Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Propofol”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 721 records · Page 40Linked to original sources
PubMed1989

The pharmacology of propofol.

A review of the pharmacology of propofol, a new IV anesthetic agent, is presented. Solubilized in a soybean emulsion, propofol is one of a series of sterically hindered phenols that exhibit anesthetic activity. Induction of anesthesia with propofol may be associated with pain on injection, apnea, and a reduction in arterial blood pressure (BP) and cardiac output. Caution should be ascribed to its use in patients with coronary artery disease, where these effects may have the potential for producing myocardial ischemia. The hemodynamic responses to laryngoscopy and intubation are attenuated. The pharmacokinetic profile suggests suitability as an infusion for either maintenance of anesthesia or sedation. Use of propofol as an infusion during surgery may result in a further reduction in cardiac output, particularly with the concomitant administration of adjuvant increments of fentanyl. The ventilatory response to CO2 is depressed during such an infusion. The high clearance of propofol suggests that even after a prolonged infusion, recovery should be rapid. This finding has been confirmed in a series of studies establishing propofol as an ideal agent for use in a total IV anesthetic technique. Both the quality and speed of recovery, together with the absence of emetic sequelae, support the use of propofol in an outpatient setting. Propofol appears to have no long-term effect on adrenocortical function and appears safe for use in patients with acute intermittent porphyria and susceptibility to malignant hyperpyrexia.

Adult↗
PubMed1995

Propofol-based anesthesia as compared with standard anesthetic techniques for middle ear surgery.

STUDY OBJECTIVE: To determine if a total intravenous (i.v.) technique with propofol and fentanyl is superior to isoflurane anesthesia in patients undergoing middle ear surgery. DESIGN: Prospective, randomized study. SETTING: Inpatient otolaryngology service at a university medical center. PATIENTS: 102 ASA status I and II nonobese patients with no significant history of diabetes, chronic cholecystitis, neuropathy, or neuromuscular disorders that could produce delayed gastric emptying. INTERVENTIONS: Patients were admitted to the study and randomly divided into three equal groups. I.V. administration of thiopental sodium 5 mg/kg for induction of anesthesia followed by 60% air/oxygen (O2) with isoflurane 1% to 2% end-tidal for maintenance anesthesia (group 1). The same anesthetic was given as above, with the addition of droperidol 25 mcg/kg given after induction (group 2). I.V. administration of propofol 2 mg/kg for induction of anesthesia followed by propofol 50 to 250 mcg/kg/min for maintenance anesthesia. All groups received fentanyl 3 mcg/kg i.v. after induction. MEASUREMENTS AND MAIN RESULTS: Surgical duration, induction, maintenance, and total anesthesia times were recorded in addition to eye opening and extubation. Intergroup comparisons of postoperative nausea, vomiting, and pain were done, as were recovery scores using the Steward system. Patients receiving propofol had significantly less nausea than those receiving isoflurane only (4 of 34 versus 12 of 34, p < 0.05) as well as vomiting (2 of 34 versus 8 of 34, p < 0.05). Immediate recovery scores were significantly better for propofol compared with the isoflurane/droperidol group. Recovery at 30 minutes was also faster with propofol compared with isoflurane or isoflurane/droperidol (5.7 +/- 0.1 min versus 5.1 +/- 0.2 min and 5.2 +/- 0.2 min, p < 0.05). CONCLUSIONS: Propofol-fentanyl seems to be a better anesthetic than isoflurane-fentanyl in reducing the incidence of nausea and vomiting after middle ear surgery. Through the addition of droperidol to the isoflurane anesthetic seemed as effective, emergence from anesthesia was slower. For middle ear surgeries producing emesis, propofol-based anesthetics produced a rapid emergence with less nausea and vomiting.

Adjuvants, Anesthesia↗
PubMed1996

Propofol infusion for induction and maintenance of anesthesia in elderly patients: recovery and hemodynamic profiles.

STUDY OBJECTIVE: To evaluate the effect of propofol infusion for both induction and maintenance of anesthesia on hemodynamics and recovery in elderly patients compared with conventional thiopental-isoflurane anesthesia. DESIGN: Randomized, prospective, study. SETTING: Teaching hospital. PATIENTS: 60 nonpremedicated ASA physical status I, II, and III adult elderly patients scheduled to undergo total hip replacement surgery. INTERVENTIONS: Patients received either intravenous propofol infusion at 0.75 mg/kg/min or thiopental bolus 2 to 4 mg/kg for induction, followed by variable-rate propofol infusion up to 0.15 mg/kg/min or isoflurane 0.5% to 1.5% for maintenance of anesthesia. Nitrous oxide and fentanyl supplements were given in all patients. MEASUREMENTS AND MAIN RESULTS: Perioperative hemodynamic changes, patient recovery profile, and myocardial ischemia incidents were assessed in both anesthetic groups. Induction of anesthesia by propofol infusion (1.6 mg/kg) did not produce significant hypotension (-8.3% +/- 5.5%) or bradycardia; these changes were similar to induction by thiopental bolus injection (3.3 mg/kg). Furthermore, increases in blood pressure and heart rate (HR) during endotracheal intubation were limited to 6% following propofol induction compared with 22% for thiopental induction. During maintenance of anesthesia, the decrease in MAP and HR was comparable in both anesthetic groups. Postanesthetic recovery times for patient to achieve wakefulness, mental orientation, and a maximum Aldrete score (10) were significantly faster in the propofol group, by 4 minutes, 6 minutes, and 20 minutes, respectively; however, the time to discharge from the postanesthesia care unit was not different. Holter-monitored perioperative myocardial ischemic events detected in 23% of the patients occurred independent of hemodynamic changes or the type of anesthetic administered. CONCLUSION: Induction of anesthesia by propofol infusion in elderly patients produces greater attenuation of cardiovascular sympathetic response than thiopental bolus induction. Induction and maintenance of anesthesia by propofol infusion results in more rapid recovery in our elderly patients than thiopental isoflurane anesthesia.

Aged↗
PubMed2004

Effects of low-dose midazolam with propofol in patient-controlled sedation (PCS) for apicectomy.

We studied the effects of low-dose midazolam with propofol for patient control sedation (PCS) in 30 healthy (ASA grade I) patients who were randomly allocated into two equal groups (n = 15 in each). They were given a propofol infusion of 2mg/kg/h after a bolus dose of 0.7 mg/kg. The second group was given the 2mg/kg/h propofol infusion after a dose of midazolam 0.03 mg/kg and a bolus dose of propofol 0.7 mg/kg. The standard dose for PCS was propofol 0.2mg/kg in both groups. Clinical data were taken and haemodynamic variables, and oxygen saturation were recorded before and on the 5th, 10th, 20th, and 30th minutes during the operations. The level of sedation, amnesia and conditions of each patient were evaluated during the study. Patients' satisfaction was recorded using a modified visual analogue scale (VAS). All results were evaluated statistically. We conclude that low-dose midazolam with propofol during PCS neither reduced oxygen saturation nor prolonged the time of discharge. Low-dose midazolam with propofol also improved the acceptability and comfort for patients and made the operation easier, which makes it preferable to propofol alone.

Adolescent↗
PubMed2004

Quantification of lipid bilayer effective microviscosity and fluidity effect induced by propofol.

Electron spin resonance (ESR) spectroscopy with nitroxide spin probes was used as a method to probe the liposome microenvironments. The effective microviscosities have been determined from the calibration of the ESR spectra of the probes in solvent mixtures of known viscosities. In the first time, by measuring ESR order parameter (S) and correlation time (tau(c)) of stearic spin probes, we have been able to quantify the value of effective microviscosity at different depths inside the liposome membrane. At room temperature, local microviscosities measured in dimyristoyl-l-alpha phosphatidylcholine (DMPC) liposome membrane at the different depths of 7.8, 16.95, and 27.7 A were 222.53, 64.09, and 62.56 cP, respectively. In the gel state (10 degrees C), those microviscosity values increased to 472.56, 370.61, and 243.37 cP. In a second time, we have applied this technique to determine the modifications in membrane microviscosity induced by 2,6-diisopropyl phenol (propofol; PPF), an anaesthetic agent extensively used in clinical practice. Propofol is characterized by a unique phenolic structure, absent in the other conventional anaesthetics. Indeed, given its lipophilic property, propofol is presumed to penetrate into and interact with membrane lipids and hence to induce changes in membrane fluidity. Incorporation of propofol into dimyristoyl-l-alpha phosphatidylcholine liposomes above the phase-transition temperature (23.9 degrees C) did not change microviscosity. At 10 degrees C, an increase of propofol concentration from 0 to 1.0 x 10(-2) M for a constant lipid concentration mainly induced a decrease in microviscosity. This fluidity effect of propofol has been qualitatively confirmed using merocyanine 540 (MC540) as lipid packing probe. Above 10(-2) M propofol, no further decrease in microviscosity was observed, and the microviscosity at the studied depths (7.8, 16.95, and 27.7 A) amounted 260.21, 123.87, and 102.27 cP, respectively. The concentration 10(-2) M was identified as the saturation limit of propofol in dimyristoyl-l-alpha phosphatidylcholine liposomes.

Biophysical Phenomena↗
PubMed2006

Influence of external and intracellular pH on propofol-induced responses in rat locus coeruleus neurons.

The effect of external and intracellular pH on propofol-induced responses in rat locus coeruleus neurons was examined using intracellular recording from in vitro brain slice preparations. Experimental variation of external pH from 7.34 to 6.81 did not affect the propofol-induced responses. In contrast, raising the external pH from 7.34 to 8.10 resulted in enhanced 100 microM propofol effects. The effects were 1.8 times greater on membrane hyperpolarization (pH 8.10: 11.8 +/- 1.3 mV; pH 7.34: 6.5 +/- 1.0 mV, n = 5) and 1.5 times greater on reduction in input resistance (pH 8.10: 38.2 +/- 6.3%; pH 7.34: 24.7 +/- 4.1%, n = 5). Cytosolic acidification was used in which 1/3 NaCl in artificial cerebrospinal fluid was replaced with weak organic acids--sodium acetate. It did not significantly affect the propofol-induced responses. On the other hand, intracellular alkalinization with 5 mM NH(4)Cl markedly suppressed the 100 microM propofol-induced membrane hyperpolarization (1.0 +/- 0.6 mV; control: 13.9 +/- 0.9 mV, n = 5) and reduction of input resistance (38.1 +/- 1.3%; control: 61.0 +/- 4.3%, n = 5). However, the presence of 3-5 mM ammonium acetate also showed the similarly suppressing effect on membrane hyperpolarization (1.7 +/- 0.6 mV; control: 9.2 +/- 1.8 mV, n = 5) and reduction of input resistance (28.5 +/- 8.5%; control: 37.0 +/- 6.3%, n = 5) caused by 100 microM propofol. We suggested that the main suppressing effect of NH(4)Cl results from ammonium ion, but not intracellular alkalinization. Furthermore, we examined the feature of pharmacological regulation of propofol-induced responses by pentobarbital or alphaxalone during pH changes. It appears that neither pentobarbital nor alphaxalone could allosterically modulate the propofol-induced responses, which had been affected by pH changes.

Acidosis↗
PubMed2005

Comparison of the effects of propofol and midazolam on the cardiovascular autonomic nervous system during combined spinal and epidural anesthesia.

STUDY OBJECTIVE: To investigate the effect of propofol and midazolam on cardiac autonomic nervous system (CANS) activity during combined spinal-epidural anesthesia. DESIGN: Prospective, clinical study. SETTING: Operating room of a university hospital. PATIENTS: Forty ASA physical status I and II patients scheduled for knee surgery. INTERVENTION: Patients were randomized to receive sedation with either propofol or midazolam. MEASUREMENTS: Heart rate (HR), HR variability (HRV), systolic arterial pressure (SAP), and SAP variability (SAPV) were used for the analysis. These values were measured at the preanesthetic period, after intrathecal injection for spinal anesthesia, after sedation with propofol or midazolam, and just before the end of surgery with sedation. Cross-spectral analyses of the HR and SAP data were assessed to quantify the frequency-related coherence spectra and phase spectra. MAIN RESULTS: Spinal anesthesia itself had no effect on power spectral changes in both groups. After sedation, as for HRV, high-frequency (HF) power (HF, 0.15-0.40 Hz) did not change, whereas low-frequency (LF) power (LF, 0.04-0.15 Hz) and LF/HF, an indicator of CANS balance, significantly decreased with propofol. Further, coherence in cross-spectra presented depression in the LF band area after sedation with propofol. Before the end of surgery with sedation, LF and LF/HF in both HRV and SAPV were correlated with age in those with propofol; however, scarce relation was observed in those who received midazolam. CONCLUSIONS: Propofol was more potent than midazolam in causing CANS activity to be sympatholytic during combined spinal and epidural anesthesia and which was correlated with age only with propofol.

Adult↗
PubMed2005

Development of a rapid and sensitive LC-ESI/MS/MS assay for the quantification of propofol using a simple off-line dansyl chloride derivatization reaction to enhance signal intensity.

A rapid, selective and sensitive method was developed for the determination of propofol concentration using an off-line dansyl chloride derivatization step to enhance signal intensity. The method consisted of a protein precipitation extraction followed by derivatization with dansyl chloride and analysis by liquid chromatography ionspray tandem mass spectrometry (LC-ESI/MS/MS). The separation was achieved using a 100 mm x 2 mm C8 analytical column combined with an isocratic mobile phase composed of 80:20 acetonitrile: 0.5% formic acid in water. Signal intensity of the propofol-dansyl chloride derivative was increased up to 200-fold as compared to the underivatized propofol in positive electrospray mode. An analytical range of 20-20,000 ng/mL was used in the calibration curve of plasma and blood samples. The novel method met all requirements of specificity, sensitivity, linearity, precision, accuracy and stability. A pharmacokinetic study was performed in rats and the novel analytical method was used as a routine analysis to provide enhanced measurements of plasma and blood concentrations of propofol. Blood and plasma pharmacokinetic results show that a very important fraction of propofol distributes into red blood cells. In conclusion, a rapid and sensitive LC-ESI/MS/MS method using a derivatization agent was developed to enhance signal intensity of propofol. Routine analysis with the novel method provided accurate results and enhanced the detection levels of plasma and blood concentrations of propofol to better characterize the in vivo biodisposition of propofol.

Animals↗
PubMed2005

Antioxidant properties of propofol and erythropoietin after closed head injury in rats.

Reactive oxygen species play a role during brain injury due to closed head trauma. Enzymatic or nonenzymatic antioxidants may protect brain tissue against oxidative damage. The present study was performed to assess the changes of endogenous indices of oxidative stress in serum from rats subjected to head trauma and whether treatment with propofol and/or erythropoietin (EPO) modifies the levels of endogenous indices of oxidative stress. For these purposes, female Wistar Albino rats were divided into five groups: non-traumatic sham group, trauma performed control, trauma with propofol (i.p.), trauma with EPO (i.p.) and trauma with propofol and EPO performed study groups. At the end of the experimental procedure, blood was taken by cardiac puncture to determine superoxide dismutase (SOD) and xanthine oxidase (XO) activities as well as malondialdehyde (MDA) and nitric oxide (NO) levels in serum. Serum MDA level of control traumatic brain injury (TBI) group was significantly higher than sham operation group (p<0.012). Serum MDA levels in propofol, EPO and propofol+EPO groups were found to be decreased in comparison with control group (p<0.039, p<0.030 and p<0.018, respectively). Serum NO level was found to be increased in TBI group, but difference was not statistically significant when compared to sham-operated group (p=0.092). Propofol, EPO and propofol+EPO administration efficiently reduced serum NO levels to reach sham-operated group (p<0.002, p<0.001 and p<0.015, respectively). These results suggested that acute administration of both propofol and EPO altered the indices of oxidative stress similarly against brain injury due to trauma.

Analysis of Variance↗
PubMed2004

Does propofol anesthesia affect intraoperative parathyroid hormone levels? A randomized, prospective trial.

BACKGROUND: Intravenous propofol (2,6-diisopropylphenol) infusion is used commonly for sedation/anesthesia during operations. Several authors have reported that propofol can interfere with intact parathyroid hormone (PTH) testing in vitro. Therefore, many surgeons avoid propofol during parathyroidectomy. METHODS: To determine whether propofol affects intraoperative PTH levels in vivo, we randomly assigned 34 patients (80% power; alpha < .05) with secondary hyperparathyroidism to undergo surgery for dialysis access. Patients were assigned randomly to local anesthesia with either propofol (n = 17 patients) or midazolam (n = 17 patients) sedation. PTH values were obtained before the procedure and at 10 minutes and 30 minutes after the start of the propofol or midazolam. RESULTS: Median preoperative serum PTH and calcium levels were 175 pg/mL (range, 27-2646 pg/mL) and 9.2 mg/dL (range, 8.1-10.8 mg/dL), respectively. There was no statistically significant difference between the PTH levels in the 2 groups at each of our time points. There was also no difference in the percentage of change from baseline in the PTH values between our 2 groups. No patient in either group had a sustained drop in their PTH level of greater than 50%. CONCLUSIONS: Intravenous propofol infusion does not alter PTH levels significantly during the operation. Therefore, we believe the intraoperative PTH assay can be used safely during propofol sedation when parathyroid surgical procedures are being performed.

Anesthetics, Intravenous↗
PubMed2003

Comparative effects of propofol versus fentanyl on cerebral oxygenation state during normothermic cardiopulmonary bypass and postoperative cognitive dysfunction.

BACKGROUND: The purpose of this study was to examine the comparative effects of propofol and fentanyl on cerebral oxygenation during normothermic cardiopulmonary bypass and postoperative cognitive dysfunction. METHODS: One hundred eighty patients scheduled for elective coronary artery bypass grafting were randomly divided into two groups: propofol group (n = 90) and fentanyl group (n = 90). After induction of anesthesia, a fiberoptic oximetry oxygen saturation catheter was inserted into the right jugular bulb to monitor jugular venous oxygen hemoglobin saturation continuously. Hemodynamic measurements and arterial and jugular venous blood gases were measured at seven time points. All patients underwent a battery of neurologic and neuropsychological tests on the day before the operation and at 6 months after the operation. RESULTS: Cerebral desaturation (defined as a jugular venous oxygen hemoglobin saturation value less than 50%) during cardiopulmonary bypass was more frequent in the fentanyl group than in the propofol group. Cerebral desaturation time (duration when jugular venous oxygen hemoglobin saturation was less than 50%) and the ratio of cerebral desaturation time to total cardiopulmonary bypass time in the fentanyl group differed significantly from those in the propofol group (fentanyl group: 27 +/- 14 minutes, 20% +/- 9%; propofol group: 18 +/- 11 minutes, 14% +/- 7%, respectively, p < 0.05). There was no significant difference in postoperative cognitive dysfunction at 6 months after operation between the two groups (propofol group: 5 of 77, 6%; fentanyl group: 5 of 75, 7%). CONCLUSIONS: Propofol preserved cerebral oxygenation state estimated by jugular venous oxygenation during cardiopulmonary bypass compared with the fentanyl group. However, propofol did not affect postoperative cognitive dysfunction.

Aged↗
PubMed2000

Intracerebroventricular propofol is neuroprotective against transient global ischemia in rats: extracellular glutamate level is not a major determinant.

Excessive glutamate accumulation in extracellular space due to ischemia in the central nervous system (CNS) is believed to initiate the cascade toward irreversible neuronal damage. An intravenous general anesthetic, propofol (2,6-diisopropylphenol) has been implicated to be neuroprotective against cerebral ischemia. The purpose of this study was to test the hypothesis that intracerebroventricular propofol produced a reduction in extracellular glutamate level during global ischemia and the resultant neuroprotection. Adult male Wistar rats were anesthetized with halothane in nitrous oxide/oxygen and mechanically ventilated. Propofol (3 or 10 mg/kg), Intralipid((R)) as a vehicle for propofol, or artificial cerebrospinal fluid (aCSF) was administered into the cerebral ventricles 15 min prior to a 10-min forebrain ischemia elicited by the four-vessel occlusion. Extracellular glutamate concentration in the hippocampal CA1 was continuously monitored during the peri-ischemic period with a microdialysis biosensor. Neuronal cell loss in the hippocampal CA1 was evaluated by cresyl-violet staining of sections 7 days later. Propofol (3 and 10 mg/kg) and Intralipid, compared with aCSF, similarly reduced the extracellular glutamate accumulation during the peri-ischemic period (P<0.05), indicating that the extracellular glutamate reduction that was seen primarily reflects the effect of Intralipid. The number of intact neurons in the hippocampal CA1 in propofol 10 mg/kg-treated rats was significantly higher than that in rats treated with propofol 3 mg/kg, Intralipid, or aCSF (P<0.05). We conclude that intracerebroventricular propofol exhibits neuroprotection against transient global forebrain ischemia; however, the extracellular glutamate level during ischemia is not a major determinant of this neuroprotection.

Animals↗
PubMed2000

Protection of hearts from reperfusion injury by propofol is associated with inhibition of the mitochondrial permeability transition.

OBJECTIVE: Diminishing oxidative stress may protect the heart against ischaemia-reperfusion injury by preventing opening of the mitochondrial permeability transition (MPT) pore. The general anaesthetic agent propofol, a free radical scavenger, has been investigated for its effect on the MPT and its cardioprotective action following global and cardioplegic ischaemic arrest. METHOD: Isolated perfused Wistar rat hearts were subjected to either warm global ischaemia (Langendorff) or cold St. Thomas' cardioplegia (working heart mode) in the presence or absence of propofol. MPT pore opening was determined using [3H]-2-deoxyglucose-6-phosphate ([3H]-DOG-6P) entrapment. The respiratory function of isolated mitochondria was also determined for evidence of oxidative stress. RESULTS: Propofol (2 micrograms/ml) significantly improved the functional recovery of Langendorff hearts on reperfusion (left ventricular developed pressure from 28.4 +/- 6.2 to 53.3 +/- 7.3 mmHg and left ventricular end diastolic pressure from 52.9 +/- 4.3 to 37.5 +/- 3.9 mmHg). Recovery was also improved in propofol (4 micrograms/ml) treated working hearts following cold cardioplegic arrest. External cardiac work on reperfusion improved from 0.42 +/- 0.05 to 0.60 +/- 0.03 J/s, representing 45-64% of baseline values, when compared to controls (P < 0.05). Propofol inhibited MPT pore opening during reperfusion, [3H]-DOG-6P entrapment being 16.7 vs. 22.5 ratio units in controls (P < 0.05). Mitochondria isolated from non-ischaemic, propofol-treated hearts exhibited increased respiratory chain activity and were less sensitive to calcium-induced MPT pore opening. CONCLUSION: Propofol confers significant protection against global normothermic ischaemia and during cold cardioplegic arrest. This effect is associated with less opening of mitochondrial MPT pores, probably as a result of diminished oxidative stress. Propofol may be a useful adjunct to cardioplegic solutions in heart surgery.

Analysis of Variance↗
PubMed2002

Propofol reduces infarct size and striatal dopamine accumulation following transient middle cerebral artery occlusion: a microdialysis study.

Acute cerebral ischemia is associated with an increased extracellular dopamine accumulation. Attenuation or prevention of excessive dopamine accumulation alleviates the cerebral ischemic damage. Propofol, an intravenous anesthetic, has been suggested to have neuroprotective properties. The effect of propofol on dopaminergic neurotransmitters is unclear. The in vivo microdialysis technique was used in this study to examine the effect of propofol on infarct size and striatal dopamine accumulation in rat model of temporary middle cerebral artery occlusion. Sixteen rats were fitted with a right striatal microdialysis probe. Ischemia was induced by inserting a 4-0 monofilament nylon suture into the middle cerebral artery. Propofol was intravenously infused in eight rats during ischemia (60 min) and reperfusion (60 min) at an average dose of 36 mg/kg/h. Control rats (n=8) received vehicle infusion. The infarct size was determined at the end of the experiment. Propofol significantly reduced infarct size, the median (interquatile range) value was 6.84% (7.68%), significantly lower than that in the control group, which was 28.04% (32.28%) (p<0.01). The middle cerebral artery occlusion significantly increased dopamine accumulation in the striatum. Propofol infusion significantly attenuated this middle cerebral artery occlusion-induced dopamine accumulation. The data demonstrate that propofol, when administered during ischemia and reperfusion, provides neuroprotection in our middle cerebral artery occlusion in rat model. The data also suggest that attenuated dopamine accumulation may be one of the factors contributing to the neuroprotective property of propofol.

Animals↗
PubMed1997

The effect of propofol on parthenogenetic activation, in vitro fertilization and early development of mouse oocytes.

OBJECTIVE: To assess the effect of propofol on fertilization and early embryo development in a mouse IVF model. DESIGN: Controlled study. SETTING: Mouse IVF. INTERVENTION(S): Mouse oocytes were exposed in vitro to propofol at a concentration of 0 (control), 50, 250, 500, 1,000, or 5,000 ng/mL for 30 minutes, washed, and inseminated. Thereafter, fertilization was assessed. Subsequent in vitro development to the blastocyst stage was monitored daily. The potential to activate parthenogenetically oocytes also was evaluated by looking for spontaneous extrusion of the second polar body or development to the two-cell stage. In a second step, a pure propofol solution was added to culture medium and used as a standard. MAIN OUTCOME MEASURE(S): Two-cell and blastocyst-stage embryo. RESULT(S): Where fertilization occurred, subsequent embryo cleavage and development up to the blastocyst stage was affected significantly by the presence of propofol solution in the medium, (i.e., 3% to 41%) in comparison with the control group (76%). Exposure of unfertilized oocytes for 30 minutes to propofol results in a parthenogenetic activation of 33% to 60%, which was significantly higher than the control (10%). When oocytes were kept in propofol for 24 hours, a mean of 30% of activation was observed as compared with 0.5% for the control. CONCLUSION(S): We can conclude from these experiments that even a brief exposure of cumulus-enclosed oocytes to a low concentration of propofol is deleterious to subsequent cleavage. Exposure of unfertilized oocytes to propofol results in a high degree of parthenogenetic activation.

Anesthetics, Intravenous↗
PubMed2001

Propofol-induced cytochrome P450 inhibition: an in vitro and in vivo study in rats.

Propofol, a widely used anesthetic drug, is known to inhibit cytochrome P450 activities in vitro. The goal of this study was to compare cytochrome P450 activities in vitro and in vivo in presence of propofol. In vitro (liver microsomes and freshly isolated hepatocytes), cytochrome P450 IA2 and IIB1 activities were measured as the production of resorufin from ethoxy- and pentoxyresorufin, respectively, in presence of various concentrations of propofol. In vivo, cytochrome P450 activities were assessed as the production of 13CO2 from 13C-aminopyrine injected intravenously, during acute administration or after chronic treatment. In vitro results confirmed the dose-dependent inhibitory effect of propofol on cytochrome P450 activities, both on liver microsomes and isolated hepatocytes. In vivo, the acute administration of propofol induced a significant decrease of 13C-aminopyrine metabolism. Chronic treatment with propofol induced a significant inhibition of 13C-aminopyrine metabolism only after 2 weeks. No enzyme induction was observed. In conclusion, our results demonstrate that propofol inhibits cytochrome P450 also in vivo. Drug interactions may thus occur during propofol administration.

Aminopyrine↗
PubMed2000

Inhibition of 5-HT3 receptors by propofol: equilibrium and kinetic measurements.

Patch-clamp/rapid solution exchange experiments as well as tracer ([14C]-guanidinium) influx measurements were applied to investigate effects of propofol on 5-HT3 receptor channels and compare the results with those obtained with pentobarbital. Currents induced by 30 microM 5-HT were recorded in outside-out patches from N1E-115 cells. Application of propofol 45 s before and during 5-HT application inhibited peak-currents and integrated current responses in a concentration-dependent manner (IC50 values=14.5 and 10.5 microM; Hill coefficients -1.5 and -1.3, respectively). The inhibitory effect of propofol in the current measurements was similar to the propofol-induced inhibition in tracer influx experiments in whole N1E-115 cells (Barann et al., 1993. Naunyn-Schmiedeberg's Archives of Pharmacology 347, 125-132). Pentobarbital-induced inhibition of 5-HT3 receptors in both patch-clamp (Barann et al., 1997. Neuropharmacology 36, 655-664) and tracer influx measurements indicated a lower potency and lower slope (IC50 values=130 and 55 microM; Hill coefficients -0.8 and -0.7, respectively) compared to propofol. Propofol, in contrast to pentobarbital, showed nearly the full potency when applied to the patches exclusively 45 s before 5-HT. Propofol was least effective when administered exclusively during 5-HT. The onset of inhibition of 5-HT-induced peak currents by propofol had a time constant of 220 ms, similar to the kinetics of 5-HT-induced desensitization.

Anesthetics, General↗
PubMed1997

Responses to propofol in relation to GABA functionality of discrete parts of the brain of rats.

Genetically-determined regional differences in the GABA-ergic make-up of the brain exist in two lines of Wistar rats viz apomorphine-susceptible (APO-SUS) and apomorphine-unsusceptible (APO-UNSUS) Wistar rats, Propofol is a GABA-mimetic general anesthetic. This study compared the responses to propofol in APO-SUS and APO-UNSUS rats. Propofol induced a higher incidence of involuntary muscular contractions and oral movements, but a lower incidence of grooming, in APO-SUS rats than in APO-UNSUS rats. Reflex inhibition and narcosis, being defined as the behavior marked by both full absence of purposeful movements and by complete loss of righting reflexes, after propofol did not differ between the two lines. APO-SUS rats had less variation of the heart rates and greater variations of diastolic arterial pressures in response to electrical stimulation than the APO-UNSUS rats, and these variations were reduced by increasing doses of propofol. Arterial pressures in APO-SUS rats were higher than in APO-UNSUS rats. Propofol caused a biphasic change in intra-arterial pressures and had the greatest effect in APO-SUS rats. Differences in cerebral GABA transmission, especially in the striato-nigro-collicular pathway, did not give rise to differences in the effect of propofol on narcosis and hindlimb withdrawal reflex. In contrast, these differences in GABA transmission were accompanied by line-specific differences in effect of propofol on certain behavioral and cardiovascular parameters.

Anesthesia, Intravenous↗