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Effects of propofol on extracellular acidification rates in primary cortical cell cultures: application of silicon microphysiometry to anaesthesia.

Propofol depresses both cerebral oxygen consumption and glucose utilization. We tested the hypothesis that these well described effects on brain metabolism are manifest by a reduction in neuronal acid production in vitro. The rate of extracellular acidification in primary cell cultures of rat cortical neurones was measured using a novel instrument (silicon microphysiometer) after stimulation with propofol 0.3, 3 and 30 micrograms ml-1. Intralipid 10% served as a control. Propofol 3 micrograms ml-1 caused a mean decrease of 1.51 (SEM 0.71)% in baseline acidification rate, which was significantly greater than that produced by 0.3 microgram ml-1 or Intralipid alone (P < 0.05). The reduction after stimulation with propofol 30 micrograms ml-1 was 4.68 (0.35)% of baseline rates and this in turn was significantly greater than that elicited by propofol 3 or 0.3 microgram ml-1, or Intralipid (P < 0.001). We have confirmed the depressant effect of propofol on cerebral metabolism and established that propofol inhibits neuronal acid excretion in vitro.

Anesthetics, Intravenous↗

Effects of target-controlled infusion of propofol on the transient hyperaemic response and carbon dioxide reactivity in the middle cerebral artery.

The transient hyperaemic response (THR) of blood flow velocity in the middle cerebral artery (vmca), measured by transcranial Doppler ultrasonography (TCD), can be used to assess cerebral autoregulation. We have studied the effects of propofol administered by target-controlled infusion on vmca, THR and carbon dioxide reactivity. We studied 20 healthy adult patients undergoing elective surgery. A standardized anaesthetic comprising alfentanil 10 micrograms kg-1, propofol via a target-controlled infusor and vecuronium 0.1 mg kg-1 was used in both parts of the study. In the first part, THR tests were performed on 10 subjects while awake and then at an 'induction' target concentration of propofol (the target at which consciousness was lost, mean 6.7 (SD 1.1) micrograms ml-1). In the carbon dioxide study, reactivity was tested in 10 patients while awake and at the 'induction' target concentration of propofol by altering the end-tidal carbon dioxide partial pressure by 1 kPa either side of baseline. Propofol caused a significant decrease in vmca but indices of autoregulation, THR ratio and strength of autoregulation increased significantly. Propofol had no effect on carbon dioxide reactivity. These results suggest that propofol may have a beneficial effect on cerebral haemodynamics.

Adolescent↗

Anaesthesia with propofol decreases FMLP-induced neutrophil respiratory burst but not phagocytosis compared with isoflurane.

Propofol has been reported to produce a dose-dependent inhibition of phagocytosis and superoxide anion production during the respiratory burst (RB) of polymorphonuclear cells (PMNs) in vitro. In this randomized, blinded study, these two parameters were compared during propofol or isoflurane anaesthesia in patients undergoing elective interventional embolization of cerebral arterio-venous malformations. Anaesthesia was performed with continuous intravenous propofol 6-8 mg kg-1 h-1 (n = 15) or isoflurane 0.8-1.0% end tidal (n = 15). Heparinized blood was drawn before, and 2 and 4 h after induction of anaesthesia. The RB in isolated leucocytes was measured with the fluorescent dye rhodamine after ex vivo induction by Escherichia coli or tumour necrosis factor alpha/N-formyl-methionyl-leucylphenylalanine (TNF-alpha/FMLP). Phagocytosis was carried out in whole blood after incubation with fluorescein isothiocyanate (FITC)-labelled, opsonized E. coli and also measured with a flow cytometer. The two groups were similar in terms of biometric data and haemodynamic responsiveness. After 4 h of propofol or isoflurane anesthesia, the mean (SD) phagocytosis of E. coli was 93.2% (7.0%) and 94.3% (9.2%), respectively, of that before anaesthesia. The percentage of PMN with RB activity following TNF-alpha/FMLP stimulation was significantly reduced after 2 h (80.9% (24.2%); P < 0.05) and 4 h (53.7% (27.3); P < 0.05) of anaesthesia with propofol compared with the values before induction. This effect of propofol anaesthesia was significantly different from the effect of isoflurane anaesthesia. In contrast to published in vitro results, 4 h of anaesthesia with propofol did not reduce the phagocytotic capacity of human blood PMN more than isoflurane anaesthesia.

Adolescent↗

Effects of fentanyl, alfentanil, remifentanil and sufentanil on loss of consciousness and bispectral index during propofol induction of anaesthesia.

The bispectral index (BIS) and a sedation score were used to determine and compare the effect of propofol in the presence of fentanyl, alfentanil, remifentanil and sufentanil. Seventy-five non-premedicated patients were assigned randomly into five groups (15 in each) to receive fentanyl, alfentanil, remifentanil, sufentanil or placebo. Opioids were administered using a target-con-trolled infusion device, to obtain the following predicted effect-site concentrations: fentanyl, 1.5 ng ml(-1); alfentanil, 100 ng ml(-1); remifentanil, 6 ng ml(-1); and sufentanil, 0.2 ng ml(-1). After this, a target-controlled infusion of propofol (Diprifusor) was started to increase concentration gradually, to achieve predicted effect-site concentrations of 1, 2, and 4 microg ml(-1). At baseline and at each successive target effect-site concentration of propofol, the BIS, sedation score and haemodynamic variables were recorded. At the moment of loss of consciousness (LOC), the BIS and the effect-site concentration of propofol were noted. The relationship between propofol effect-site concentration and BIS was preserved with or without opioids. In the presence of an opioid, LOC occurred at a lower effect-site concentration of propofol and at a higher BIS50 (i.e. the BIS value associated with 50% probability of LOC), compared with placebo. Although clinically the hypnotic effect of propofol is enhanced by analgesic concentrations of mu-agonist opioids, the BIS does not show this increased hypnotic effect.

Adult↗

Propofol inhibits FMLP-stimulated phosphorylation of p42 mitogen-activated protein kinase and chemotaxis in human neutrophils.

Propofol is used in the peri-operative setting and may affect some neutrophil functions. The effects of propofol on the function and intracellular signal transduction systems of neutrophils is controversial. Mitogen-activated protein kinase families (MAPKs) are members of the intracellular signal-transducing systems in eukaryotes. MAPKs have been shown to be involved in neutrophil chemotaxis by the use of PD98059, the specific inhibitor of MAPK/ERK kinase (MEK). The effects of propofol in dimethyl sulfoxide on phosphorylation of MAPKs and chemotaxis were investigated in human neutrophils. Isolated neutrophils (2 x 10(7) cells per ml) from healthy volunteers were incubated with propofol (2-500 microM) and stimulated by N-formyl-L-methionyl-phenylalanine (FMLP) (100 nM). The effects of propofol on the phosphorylation of p44/42 MAPK were investigated by immunoblotting. The effects of FMLP (1 microM) on chemotaxis were investigated with the under-agarose method. The phosphorylation of p42 MAPK and chemotaxis stimulated by FMLP were both inhibited by propofol at clinically relevant concentrations (> or = 10 and > or = 20 microM respectively). PD98059 (50 microM) also inhibited chemotaxis stimulated by FMLP, suggesting the involvement of p42 MAPK in the response. Propofol might therefore inhibit human neutrophil chemotaxis, at least in part, by suppressing the p44/42 MAPK pathway.

Anesthetics, Intravenous↗

Propofol attenuates myocardial lipid peroxidation during coronary artery bypass grafting surgery.

BACKGROUND: Propofol can scavenge free radicals because it has a chemical structure similar to antioxidants. METHODS: We examined if free radical scavenging occurs with propofol during CABG operations. We studied 24 patients undergoing CABG surgery for triple vessel disease, randomized into two groups. After induction of anaesthesia with fentanyl 10 micrograms kg-1 and midazolam 0.1 mg kg-1, patients in the fentanyl group (n = 14) received fentanyl infusion 10-30 micrograms kg-1 h-1 and patients in the propofol group (n = 10) received propofol infusion 3-6 mg kg-1 h-1 for maintenance of anaesthesia. Atrial tissue biopsies were taken during cannulation for bypass, 45 min after cross-clamp insertion, 5 min after unclamping, and in the decannulation period. Lipid peroxidation was assessed by measurement of thiobarbituric acid reactive substances (TBARS) in the atrial tissue samples. RESULTS: Lipid peroxidation in the propofol group was less than in the fentanyl group (P < 0.05) in all sampling periods. Lipid peroxidation in the fentanyl group increased significantly during cardiopulmonary bypass (CPB) (P < 0.05), but no increase was found in the propofol group (P > 0.05). CONCLUSION: In clinical doses, propofol strongly attenuates lipid peroxidation during CABG surgery.

Aged↗

Pharmacological effects of intravenous melatonin: comparative studies with thiopental and propofol.

BACKGROUND: Possible utility of high-dose i.v. melatonin as an anaesthetic adjuvant has not been studied. This study compared its effects with thiopental and propofol. METHODS: Sprague Dawley rats were assigned to receive bolus or cumulative i.v. doses of melatonin, thiopental or propofol. Righting reflex, hindpaw withdrawal to a noxious stimulus, response to tail clamping and haemodynamic effects were assessed. RESULTS: Melatonin caused a dose-dependent increase in paw withdrawal threshold and the percent of rats displaying loss of the righting reflex. Melatonin was comparable to thiopental and propofol in terms of its rapid onset of hypnosis. The mean ED(50) values for loss of righting reflex were 5.4 (SEM 1.2), 12.5 (1.1) and 178 (1.1) mg kg(-1) for propofol, thiopental and melatonin, respectively. The percent of rats displaying loss of response to tail clamping was greater with propofol than with melatonin (P<0.05). Haemodynamic changes produced by melatonin or propofol were similar in onset and magnitude. CONCLUSIONS: I.V. melatonin can exert hypnotic effects similar to those observed with thiopental and propofol. Melatonin exhibited significant antinociceptive effects but was less effective in abolishing the response to tail clamping.

Adjuvants, Anesthesia↗

Propofol sparing effect of remifentanil using closed-loop anaesthesia.

BACKGROUND: General anaesthesia is a balance between hypnosis and analgesia. We investigated whether an increase in remifentanil blood concentration would reduce the amount of propofol required to maintain a comparable level of anaesthesia in 60 patients undergoing ambulatory surgery. METHODS: Patients were allocated randomly to receive remifentanil to a target blood concentration of 2 ng ml(-1) (low), 4 ng ml(-1) (medium), or 8 ng ml(-1) (high), administered by target-controlled infusion (TCI). After equilibration, propofol TCI was commenced in closed-loop control, with auditory evoked potentials (AEPex) as the input signal, aiming for an AEPex of 35. This was to ensure a comparable and unbiased level of anaesthesia in all patients. RESULTS: We found a dose-dependent decrease in propofol requirements with increasing remifentanil concentrations. The mean (95% CI) propofol target blood concentration during adequate anaesthesia was 4.96 (3.85-6.01) micro g ml(-1) in the low, 3.46 (2.96-3.96) micro g ml(-1) in the medium, and 3.01 (2.20-3.38) micro g ml(-1) in the high group. There was no significant difference when recovery end points were achieved between the groups. Cardiovascular changes were moderate, but most pronounced in the high concentration group, with a decrease in heart rate of 21% compared with baseline. The mean calculated effect site propofol concentration at loss of consciousness was 2.08 (1.85-2.32) micro g ml(-1), and at recovery of consciousness was 1.85 (1.68-2.00) micro g ml(-1). CONCLUSIONS: This study confirms a synergistic interaction between remifentanil and propofol during surgery, whereas the contribution of remifentanil in the absence of stimulation seems limited. In addition, our results suggest that the propofol effect site concentration provides a guide to the value at which the patient recovers consciousness.

Adolescent↗

Bispectral index, serum drug concentrations and emergence associated with individually adjusted target-controlled infusions of remifentanil and propofol for laparoscopic surgery.

BACKGROUND: Target-controlled infusions (TCI) are used to simplify administration and increase precision of i.v. drugs during general anaesthesia. However, there is a limited relationship between preset targets and measured concentrations of drugs and between measured concentrations and measures of brain function, such as the bispectral index (BIS). METHODS: We set out to evaluate the performance of TCI devices for propofol (Diprifusor) and remifentanil (Remifusor, prototype), during laparoscopic cholecystectomy in 21 patients. We also checked if there was any correlation between serum concentrations of propofol and BIS during individually adjusted anaesthesia. RESULTS: The Diprifusor and Remifusor had a median absolute performance error of 60% and 25% respectively. Propofol concentrations were underpredicted by a median of 60%, and remifentanil concentrations were slightly overpredicted by a median of 7%. When anaesthesia was adjusted to keep BIS values between 45 and 60, no correlation existed between measured concentrations of propofol and the corresponding BIS values, although both BIS and serum propofol concentration discriminated well between the awake and asleep states. Emergence was rapid and uneventful in all patients. Female patients had a more rapid emergence than male patients (6.6 and 11.6 min respectively). CONCLUSIONS: TCI devices for remifentanil and propofol result in large variation in measured serum concentrations. The lack of correlation between BIS and serum concentrations of propofol adds to the debate about whether BIS measures hypnosis as a graded state during surgery. This study confirms that women wake up faster than men, but provides no explanation for this repeatedly shown difference.

Adult↗

Predicted values of propofol EC50 and sevoflurane concentration for insertion of laryngeal mask Classic and ProSeal.

BACKGROUND: A new laryngeal mask airway, the ProSeal (PLMA), is said to be more difficult to insert than the laryngeal mask airway Classic (CLMA) using propofol anaesthesia. Therefore, we expected a greater dose of propofol and sevoflurane to be required to insert the PLMA compared with the CLMA. We determined the effective concentration 50% (EC(50)) of propofol and end-tidal sevoflurane to allow insertion of the PLMA and the CLMA. METHODS: Seventy-six elective female patients (aged 20-60 yr and ASA I-II) were randomly assigned to one of four groups. Either a PLMA or a CLMA was inserted using either propofol target controlled infusion or sevoflurane. Both propofol and sevoflurane targets were determined with a modified Dixon's up-and-down method. After equilibration between the predetermined blood and effect site concentrations, which had been held steady for more than 10 min, LMA insertion was attempted without neuromuscular block. RESULTS: The predicted EC(50CLMA) and EC(50PLMA) for propofol were 3.14 (0.33) and 4.32 (0.67) micro g ml(-1). E'(CLMA) and E'(PLMA) of sevoflurane (mean (SD)) were 2.36 (0.22) and 2.82 (0.45)% (P<0.01 and 0.05, respectively). CONCLUSIONS: The estimated concentration of propofol and the sevoflurane concentration needed to allow insertion of the ProSeal are respectively 38 and 20% greater than those needed for insertion of the Classic LMA.

Adult↗

Chronic ethanol consumption does not affect action of propofol on rat hippocampal acetylcholine release in vivo.

BACKGROUND: The aim of this study was to examine ethanol-consumption-related changes in the effects of propofol on rat hippocampal acetylcholine (ACh) release. METHODS: Male Sprague-Dawley rats received a solution of ethanol (20% v/v) for 24 weeks while controls received tap water. The effects of propofol were examined by in vivo microdialysis, with ACh release from the hippocampal regions determined by high-performance liquid chromatography with electrochemical detection (HPLC-ECD). RESULTS: Propofol 50 mg kg(-1) i.p. significantly decreased basal hippocampal ACh release in ethanol-treated and control rats by 50.4 (sem 4.7)% and 38.3 (11.1)%, respectively. Propofol 100 mg kg(-1) i.p. significantly decreased basal hippocampal ACh release in ethanol-treated and control rats by 67.5 (3.7)% and 55.9 (7.4)%, respectively. The reduction in hippocampal ACh release induced by 50 or 100 mg kg(-1) i.p. propofol was not significantly different between ethanol-treated and control rats. There was no significant difference in the duration of sleep between the two groups. CONCLUSIONS: These results demonstrate that chronic ethanol consumption does not augment the inhibitory actions of propofol on rat hippocampal ACh release. These findings appear to be inconsistent with the notion that chronic ethanol intake enhances the propofol-induced inhibition of the hippocampal cholinergic system and related mental dysfunction.

Acetylcholine↗

Assessment of the cough reflex after propofol anaesthesia for colonoscopy.

BACKGROUND: Dysfunction of the cough reflex as a result of the lingering effects of anaesthetics may lead to aspiration pneumonia or retained secretions after general anaesthesia. It is unknown whether low concentrations of propofol alter the cough reflex in the early period after anaesthesia. The objective of this study was to investigate the effect of low concentrations of propofol on the cough reflex sensitivity as assessed by the cough reflex threshold to an inhaled irritant. METHODS: Fifteen, ASA I-II, non-smoking patients undergoing elective colonoscopy were studied. Anaesthesia was induced and maintained with a blood target-controlled propofol infusion. Cough reflex threshold was measured with citric acid. Increasing concentrations of nebulized citric acid (2.5, 5, 10, 20, 40, 80, 160, 320, and 640 mg ml(-1)) were delivered during inspiration until a cough was evoked. The citric acid concentration eliciting one cough (C1) was defined as the cough reflex threshold. C1 was log transformed for statistical analysis (Log C1). Log C1 was measured before anaesthesia and during the recovery period with estimated decreasing propofol concentrations of 1.2, 0.9, 0.6, and 0.3 microg ml(-1). RESULTS: Log C1 (median; interquartile range) measured with propofol concentrations of 1.2, 0.9, 0.6, 0.3, and 0 microg ml(-1) were 1.9 (0.6), 1.9 (1.0), 1.9 (1.1), 1.9 (0.6), and 1.9 (0.7) mg ml(-1) (NS), respectively. However, light sedation was observed with propofol concentrations of 1.2 and 0.9 microg ml(-1). CONCLUSION: This study indicates that residual sedation after propofol anaesthesia for colonoscopy does not adversely affect the cough reflex.

Adult↗

Development of acute tolerance to the EEG effect of propofol in rats.

BACKGROUND: A previous study in rats with propofol suggested the development of acute tolerance to the EEG effect. The aim of this study was to evaluate acute tolerance by means of EEG-controlled closed-loop anaesthesia as this approach allows precise determination of drug requirement to maintain a defined drug effect. METHODS: Ten male Sprague-Dawley rats [weight 402 (40) g, mean (SD)] were included in the study. The EEG was recorded with occipito-occipital needle electrodes and a modified median frequency (mMEF) of the EEG power spectrum was used as a pharmacodynamic control parameter. The propofol infusion rate was controlled by a model-based adaptive algorithm to maintain a set point of mMEF=3 (0.5) Hz for 90 min. The performance of the closed-loop system was characterized by the prediction error PE=(mMEF-set point)/set point. Plasma propofol concentrations were determined from arterial samples by HPLC. RESULTS: The chosen set point was successfully maintained in all rats. The median (SE) and absolute median values of PE were -5.0 (0.3) and 11.3 (0.2)% respectively. Propofol concentration increased significantly from 2.9 (2.2) microg ml(-1) at the beginning to 5.8 (3.8) microg ml(-1) at 90 min [mean (SD), P<0.05]. The cumulative dose increased linearly, with a mean infusion rate of 0.60 (0.16) mg kg(-1) min(-1). The minimum value of the mean arterial pressure during closed-loop administration of propofol was 130 (24) mm Hg, compared with a baseline value of 141 (12) mm Hg. CONCLUSIONS: The increase in propofol concentration at constant EEG effect indicates development of acute tolerance to the hypnotic effect of propofol.

Anesthetics, Intravenous↗

Halothane and propofol differentially affect electroencephalographic responses to noxious stimulation.

BACKGROUND: Anaesthetics blunt neuronal responses to noxious stimulation, including effects on electroencephalographic (EEG) responses. It is unclear how anaesthetics differ in their ability to modulate noxious stimulation-evoked EEG activation. We investigated the actions of propofol and halothane on EEG responses to noxious stimuli, including repetitive electrical C-fibre stimulation, which normally evokes neuronal wind-up. METHODS: Rats were anaesthetized with halothane (n=8) or propofol (n=8), at 0.8x or 1.2x the amount required to produce immobility in response to tail clamping [minimum alveolar concentration (MAC) for halothane and median effective dose (ED(50)) for propofol]. We recorded EEG responses to repetitive electrical stimulus trains (delivered to the tail at 0.1, 1 and 3 Hz) as well as supramaximal noxious tail stimulation (clamp; 50 Hz electrical stimulus, each for 30 s). RESULTS: Under halothane anaesthesia, noxious stimuli evoked an EEG activation response manifested by increased spectral edge frequency (SEF) and median edge frequency (MEF). At 0.8 MAC halothane, the tail clamp increased the MEF from approximately 6 to approximately 8.5 Hz, and the SEF from approximately 25.5 to approximately 27 Hz. At both 0.8 and 1.2 MAC halothane, similar patterns of EEG activation were observed with the 1 Hz, 3 Hz and tetanic stimulus trains, but not with 0.1 Hz stimulation, which does not evoke wind-up. Under propofol anaesthesia, noxious stimuli were generally ineffective in causing EEG activation. At 0.8 ED(50) propofol, only the tail clamp and 1 Hz stimuli increased MEF ( approximately 8 to approximately 10-10.5 Hz). At the higher propofol infusion rate (1.2 ED(50)) the repetitive electrical stimuli did not evoke an EEG response, but the tetanic stimulus and the tail clamp paradoxically decreased SEF (from approximately 23 to approximately 21.5 Hz). CONCLUSIONS: Propofol has a more significant blunting effect on EEG responses to noxious stimulation compared with halothane.

Anesthetics, Inhalation↗

Cerebral haemodynamic changes during propofol-remifentanil or sevoflurane anaesthesia: transcranial Doppler study under bispectral index monitoring.

BACKGROUND: Sevoflurane or propofol-remifentanil-based anaesthetic regimens represent modern techniques for neurosurgical anaesthesia. Nevertheless, there are potential differences related to their activity on the cerebrovascular system. The magnitude of such difference is not completely known. METHODS: In total 40 patients, treated for spinal or maxillo-facial disorders, were randomly allocated to either i.v. propofol-remifentanil or inhalational sevoflurane anaesthesia. Transcranial Doppler was used to assess changes in cerebral blood flow velocity, carbon dioxide reactivity, cerebral autoregulation and the bispectral index to assess the depth of anaesthesia. RESULTS: Time-averaged mean flow velocity (MFV) was significantly reduced after induction of anaesthesia in both sevoflurane and propofol-remifentanil groups (P<0.001). At deeper levels of anaesthesia, MFV increased in the sevoflurane group, suggesting an uncoupling flow/metabolism, whereas it was further reduced in the propofol-remifentanil group (P<0.001). Indices of cerebral autoregulation were reduced in patients with high-dose sevoflurane whereas autoregulation was preserved in patients anaesthetized with propofol-remifentanil (P<0.001). Higher CO(2) concentrations impaired cerebral autoregulation in the sevoflurane group but not in patients anaesthetized with propofol-remifentanil. CONCLUSIONS: Propofol-remifentanil anaesthesia induced a dose-dependent low-flow state with preserved cerebral autoregulation, whereas sevoflurane at high doses provided a certain degree of luxury perfusion.

Adult↗

Predictive performance of 'Servin's formula' during BIS-guided propofol-remifentanil target-controlled infusion in morbidly obese patients.

BACKGROUND: The aim of this study was to assess the predictive performance of 'Servin's formula' for bispectral index (BIS)-guided propofol-remifentanil target-controlled infusion (TCI) in morbidly obese patients. METHODS: Twenty patients (ASA physical status II-III, age 32-64 yr) undergoing bilio-intestinal bypass surgery, were recruited. Anaesthesia was induced by using a TCI of propofol with an initial target plasma concentration of 6 microg ml(-1), then adapted to maintain stable BIS values ranging between 40 and 50. A TCI of remifentanil was added to achieve pain control and haemodynamic stability. For propofol, weight was corrected as suggested by Servin and colleagues. With ideal body weight (IBW) corrected according to formula suggested by Lemmens and colleagues. For remifentanil, weight was corrected according to IBW. Arterial blood samples for the determination of blood propofol concentrations were collected at different surgical times. The predictive performance of propofol TCI was evaluated by examining performance accuracy. RESULTS: Median prediction error and median absolute prediction error were -32.6% (range -53.4%; -2.5%) and 33.1% (10.8%; 53.4%), respectively. Wobble median value was 5.9% (2.5%; 25.2%) while divergence median value was -1.5% h(-1) (-7.7; 33.8% h(-1)). CONCLUSION: Significant bias between predicted and measured plasma propofol concentrations was found while the low wobble values suggest that propofol TCI system is able to maintain stable drug concentrations over time. As already suggested before, a computer simulation confirmed that the TCI system performance could be significantly improved when total body weight is used.

Adult↗

An evaluation of propofol toxicity on mouse oocytes and preimplantation embryos.

Mouse biological assays were used to investigate potential adverse effects of propofol on the oocyte's competence to fuse with spermatozoa and on the embryo's ability to develop to the blastocyst stage. Cumulus-enclosed metaphase II oocytes were exposed for 1 h to 0.01, 0.1, 0.4, 1 and 10 microg/ml propofol (Diprivan) and subjected to a sperm-oocyte fusion test based on the dye (Hoechst 33342) transfer technique. Oocytes exposed to 0.4, 1 and 10 microg/ml propofol showed a significant reduction in the rate of sperm fusion and underwent pronuclei formation at a rate similar to that of sperm fusion. In a second trial, mouse 1-cell and 2-cell embryos were exposed to varying propofol concentrations for 14h and then checked for subsequent development. Although adverse effects were not observed in 2-cell embryos, treatment of 1-cell embryos with propofol concentrations ranging from 0.01 to 10 microg/ml resulted in the inhibition of cleavage to blastocyst stage. We conclude that propofol can negatively influence fertilization in the mouse by impairing the oocyte's ability to fuse with spermatozoa, without interfering with the sperm-induced activation of the cell cycle. Moreover, we document the peculiar sensitivity to propofol of mouse 1-cell embryos as compared with 2-cell embryos.

Anesthetics, Intravenous↗

Hemodynamic changes during induction of anesthesia with eltanolone and propofol in dogs.

The purpose of this study was to examine global and regional hemodynamic changes during induction of anesthesia with eltanolone, a new short-acting steroid hypnotic, as compared to propofol, in chronically instrumented dogs. The effects on cardiac performance were assessed in six animals. Renal and hepatic blood flows were examined in a separate study including five animals. Two doses of each drug were investigated: eltanolone 2.5 and 5 mg/kg and propofol 7.5 and 15 mg/kg. Left atrial filling pressures and cardiac output were not affected by either drug. Maximum rate of increase of left ventricular pressures decreased both with eltanolone (-28% and -40% from awake control for the 2.5 and 5 mg/kg doses, respectively) and with propofol (-19% and -30% from awake controls with 7.5 and 15 mg/kg respectively). In contrast to propofol, eltanolone preserved arterial blood pressure. Propofol lowered systemic vascular resistance (-21% and -39% with the low and high dose, respectively), and only slightly decreased left ventricular wall thickening fraction (-16% and -21%). Eltanolone did not affect systemic vascular resistance but reduced the wall-thickening fraction dose-dependently (-28% and -61%). Propofol, but not eltanolone, induced moderate coronary vasodilation. Hepatic arterial blood flow velocity decreased dose-dependently (-21% and -64%) during eltanolone anesthesia whereas, in contrast, it increased after propofol (+59% and +64%). Renal and portal venous blood flows remained essentially unaltered from awake conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Intravenous↗