Cholestatic liver disease modulates susceptibility to ischemia/reperfusion- induced arrhythmia, but not necrosis and hemodynamic instability: The role of endogenous opioid peptides

Amir Reza Hajrasouliha, Sina Tavakoli, Pejman Jabehdar-Maralani, Farzad Ebrahimi, Hamed Shafaroodi, Seyyed Hamid Mirkhani, Saied Amanpour, Ahmad Reza Dehpour

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Background/Aims: Acute cholestasis is associated with cardiovascular complications, which mainly manifest during stressful conditions. The goal of this study is to evaluate susceptibility of 7-day bile duct-ligated rats to ischemia/reperfusion-induced injury. Methods: Sham-operated and cholestatic rats, treated with daily normal saline, L-NAME (a non-selective NO synthase inhibitor) naltrexone, or both L-NAME and naltrexone were subjected to 30 min of ischemia followed by 2 h of reperfusion. Results: Cholestatic rats demonstrated significant bradycardia, hypotension (P<0.01), and QT prolongation (P<0.001). The incidence of premature ventricular contractions (P<0.01), incidence and duration of ventricular tachycardia (P<0.05), but not ventricular fibrillation, were significantly lower in cholestatic rats. There was no significant difference in hemodynamic instability and infarct size between the groups. L-NAME corrected QT prolongation in cholestatic rats (P<0.05), with no effect on heart rate, blood pressure and arrhythmia. Naltrexone restored normal heart rate (P<0.05), blood pressure (P<0.05) and susceptibility to arrhythmia (P<0.05) in cholestatic animals, with no significant effect on QT interval. L-NAME and naltrexone co-administration corrected bradycardia (P<0.05), hypotension (P<0.05), QT prolongation (P<0.05) and abolished resistance of cholestatic rats against arrhythmia (P<0.05). Conclusions: This study suggests that short-term cholestasis is associated with resistance against ischemia/reperfusion-induced arrhythmia, which depends on availability of endogenous opioids.

Original languageEnglish (US)
Pages (from-to)491-498
Number of pages8
JournalJournal of Hepatology
Volume43
Issue number3
DOIs
StatePublished - Sep 1 2005
Externally publishedYes

Keywords

  • Arrhythmia
  • Bile duct-ligation
  • Cholestasis
  • Endogenous opioid peptides
  • Ischemia/reperfusion
  • Necrosis
  • Nitric oxide (NO)
  • Rat

ASJC Scopus subject areas

  • Hepatology

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