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

• Published in: Journal of hepatology Vol. 43; no. 3; pp. 491 - 498
• Main Authors: Hajrasouliha, Amir Reza, Tavakoli, Sina, Jabehdar-Maralani, Pejman, Ebrahimi, Farzad, Shafaroodi, Hamed, Mirkhani, Seyyed Hamid, Amanpour, Saied, Dehpour, Ahmad Reza
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier B.V 01.09.2005; Elsevier
• Subjects: Animals; Arrhythmia; Arrhythmias, Cardiac - etiology; Arrhythmias, Cardiac - physiopathology; Bile duct-ligation; Biological and medical sciences; Blood Pressure; Cardiac dysrhythmias; Cardiology. Vascular system; Cholestasis; Cholestasis, Intrahepatic - pathology; Cholestasis, Intrahepatic - physiopathology; Electrocardiography; Endogenous opioid peptides; Gastroenterology. Liver. Pancreas. Abdomen; Heart; Heart Rate; Hemodynamics; Ischemia/reperfusion; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Male; Medical sciences; Myocardial Infarction - pathology; Myocardial Infarction - physiopathology; Naltrexone - pharmacology; Necrosis; NG-Nitroarginine Methyl Ester - pharmacology; Nitric oxide (NO); Other diseases. Semiology; Rat; Rats; Rats, Sprague-Dawley; Reperfusion Injury - physiopathology; Endogenous opioid peptides; Arrhythmia; Rat; Ischemia/reperfusion; Cholestasis; Bile duct-ligation; Nitric oxide (NO); Necrosis; Biliary tract; Peptides; Ischemia reperfusion; Rodentia; Cardiovascular disease; Hepatic disease; Biliary tract disease; Vertebrata; Mammalia; Heart disease; Animal; Nitric oxide; Cholostasis; Digestive diseases; Instability; Hemodynamics
• ISSN: 0168-8278; 1600-0641
• DOI: 10.1016/j.jhep.2005.02.043

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. 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. 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). This study suggests that short-term cholestasis is associated with resistance against ischemia/reperfusion-induced arrhythmia, which depends on availability of endogenous opioids.