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

Reduced susceptibility to epinephrine-induced arrhythmias in cirrhotic rats: The roles of nitric oxide and endogenous opioid peptides

“…Male Sprague-Dawley rats, weighing 200-250 g, were housed in groups of 3-4 in a room controlled at 22 ± 1°C and maintained in an alternating 12-h light/12-h dark cycles, and allowed free access to food and water. Bile duct ligation and shamoperation were performed as described previously [6,7], under general anesthesia induced by intraperitoneal (i.p.) injection of ketamine HCl (50 mg/kg; Gedoon Richter, Budapest, Hungary) and chlorpromazine HCl (10 mg/kg; Daroupakhsh, Tehran, Iran).…”

“…The following parameters were determined at baseline: (1) PR interval; (2) QT interval, the interval between the beginning of Q wave and the end of T wave, which in small rodents in contrast to human is not well-characterized and appears as a shoulder of the QRS complex [6] and (3) RR interval.…”

“…While classically tachycardia is considered as a component of hyperdynamic circulation observed in cirrhosis [4], CBDL is usually associated with reduced basal HR [17]. The mechanism of bradycardia in biliary cirrhosis [17], as well as acute cholestasis [6,7,[10][11][12], is not yet completely understood. However, it might be attributable to the presence of bile salts or other negative inotropic agents accumulated in the plasma following the biliary obstruction.…”

“…While QT prolongation is expected to increase the susceptibility to arrhythmias and sudden death in congenital or acquired conditions [5], there is no evidence that the incidence of ventricular arrhythmias and sudden death is increased in cirrhotic patients ( [4], for review). Interestingly, the vulnerability to ventricular arrhythmias is reduced in cholestatic rats, even though they present QT interval prolongation [6,7].…”

“…However, studies on short-term bile duct-ligated rats suggest that these compounds are also involved in the development of a protective state against epinephrine and ischemia/reperfusion-induced arrhythmias [6,7].…”