effects* / Q000294:innervation*; D006439:Hemodynamics / Q000187:drug effects; D015918:Infusion Pumps, Implantable; D008133:Long QT Syndrome / Q000139:chemically induced* / Q000503:physiopathology; D008297:Male; D011412:Propanolamines / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012849:Sinoatrial Node / Q000187:drug effects / Q000502:physiology; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology*; D013564:Sympathetic Nervous System / Q000187:drug effects*; D013686:Telemetry; D014630:Vagus Nerve / Q000187:drug effects*
chemical_list: D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D002492:Central Nervous System Depressants; D004573:Electrolytes; D011412:Propanolamines; D000077261:Carvedilol; D000431:Ethanol