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

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.

• Authors: Amir Reza Hajrasouliha, Sina Tavakoli, Pejman Jabehdar-Maralani, Farzad Ebrahimi, Hamed Shafaroodi, Seyyed Hamid Mirkhani, Saied Amanpour, Ahmad Reza Dehpour
• Journal: Journal of hepatology (J Hepatol) Vol. 43 Issue 3 Pg. 491-8 (Sep 2005) ISSN: 0168-8278 [Print] Netherlands
• PMID: 16023251 (Publication Type: Journal Article)

Chemical References

• Naltrexone
• NG-Nitroarginine Methyl Ester

Topics

• Animals
• Arrhythmias, Cardiac (etiology, physiopathology)
• Blood Pressure
• Cholestasis, Intrahepatic (pathology, physiopathology)
• Electrocardiography
• Heart Rate
• Hemodynamics
• Male
• Myocardial Infarction (pathology, physiopathology)
• NG-Nitroarginine Methyl Ester (pharmacology)
• Naltrexone (pharmacology)
• Necrosis
• Rats
• Rats, Sprague-Dawley
• Reperfusion Injury (physiopathology)