The vitamin E derivative, EPC-K1, suppresses inflammation during hepatic ischemia-reperfusion injury and exerts hepatoprotective effects in rats.

BACKGROUND: An important component of postoperative management includes alleviation of hepatic ischemia-reperfusion (I/R) injury, which commonly results from liver surgery. EPC-K1 is a hydroxyl radical scavenger reported to have mitigating effects on I/R injury in many organs. This study evaluates the effects of EPC-K1 on hepatic I/R injury. MATERIALS AND METHODS: Rats were injected subcutaneously with either EPC-K1 (100 mg/kg) or saline. The hepatic artery and left branch of the portal vein were clamped for 45 min under general anesthesia. Indicators of liver function, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH), and of liver tissue damage were evaluated after 6h and 24h of reperfusion. Serum levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and high-mobility group box 1 (HMGB1) protein were measured, and apoptosis was quantified via caspase 3/7 activity and TUNEL assay. RESULTS: AST, ALT, and LDH levels increased significantly as a result of hepatic I/R injury, but were attenuated by EPC-K1 administration. Histologic findings revealed that normal structure of the hepatic parenchyma was maintained in rats pretreated with EPC-K1. TNF-α, IL-6, and HMGB1 levels rose significantly after reperfusion, together with activation of the inflammatory response. However, EPC-K1 administration suppressed levels of inflammatory markers and attenuated the inflammatory response. Moreover, EPC-K1 administration prevented apoptosis as determined by inhibition of caspase 3/7 activity and a decrease in apoptotic cells. CONCLUSIONS: Results demonstrate that EPC-K1 inhibits the inflammatory response and suppresses apoptosis during hepatic I/R injury. This suggests that EPC-K1 has hepatoprotective effects, and may be a valuable and novel therapeutic agent in the clinical setting.

Pharmacokinetics of propofol in elderly coronary artery bypass graft patients under total intravenous anesthesia.

The present paper investigates the pharmacokinetics of propofol in the plasma of two elderly patients operated on under total intravenous anesthesia using propofol. A 78-year-old (patient A) and a 76-year-old (patient B), both Japanese men with unstable angina pectoris, were operated on for coronary artery bypass grafts. For the induction of anesthesia, 1.5 mg/kg propofol was administered as a single bolus infusion, and anesthesia was maintained using the step-down infusion regimens of propofol. Propofol concentration in the plasma was measured by HPLC with a fluorescence detector. The simulation curves, following the two-compartment model, fitted well to the profiles of the individual data of propofol concentrations in the plasma. When 4 mg/kg/h of propofol was administered to both patients while maintaining anesthesia, propofol concentrations in the plasma were maintained at over 1.0 microg/ml. In patient A, the propofol concentration in the plasma was 140 ng/ml at 6 h after the end of the infusion. In patient B, the propofol concentrations in the plasma were 73 ng/ml at 6 h and 35 ng/ml at 12 h after the end of the infusion. The apparent distribution volumes of patients A and B were 1.43 and 1.62 l/kg, respectively. The half-lives of propofol in the plasma of patients A and B were estimated to be 13.3 and 17.4 min as the a phase, and 10.1 and 10.5 h as the beta phase, respectively. In elderly patients with cardiac surgery, the maintenance concentrations of propofol in the plasma were enough to maintain a concentration of 1.0 microg/ml, and the half-life may be longer than previously reported values in adult patients.