Search

Background/Aims: The clinical relevance of QT prolongation, the most widely recognized cardiac electrophysiological abnormality of cirrhosis, is still undefined. The aim of this study is to examine the susceptibility of chronic (4-week) bile duct-ligated rats to epinephrine-induced arrhythmias. The roles of nitric oxide and endogenous opioids were also evaluated. Methods: Sham-operated and cirrhotic rats were treated with daily subcutaneous administrations of normal saline (1ml/kg/day), l-NAME (a non-selective nitric oxide synthase inhibitor, 3mg/kg/day), and naltrexone (20mg/kg/day) during the fourth week after operation. In order to evaluate the effects of acute nitric oxide synthesis inhibition, additional groups of animals were treated by acute intraperitoneal l-NAME injections (3mg/kg). Arrhythmias were induced by intravenous injections of 10μg/kg epinephrine. Results: Despite QT prolongation (P <0.001), epinephrine induced fewer arrhythmias in cirrhotic rats compared to sham-operated animals (P <0.05). Chronic, but not acute, l-NAME administration corrected the QT prolongation in cirrhotic rats (P <0.001), and restored the susceptibility of cirrhotic rats to arrhythmias (P <0.05). Naltrexone injection without a significant effect on epinephrine-induced arrhythmias corrected QT interval in cirrhotic rats (P <0.001). Conclusions: This study shows that despite QT prolongation, cirrhotic animals are resistant against epinephrine-induced arrhythmias. This resistance is mediated by chronic nitric oxide overproduction. [Copyright &y& Elsevier]

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 30min of ischemia followed by 2h of reperfusion. Results: Cholestatic rats demonstrated significant bradycardia, hypotension (P&#60;0.01), and QT prolongation (P&#60;0.001). The incidence of premature ventricular contractions (P&#60;0.01), incidence and duration of ventricular tachycardia (P&#60;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&#60;0.05), with no effect on heart rate, blood pressure and arrhythmia. Naltrexone restored normal heart rate (P&#60;0.05), blood pressure (P&#60;0.05) and susceptibility to arrhythmia (P&#60;0.05) in cholestatic animals, with no significant effect on QT interval. L-NAME and naltrexone co-administration corrected bradycardia (P&#60;0.05), hypotension (P&#60;0.05), QT prolongation (P&#60;0.05) and abolished resistance of cholestatic rats against arrhythmia (P&#60;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. [Copyright &y& Elsevier]