PURPOSE: Sedatives must be carefully titrated for patients with obstructive sleep apnea-hypopnea syndrome (OSAHS) as oversedation may lead to disastrous respiratory outcomes. This study aimed to investigate the relations between the effect-site concentration (Ce) of propofol and sedation and airway obstruction levels in patients with OSAHS. MATERIALS AND METHODS: In 25 patients with OSAHS, sedation was induced by 2% propofol using target-controlled infusion. Sedation and airway obstruction levels were assessed using the Observer's Assessment of Alertness/Sedation Scale and a four-category scale, respectively. The relationships between propofol Ce and sedation and airway obstruction were evaluated using a sigmoid Emax model. Pharmacodynamic modeling incorporating covariates was performed using the Nonlinear Mixed Effects Modeling VII software. RESULTS: Increased propofol Ce correlated with the depth of sedation and the severity of airway obstruction. Predicted Ce50(m) (Ce associated with 50% probability of an effect> or =m) for sedation scores (m> or =2, 3, 4, and 5) and airway-obstruction scores (m> or =2, 3, and 4) were 1.61, 1.78, 1.91, and 2.17 microg/mL and 1.53, 1.64, and 2.09 microg/mL, respectively. Including the apnea-hypopnea index (AHI) as a covariate in the analysis of Ce50(4) for airway obstruction significantly improved the performance of the basic model (p<0.05). CONCLUSION: The probability of each sedation and airway obstruction score was properly described using a sigmoid Emax model with a narrow therapeutic range of propofol Ce in OSAHS patients. Patients with high AHI values need close monitoring to ensure that airway patency is maintained during propofol sedation.
Adult ; Aged ; Airway Obstruction/*drug therapy ; Anesthesia ; Anesthetics, Intravenous/blood/pharmacokinetics/*pharmacology ; Female ; Humans ; Hypnotics and Sedatives/*pharmacology/therapeutic use ; Male ; Middle Aged ; Probability ; Propofol/*pharmacology/therapeutic use ; Sleep Apnea, Obstructive/physiopathology

BACKGROUNDSurgical stress causes a helper T-cell type 2 (Th2)-dominant status and disturbs the Th1/Th2 cytokine balance. Anesthesia can suppress the stress response to surgery, therefore it may inhibit the imbalance in the Th1/Th2 ratio. In this study, we assessed if propofol anesthesia and sevoflurane anesthesia influence the Th1/Th2 cytokine balance, and which anesthesia method better attenuates this ratio.

METHODSTwenty-eight patients with an American Society of Anesthesiologists (ASA) physical status of I undergoing laparoscopic cholecystectomy were selected. They were randomly allocated into two groups of 14. Group 1 received propofol anesthesia by a target-controlled-infusion (TCI) pump and group 2 received sevoflurane anesthesia. Non-invasive blood pressure, heart rate, and end-expiration CO2 partial pressure were monitored during anesthesia. The depth of anesthesia was measured using the bispectral index (BIS), and maintained between 50 and 60. During surgery we adjusted the doses of propofol and sevoflurane according to the BIS. Samples of peripheral blood were taken before the induction of anesthesia (T1), after the induction of anesthesia (T2), at the beginning of surgery (T3), at the end of surgery (T4) and on the first day after surgery (D1). Blood samples were analyzed to give the Th1/Th2 ratio and plasma level of cortisol.

RESULTSNon-invasive blood pressure, heart rate and end-expiration CO2 partial pressure were not notably different in the two groups. At T4, the percentage of T1 cells was higher in group 1 and had statistical significance (P < 0.05). The percentage of T2 cells was not significantly different in the two groups. At T4, the difference in the Th1/Th2 ratio was significantly different. At T3, T4, and D1, the plasma level of cortisol was lower in group 1 (P < 0.05).

CONCLUSIONCompared with sevoflurane, propofol can preferably promote Th cells to differentiate into Th1 cells and inhibit surgical stress. Propofol may therefore be immunoprotective for such patients.

Adult ; Cell Differentiation ; drug effects ; Female ; Flow Cytometry ; Humans ; Hydrocortisone ; blood ; Male ; Methyl Ethers ; pharmacology ; therapeutic use ; Middle Aged ; Propofol ; pharmacology ; therapeutic use ; T-Lymphocytes, Helper-Inducer ; cytology ; drug effects ; Th1 Cells ; cytology ; drug effects ; Th2 Cells ; cytology ; drug effects

AIMTo explore the effect of propofol preconditioning on cardiomyocyte apoptosis and cytochrome C release from mitochondria during mild hypothermic ischemia/reperfusion in isolated rat hearts.

METHODS50 isolated SD rat hearts perfused on Langendorff apparatus were randomly divided into 5 groups (n=10): control group (C), DMSO group (D), 3 different concentrations of propofol groups of 25 micromol x L(-1) (P1), 50 micromol x L(-1) (P2), 100 micromol x L(-1) (P3) propofol respectively. All of the isolated rat hearts were subjected to 31 degrees C mild hypothermic ischemia for 55 min followed by 60 min reperfusion. The D, P1, P2, P3 groups were preconditioned by perfusing with K-H solution containing 20 micromol x L(-1) DMSO and 25, 50, 100 micromol x L(-1) propofol respectively for 10 min and then followed by 5 min K-H solution washing out before ischemia. The preconditioning procedure was repeated twice. Hemodynamics of the hearts was recorded after equilibration(baseline values) immediately before ischemia, 30 min and 60 min after reperfusion respectively. Cardiomyocyte apoptosis rate and contents of cytosolic and mitochondrial cytochrome C were measured at the end of reperfusion.

RESULTSAfter 30 min and 60 min reperfusion, LVEDP was significantly lower and LVDP was significantly higher in P3 group than those in C group ( P < 0.05, P < 0.01). Compared with C group, cardiomyocyte apoptosis rate of the hearts decreased significantly in P2,P3 groups at the end of reperfusion (P < 0.05, P < 0.01). Cytochrome C level increased significantly in mitochondria but decreased significantly in cytosol in P2, P3 groups as compared with C group (P < 0.05, P < 0.01).

CONCLUSIONPropofol preconditioning decreased cardiomyocyte apoptosis, protected the heart against 31 degrees C mild hypothermic ischemia/reperfusion injury by attenuation of the release of cytochrome C from mitochondria to cytosol.

Animals ; Apoptosis ; drug effects ; physiology ; Cytochromes c ; metabolism ; Hypothermia, Induced ; In Vitro Techniques ; Ischemic Preconditioning ; methods ; Male ; Mitochondria, Heart ; metabolism ; Myocardium ; metabolism ; pathology ; Propofol ; pharmacology ; therapeutic use ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; prevention & control

AIMTo investigate the role of oxygen free radicals (OFR) in hepatic ischemia and reperfusion injury (HI/RI) and effect of propofol on them.

METHODSThe rabbits were randomly divided into three groups (n=10), sham operated group (Control), HIR group(I/R) and HIR + propofol group (PRO). Changes of several parameters which included malondialdehyde (MDA), superoxide dismutase (SOD), xanthine oxidase (XO) and alanine aminotransferase(ALT) were measured before ischemia, 45 minutes after ischemia and 45 minutes after reperfusion in plasma. Meanwhile MDA concentration, SOD, XO activities and ALT value in liver tissue were measured, and the ultrastructure changes in liver tissue were observed under electron microscope at 45 minutes after reperfusion.

RESULTSAs compared with group control, XO, MDA and ALT increased and SOD decreased during HI/RI (P < 0.05 and P < 0.01) in plasma, and XO, MDA increased as well as SOD decreased at 45 minutes after reperfusion (P < 0.05 and P < 0.01) in liver tissue and there were abnormal changes of the hepatic ultrastructure at 45 minutes after reperfusion. Propofol reversed the results of mentioned indices as above markedly (P < 0.05 and P < 0.01).

CONCLUSIONOFR is an important factor during HI/RI, propofol may attenuate hepatic ischemia-reperfusion injury by dropping OFR level (raising SOD activity and dropping XO activity) and antagonizing lipid pe-reoxidation (reducing MDA content).

Alanine Transaminase ; metabolism ; Animals ; Free Radical Scavengers ; metabolism ; Liver ; blood supply ; ultrastructure ; Malondialdehyde ; metabolism ; Oxidation-Reduction ; drug effects ; Propofol ; pharmacology ; therapeutic use ; Rabbits ; Reactive Oxygen Species ; metabolism ; Reperfusion Injury ; drug therapy ; metabolism ; Superoxide Dismutase ; metabolism ; Xanthine Oxidase ; metabolism

BACKGROUNDThere are few studies to assess whether propofol attenuates myocardial ischemia-reperfusion injury via a mechanism related to nitric oxide (NO) route, so we designed this randomized blinded experiment to observe the changes of NO contents, nitric oxide synthase (NOS) activity, NOS contents in the myocardium, and cardiac function in ischemic reperfused isolated rat hearts, and to assess the relation between myocardial NO system and cardioprotection of propofol.

METHODSThe hearts of 30 Sprague-Dawley male rats were removed, mounted on a Langendorff apparatus, and randomly assigned to one of three groups (n = 10 each group) to be treated with the following treatments in a blinded manner: Group 1, control group, after perfusion with pure Krebs Henseleit bicarbonate (K-HBB) buffer solution for 15 minutes, hearts were subjected to 20 minutes global ischemia followed by 60 minutes reperfusion with pure K-HBB buffer; Group 2, after perfusion with K-HBB buffer solution containing propofol (10 microg/ml) for 15 minutes, the hearts underwent 20 minutes global ischemia followed by 60 minutes reperfusion with the same K-HBB buffer solution; Group 3, after perfusion with K-HBB buffer solution containing propofol (10 microg/ml) and L-NAME (100 micromol/L) for 15 minutes, the hearts underwent 20 minutes global ischemia followed by 60 minutes reperfusion with the same K-HBB buffer solution. The cardiac function was continuously monitored throughout the experiment. The coronary flow was also measured. An ISO-NO electrode was placed into the right atrium close to the coronary sinus to continuously measure NO concentration in the coronary effluent. The tissue samples from apex of hearts in Groups 1 and 2 were obtained to measure the NOS activity by spectrophotometry and the NOS contents by immunohistochemistry, respectively.

RESULTSThe cardiac function was significantly inhibited after ischemia and then gradually improved with reperfusion in all three groups. As compared with Group 1, the cardiac function variables and coronary flow at all the observed points were significantly improved in Group 2. The cardiac function variables and coronary flow were better in Group 3 than in Group 1, but were inferior in Group 3 than in Group 2. Both NO contents and NOS activity in the myocardium were significantly higher in Group 2 than in Group 1. However, NOS contents in the myocardium did not significantly differ between Groups 1 and 2.

CONCLUSIONSIn isolated rat hearts, propofol can improve cardiac functional recovery after ischemia-reperfusion by upregulating NOS activity in the myocardium. The NO system may play an important role in the preservation of myocardial ischemia-reperfusion injury produced by propofol.

Animals ; Coronary Circulation ; drug effects ; Enzyme Activation ; drug effects ; Heart ; drug effects ; Heart Function Tests ; Hypnotics and Sedatives ; pharmacology ; therapeutic use ; Immunohistochemistry ; In Vitro Techniques ; Male ; Myocardial Reperfusion Injury ; drug therapy ; enzymology ; Myocardium ; enzymology ; Nitric Oxide Synthase ; metabolism ; Propofol ; pharmacology ; therapeutic use ; Rats ; Rats, Sprague-Dawley

The neuroprotective effect of propofol against intracerebral hemorrhage (ICH) in rats was investigated. ICH was induced in rats by infusion of collagenase (Type VII) 0.5 U (1 U x microL(-1)) into the left caudate nucleus. Three doses of propofol were given intraperitoneally (i.p.) 10 min before collagenase infusion. Effects of propofol on neurological behavioral scores, brain water content (BWC), activity of superoxide dismutase (SOD) and content of malondialdehyde (MDA) in brain tissue, expression level of caspase-3 were studied. In propofol groups (30 and 100 mg x kg(-1)), the neurological behavioral score, BWC and the content of MDA were significantly lower than those in ICH group (P < 0.05, P < 0.01), whereas the activity of SOD was higher than that in ICH group (P < 0.05). Meanwhile, propofol (15, 30, and 100 mg x kg(-1)) inhibited caspase-3 expression in dose-dependent manner (r = 0.877). Brain damages caused by ICH in rats can be alleviated by propofol, which mechanism might be attributed to its antioxidant activity.
Animals ; Behavior, Animal ; drug effects ; Brain ; metabolism ; Brain Edema ; drug therapy ; etiology ; Caspase 3 ; metabolism ; Cerebral Hemorrhage ; chemically induced ; complications ; metabolism ; physiopathology ; Collagenases ; Male ; Malondialdehyde ; metabolism ; Neuroprotective Agents ; pharmacology ; therapeutic use ; Propofol ; pharmacology ; therapeutic use ; Rats ; Rats, Sprague-Dawley ; Superoxide Dismutase ; metabolism