Objective To investigate pharmacokinetics of propofol administered by target-controlled infusion (TCI) in patients with liver failure. Methods Nine ASA Ⅳ patients with liver failure aged 32-53 years,weighing 60-81 kg,who would undergo liver transplantation,were enrolled in this study,and nine ASA Ⅰ-Ⅱ patients aged 22-59 years,weighing 46-70 kg,who would undergo selective upper abdominal surgery,were as control group. In the two groups,propofol was administered for 60 min by TCI via Graseby 3500 infusion pump incorporated with Stelpump software,while the target plasma propofol concentration was set at 2.5 ?g/ml. Arterial blood samples were taken immediately before and at 2,5,10,20,30,40,50,60,62.5,65,70,75,80,85,90 min after the start of propofol infusion,and the plasma concentrations of propofol were measured by using gas chromatography-mass spectrometry. The data obtained were analyzed by DAS pharmacokinetic software. Results The central volume of distribution (Vc),apparent volume of distribution (Vp) and total clearance (CL) were significantly larger in liver transplantation group than those in control group (P

Objective To investigate the effects of ultrarapid opiate detoxification during general anesthesia on the plasma morphine concentration and brain ?-endorphin content in rats addicted to morphine. Methods Ninety male Wistar rats aged 12-15 weeks weighing 180-220 g were randomized into 6 groups: group I normal animal ( n = 5); group II morphine addiction ( n = 5); group III natural withdrawal ( n = 20); group IV general anesthesia ( n = 20); group V general anesthesia + naloxone ( n = 20) and group VI clonidine pretreatment ( n = 20). Morphine addiction was induced by subcutaneous injection of increasing doses of morphine sulphate for 5 days (5, 10, 20, 40 and 50 mg? kg-1 t.i.d. ? 5 days) . Morphine detoxification was started on the 6th day. General anesthesia was induced and maintained with ?-OH and midazolam i.m. supplemented with intermittent isoflurane inhalation to maintain loss of righting reflex. Spontaneous breathing was kept during general anesthesia. In group V naloxone 0.05, 0.1 and 0.2 mg was injected subcutaneously at 5, 30 and 60 min after loss of righting reflex. Successful detoxification was defined as no withdrawal symptoms after subcutaneous injection of naloxone 0.1 mg. In group VI clonidine 0.05 mg ? kg-1 was given i. v. 1 hour before induction of anesthesia. Blood samples and brain tissue were obtained before detoxification in group I (normal animal) and II (morphine addiction) while in the other 4 groups they were obtained immediately and 1,2,3 day after detoxification.Results The plasma morphine concentration was 224 ? 164 ng?ml-1 in group II (morphine addiction), significantly higher than in all the detoxification groups ( P V ) (P

Objective To investigate the effects of remifentanil on large-conductance Ca2+ -activated potassium channel (BKCa) in human mesenteric arterial smooth muscle cells (MASMCs) and the mechanism of the vasorelaxant effect of remifentanil. Methods Human MASMCs were obtained freshly by the method of enzymolysis. BKCa current (IBKCa) was recorded by the whole-cell patch clamp technique. The changes in IBKC. produced by different concentrations of remifentanil (1.2, 4.8, 19.4, 77.4 and 310.0 nmol/L) with the holding potential of + 80 mV were observed. BKCa activation rate was calculated. Results Remifentanil significantly increased IBKCa,moved Ⅰ-Ⅴ curve upward and had no effect on the threshold of activation for IBKCa . With the increase in the concentration of remifentanil, BKCa activation rate increased gradually (P ＜ 0.01), and it remained stable when the concentration reached 19.4 nmol/L. There was no significant difference in the peak time of IBKCa after different concentrations of remifentanil were given (P ＞ 0.05). Logarithmic curve was found to suit the relationship between the concentration of remifentanil and BKCa activation rate and the IC50 concentration was (118 ± 7) nmol/L. Conclusion Remifentanil results in vasorelaxation by activating BKCa in MASMCs in a concentration-dependent manner.

Objective To investigate the acute toxicity of intravenous isoflurane in Beagles.Methods Six healthy adult Beagles of both sexes aged 6-8 months weighing 6-8 kg were used in this study.Isoflurane injectio (120 mg/ml) in 30% hpid emulsion was injected intravenously. Femoral artery was cannulated for direct BP monitoring.ECG was continuously monitored.The maximal tolerance dose (MTD) and approximate lethal dose (ALD) were determined by up-and-down technique. The initial dose was 3.0 ml/kg. The dose was decreased/increased by 0.3 ml/kg if the previous animal died/survived.The survived dogs were observed for 2 weeks.Autopsy and histopathological examination were performed on all dead Beagles.Results The ALD and MTD of intravenous isoflurane were 252 and 216 mg/kg. Autopsy and histopathological examination did not show any abnormality.Conclusion Cardiopulmonary depression is the main manifestation of the acute toxicity of intravenous isoflurane in Beagles.

In left heart disease, pulmonary artery pressure would increase due to the elevated left atrial pressure. This type of pulmonary hypertension (PH) is belonged to type Ⅱ as a passive PH (pPH) in its classification. The essential cause of pPH is excessive blood volume. Recently, we have identified another type of pPH, which is induced by vasopressors. Vasopressor-induced pPH shares similar pathophysiological manifestations with left heart disease-induced pPH. pPH would, therefore, be aggressive if vasopressors were applied in patients with left heart disease, which may be common after cardiac surgery, because heart undergoing surgical trauma may require support of vasopressors. Unfortunately, pPH after cardiac surgery is often ignored because of the difficulty in diagnosis. To improve the understanding of pPH and its effect on outcomes, here we highlight the mechanisms of interaction between vasopressor-induced and left heart failure-induced pPH, and provide insights into its therapeutic options.