Cholestatic liver disease modulates susceptibility to ischemia/reperfusion-induced arrhythmia, but not necrosis and hemodynamic instability: the role of endogenous opioid peptides.
OBJECTIVE
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.
Hajrasouliha
Amir Reza
AR
Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, P.O. Box 13145-784, Tehran, Iran.
Tavakoli
Sina
S
Jabehdar-Maralani
Pejman
P
Ebrahimi
Farzad
F
Shafaroodi
Hamed
H
Mirkhani
Seyyed Hamid
SH
Amanpour
Saied
S
Dehpour
Ahmad Reza
AR
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000503:physiopathology*; D001794:Blood Pressure; D002780:Cholestasis, Intrahepatic / Q000473:pathology / Q000503:physiopathology*; D004562:Electrocardiography; D006339:Heart Rate; D006439:Hemodynamics; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009271:Naltrexone / Q000494:pharmacology; D009336:Necrosis; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000503:physiopathology*
D009271:Naltrexone; D019331:NG-Nitroarginine Methyl Ester