Differential Effects Of Propofol Research Articles

Differential effects of propofol and ketamine on critical brain dynamics.

Whether the brain operates at a critical "tipping" point is a long standing scientific question, with evidence from both cellular and systems-scale studies suggesting that the brain does sit in, or near, a critical regime. Neuroimaging studies of humans in altered states of consciousness have prompted the suggestion that maintenance of critical dynamics is necessary for the emergence of consciousness and complex cognition, and that reduced or disorganized consciousness may be associated with deviations from criticality. Unfortunately, many of the cellular-level studies reporting signs of criticality were performed in non-conscious systems (in vitro neuronal cultures) or unconscious animals (e.g. anaesthetized rats). Here we attempted to address this knowledge gap by exploring critical brain dynamics in invasive ECoG recordings from multiple sessions with a single macaque as the animal transitioned from consciousness to unconsciousness under different anaesthetics (ketamine and propofol). We use a previously-validated test of criticality: avalanche dynamics to assess the differences in brain dynamics between normal consciousness and both drug-states. Propofol and ketamine were selected due to their differential effects on consciousness (ketamine, but not propofol, is known to induce an unusual state known as "dissociative anaesthesia"). Our analyses indicate that propofol dramatically restricted the size and duration of avalanches, while ketamine allowed for more awake-like dynamics to persist. In addition, propofol, but not ketamine, triggered a large reduction in the complexity of brain dynamics. All states, however, showed some signs of persistent criticality when testing for exponent relations and universal shape-collapse. Further, maintenance of critical brain dynamics may be important for regulation and control of conscious awareness.

Differential effects of propofol and dexmedetomidine on neuroinflammation induced by systemic endotoxin lipopolysaccharides in adult mice

Propofol and dexmedetomidine are commonly used in clinical situations where neuroinflammation may be imminent or even established but comparative data on their effects on neuroinflammatory and cognitive parameters are lacking. Using a murine model of neuroinflammation induced by systemic lipopolysaccharide (LPS), this study compared the effects of these two agents on cognitive function, neuroinflammatory parameters, oxidative stress and neurotransmission. Male adult C57BL/6 N mice were anaesthetised with propofol or dexmedetomidine prior to intraperitoneal injection of LPS. Cognitive and motor function were assessed by the Y-maze and Rotarod tests respectively. Inflammatory responses were evaluated by relative levels of cytokine mRNA and immunoreactivity of glia cells. LPS caused a marked elevation in IL-1β and TNF-α levels both peripherally and in the brain, together with microglia activation (p < 0.05) and cognitive impairment. These changes were accompanied by an increase in 8-hydroxy-2′-deoxyguanosine (8−OHdG) (p < 0.05). Dexmedetomidine attenuated microglia activation (p < 0.05) and the elevation in 8−OHdG level (p < 0.05). Propofol did not affect cognition. However, both drugs lowered the number of vesicular glutamate transporter 1 (VGLUT 1), but was associated with higher levels of apoptosis and 8−OHdG (p < 0.05). Data from this study suggest dexmedetomidine and propofol have different anti-neuroinflammatory and neuroprotective profiles. However, neither drug can fully attenuate the effects of LPS induced cognitive impairment.

Effect of Continuous Propofol Infusion in Rat on Tau Phosphorylation with or without Temperature Control.

Several studies suggest a relationship between anesthesia-induced tau hyperphosphorylation and the development of postoperative cognitive dysfunction. This study further characterized the effects of continuous propofol infusion on tau protein phosphorylation in rats, with or without temperature control. Propofol was administered intravenously to 8-10-week-old male Sprague-Dawley rats and infused to the loss of the righting reflex for 2 h continuously. Proteins from cortex and hippocampus were examined by western blot and immunohistochemistry. Rectal temperature was significantly decreased during propofol infusion. Propofol with hypothermia significantly increased phosphorylation of tau at AT8, AT180, Thr205, and Ser199 in cortex and hippocampus except Ser396. With temperature maintenance, propofol still induced significant elevation of AT8, Thr205, and Ser199 in cortex and hippocampus; however, increase of AT180 and Ser396 was only found in hippocampus and cortex, respectively. Differential effects of propofol with or without hypothermia on multiple tau related kinases, such as Akt/GSK3β, MAPK pathways, or phosphatase (PP2A), were demonstrated in region-specific manner. These findings indicated that propofol increased tau phosphorylation under both normothermic and hypothermic conditions, and temperature control could partially attenuate the hyperphosphorylation of tau. Further studies are warranted to determine the long-term impact of propofol on the tau pathology and cognitive functions.

Differential effects of propofol and isoflurane on the relationship between EEG Narcotrend index and clinical stages of anaesthetic depth in sheep undergoing experimental cardiac surgery

The electroencephalogram (EEG) Narcotrend index (NI) has been shown to improve anaesthetic depth monitoring in isoflurane-anaesthetised sheep. Data obtained from 13 anaesthetised juvenile female sheep were analysed retrospectively in order to assess the relationship between clinical stages of anaesthesia (CS) and NI during both propofol and isoflurane anaesthesia. Polynomial regression analysis revealed no significant association between CS and NI for propofol (R = 0.374, R2 = 0.140, P = 0.403) but for isoflurane anaesthesia (R = 0.548, R2 = 0.301, P = 0.010) there was a significant relationship. Furthermore, a strong correlation existed between end-tidal isoflurane concentration (ISOET) and CS (r = −0.463, P = 0.008). A combination of assessment of clinical signs and analogous EEG patterns is recommended during propofol anaesthesia.

Differential effects of propofol and sevoflurane on QT interval during anesthetic induction

There have been conflicting reports on whether propofol prolongs, shortens, or does not change QT interval. The aim of this study was to determine the effect of target-controlled infusion (TCI) of propofol on heart rate-corrected QT (QTc) interval during anesthetic induction. We examined 50 patients undergoing lumbar spine surgery. Patients received 3 μg/kg of fentanyl and were randomly allocated to one of the following 2 groups. Group S patients received 5 mg/kg of thiamylal followed by sevoflurane, 5 % at the inhaled concentration. Group P patients received propofol using TCI system at 5 μg/mL for 2 min followed by 3 μg/mL. Tracheal intubation was performed after vecuronium administration. Heart rate (HR), mean arterial pressure (MAP), bispectral index score (BIS), and QTc interval in 12-lead electrocardiogram were recorded at the following time points: just before fentanyl administration (T1), 2 min after fentanyl injection (T2), 1 min after thiamylal injection or 2 min after the start of TCI (T3), just before intubation (T4), and 2 min after intubation (T5). BIS and MAP significantly decreased after anesthetic induction in both groups. HR decreased after anesthetic induction and recovered after tracheal intubation in group P, whereas it did changed in group S throughout the study period. QTc interval was shortened at T3 and T4 in group P, but prolonged at T3, T4, and T5 in group S, as compared with T1. Propofol TCI shortens QTc interval, whereas sevoflurane prolongs QTc interval during anesthetic induction.

Differential effects of propofol and isoflurane on glucose utilization and insulin secretion

AimsVolatile anesthetics, such as isoflurane, reverse glucose-induced inhibition of pancreatic adenosine triphosphate-sensitive potassium (KATP) channel activity, resulting in reduced insulin secretion and impaired glucose tolerance. No previous studies have investigated the effects of intravenous anesthetics, such as propofol, on pancreatic KATP channels. We investigated the cellular mechanisms underlying the effects of isoflurane and propofol on pancreatic KATP channels and insulin secretion. Main methodsIntravenous glucose tolerance tests (IVGTT) were performed on male rabbits. Pancreatic islets were isolated from male rats and used for a perifusion study, measurement of intracellular ATP concentration ([ATP]i), and patch clamp experiments. Key findingsGlucose stimulus significantly increased insulin secretion during propofol anesthesia, but not isoflurane anesthesia, in IVGTT study. In perifusion experiments, both islets exposed to propofol and control islets not exposed to anesthetic had a biphasic insulin secretory response to a high dose of glucose. However, isoflurane markedly inhibited glucose-induced insulin secretion. In a patch clamp study, the relationship between ATP concentration and channel activity could be fitted by the Hill equation with a half-maximal inhibition of 22.4, 15.8, and 218.8μM in the absence of anesthetic, and with propofol, and isoflurane, respectively. [ATP]i and single KATP channel conductance did not differ in islets exposed to isoflurane or propofol. SignificanceOur results indicate that isoflurane, but not propofol, decreases the ATP sensitivity of KATP channels and impairs glucose-stimulated insulin release. These differential actions of isoflurane and propofol on ATP sensitivity may explain the differential effects of isoflurane and propofol on insulin release.

Differential effects of propofol and isoflurane on the activation of T‐helper cells in lung cancer patients

It is suggested that activation and differentiation of T-helper cells are required for peri-operative anti-tumor and anti-infection immunity. The present study aimed to evaluate whether propofol stimulates the activation and differentiation of these cells in patients undergoing pulmonary lobectomy for non-small-cell lung cancer. Thirty patients were randomly allocated to receive propofol or isoflurane throughout surgery. The CD4(+)CD28(+) percentage (p < 0.0001) and the ratio of interferon-gamma:interleukin-4 (p = 0.001) all increased with propofol but showed no change with isoflurane. In contrast, cortisol increased with isoflurane (p < 0.0001) but not with propofol over time (p = 0.06). We conclude that propofol promotes activation and differentiation of peripheral T-helper cells.

Differential Effects of Propofol and Sevoflurane on Ischemia-induced Ventricular Arrhythmias and Phosphorylated Connexin 43 Protein in Rats

The effects of anesthetics on ischemia-induced ventricular arrhythmias remain poorly studied. This study investigated the effects of propofol and sevoflurane on the survival rate and morbidity as a result of ventricular arrhythmias, and defined a possible mechanism for the arrhythmogenic properties of anesthetics during acute myocardial ischemia. Under anesthesia with intraperitoneal sodium pentobarbital, Sprague-Dawley rats underwent 30 min of left anterior descending coronary artery ligation. The rats were divided into a low-dose propofol (Prop-LD) group (39 mg X kg(-1) X hr(-1), n = 18), a high-dose propofol group (78 mg x kg(-1) x hr(-1), n = 18), a sevoflurane group (2.5%, n = 18) and a control group (n = 18). The survival rate and morbidity as a result of ventricular arrhythmias were determined, and the amount of phosphorylated connexin 43 protein was measured 30 min after coronary artery ligation. The survival rate was 83% (15 of 18), 94% (17 of 18), 89% (16 of 18), and 67% (12 of 18, P = 0.038 vs. Prop-LD) in the control, Prop-LD, high-dose propofol, and sevoflurane groups, respectively. Sustained ventricular tachycardia was observed in 83% (15 of 18), 39% (7 of 18, P = 0.011 vs. control), 50% (9 of 18, P = 0.039 vs. control) and 94% (17 of 18, P < 0.01 vs. Prop-LD) in the control, Prop-LD, high-dose propofol, and sevoflurane groups, respectively. Immunoblotting showed a marked reduction in the amount of phosphorylated connexin 43 in the control and sevoflurane groups, as compared with the Prop-LD and high-dose propofol groups (P < 0.05). The authors' results suggest that propofol preserves connexin 43 phosphorylation during acute myocardial ischemia, as compared with sevoflurane, and this might protect the heart from serious ventricular arrhythmias during acute coronary occlusion.

Differential effects of propofol and ethanol on P2X4 receptors expressed in Xenopus oocytes

The current study investigated the effects of propofol on P2X4 receptors expressed in Xenopus oocytes using two-electrode voltage clamp. We also tested the effects of 100 mM ethanol on the same oocytes used to test propofol. Propofol potentiated ATP-gated currents in a concentration dependent manner in P2X4 receptors. In agreement with our previous findings, ethanol inhibited P2X4 receptors. The opposite effects of propofol and ethanol on P2X4 receptor function suggest that these anesthetics act via different sites/mechanisms in P2X receptors as has been suggested for GABAA and glycine receptors.

Differential effects of propofol on cerebrovascular carbon dioxide reactivity in elderly versus young subjects

Study Objective To examine the age-related difference between elderly and young patients in the effect of propofol on cerebrovascular carbon dioxide (CO 2) reactivity. Design Prospective controlled study. Setting University hospital. Patients Elderly (older than 70 years, n = 13) and young patients (younger than 25 years, n = 13) scheduled for elective orthopedic surgery. Interventions After induction of anesthesia, a 2.5-MHz pulsed transcranial Doppler probe was attached to the patient's head at the right temporal window, from which mean blood flow velocity of the middle cerebral artery was measured continuously. Measurements After obtaining baseline values of velocity of the middle cerebral artery, arterial blood gases, and cardiovascular hemodynamics, end-tidal CO 2 was decreased by increasing the ventilatory frequency by 2 to 5 breaths per minute. Measurements were repeated when end-tidal CO 2 decreased and remained stable for 5 to 10 minutes. Cerebrovascular CO 2 reactivity, at propofol doses of 5 and 10 mg/kg/h, was measured. Main Results No significant differences were observed between the 2 groups in baseline absolute and relative CO 2 reactivity. However, there were significant differences between the 2 groups in absolute or relative CO 2 reactivity at a propofol dosage of 5 mg/kg/h. (Absolute CO 2 reactivity in young patients: 2.1 ± 0.8 cm/s/mm Hg; elderly: 1.6 ± 0.4* cm/s/mm Hg. Relative CO 2 reactivity in young patients: 7.4% ± 1.6%/mm Hg; in the elderly: 6.5% ± 0.9%*/mm Hg; unpaired t test, * P < .05). In contrast, there were no significant differences between the 2 groups in terms of absolute or relative CO 2 reactivity at a propofol dosage of 10 mg/kg/h. Conclusions Cerebrovascular CO 2 reactivity in elderly patients was lower than that in young patients at a propofol dosage of 5 mg/kg/h.

Differential effects of propofol, ketamine, and thiopental anaesthesia on the skeletal muscle microcirculation of normotensive and hypertensive rats in vivo

This study utilized the dorsal microcirculatory chamber (DMC) model to determine differential effects of i.v. propofol, ketamine, and thiopental anaesthesia on the skeletal muscle microcirculation (10-180 micro m) of normotensive (Male Wistar Kyoto, WKY) and hypertensive (spontaneously hypertensive Harlan, SHR) rats, importantly, comparing responses to a conscious baseline. Three weeks following implantation of the DMC in WKY (n=8) and SHR (n=6) (130 g) 0.25 ml 100 g(-1) FITC-BSA (i.v.) was administered and the microcirculation viewed using fluorescent in vivo microscopy for a 30 min baseline (t=0-30 min). This was followed by either propofol, thiopental, ketamine, or saline (i.v. bolus induction over 5 min (t=30-35 min)), then maintenance step-up infusion for 60 min (t=45-105 min), so that animals received all four agents 1 week apart (56 experiments). Dilation of A3 arterioles (15-30 micro m) and V3 venules (20-40 microm) with propofol was greater in SHR (t=95 min, A3 36.7 (12)%, V3 15.5 (2.3)%) than WKY (t=95 min, A3 19.4 (7.4)%, V3 8.0 (2.3)%) (P<0.05). Constriction of A3 with ketamine was greater in SHR (t=95 min, A3 -29.1 (6.4)%) than WKY (A3 -17.5 (8.8)%) (P<0.05). This was accompanied by hypotension with propofol in SHR (-32% decrease in systolic arterial pressure), but not WKY (-6%) and hypertension with ketamine in WKY (-15%) and SHR (-24%) (P<0.05). During thiopental anaesthesia there was dilation of A1 (80-180 microm), A3, and V3 in WKY (P<0.05). Conversely, in SHR dilation of venules (29.2 (8.7)%) was accompanied by constriction of A1 and A3 (t=95 min, A1 -25.1 (5.9)%, A3-45.2 (3.1)%) (P<0.05). Within the skeletal muscle microcirculation of hypertensive rats there is enhanced dilation with propofol and constriction with ketamine, associated with exaggerated changes in arterial pressure. Thus, dysfunctional control mechanisms at the level of the microcirculation alter responses to anaesthesia during hypertension.

P–522 - Differential effects of propofol on recombinant P2X receptors expressed in HEK293 cells

P–522 - Differential effects of propofol on recombinant P2X receptors expressed in HEK293 cells

Differential effects of propofol, thiamylal and ketamine on the cricothyroid and posterior cricoarytenoid muscles of the canine larynx

To measure the electromyographic (EMG) responses of the phasic discharge in the cricothyroid (CT; a tensor muscle of the vocal folds) and the posterior cricoarytenoid (PCA; sole abductor muscle of the vocal folds) following intravenous infusion of propofol 1.0 mg.kg-1.min-1, thiamylal 1.0 mg.kg-1.min-1, or ketamine 0.5 mg.kg-1.min-1 for five minutes. Prospective, nonrandomized, controlled animal study. University research laboratory. Fifteen mongrel dogs, including three groups of five animals in each group. Under 0.2-0.3% halothane and oxygen anesthesia with spontaneous ventilation, phasic EMG activities of the CT and PCA muscles were recorded in an identical manner after the administration of each drug. Propofol infusion produced almost equal suppression of EMG activity of the CT and the PCA with time and three minutes after the start of infusion of propofol there was a significant depression of the phasic activities in the both muscles; EMG activity of the CT and the PCA was 33.8 +/- 21.2 and 36.6 +/- 22.9% (% of control, mean +/- SD) respectively P < 0.05). Thiamylal selectively reduced rhythmic discharges in the CT muscle during spontaneous breathing and significant depression of discharge in the CT muscle was observed three minutes after the drug (47.3 +/- 24.9%, P < 0.05). In contrast, both phasic EMG activities of the CT and the PCA were rhythmically active and the differential sensitivity between the CT and the PCA muscles was not observed after ketamine, even after ten minutes of administration. This study confirms a difference in sensitivity between the CT and the PCA muscles, demonstrating that the intrinsic laryngeal muscles do not behave similarly after the administration of conventional intravenous anaesthetic agents.

Differential effects of propofol and ketamine on cytosolic calcium concentrations of astrocytes in primary culture

Propofol has been shown recently to alter cellular communication mediated by gap junctions between astrocytes (a glial cell subpopulation involved in major brain functions). As marked increases in concentrations of cytosolic calcium ([Ca2+]i) produce closure of the gap junction, we have investigated the effects of both propofol and ketamine on resting [Ca2+]i concentrations in mouse cultured astrocytes using microfluorimetry with the indo-1 fluorescent probe. Propofol 10(-5) and 10(-4) mol litre-1 induced a monophasic transitory Ca2+ peak in a large subpopulation of the cells tested. This response exhibited characteristics close to those of the peak elicited by [L-Pro9] substance P (10(-7) mol litre-1), an activator of phospholipase C in astrocytes. In both cases, it possibly corresponded to mobilization of Ca2+ from endogenous stores. In a few cases, however, administration of propofol induced a moderate, but sustained increase in [Ca2+]i corresponding to the entry of external Ca2+ into the cells. In contrast, ketamine 10(-5) and 10(-4) mol litre-1 failed to affect [Ca2+]i resting concentrations. These findings indicate that clinically relevant concentrations of propofol, but not ketamine, increased [Ca2+]i concentration in astrocytes.

Differential Effects of Propofol and Enflurane on Contractions Dependent on Calcium Derived from the Sarcoplasmic Reticulum of Guinea Pig Isolated Papillary Muscles

We investigated the possibility that the effects of propofol on sarcoplasmic reticulum (SR) function may contribute to the myocardial depression induced by this anesthetic. With guinea pig isolated papillary muscles, the effects of propofol on transient alterations in contractility (termed "potentiated-state" contractions), after abrupt changes in stimulation frequency and brief periods of rest, were compared with those of enflurane and the inhibitor of SR function, ryanodine. These potentiated-state contractions are mediated by calcium derived largely from the SR. Propofol, enflurane, and ryanodine were applied at concentrations that produced approximately 50%-60% inhibition of "steady-state" contraction. Ryanodine abolished and enflurane attenuated the potentiated-state contractions, whereas propofol had no apparent effect. Although impairment of SR function may contribute to the depression of contractility induced by enflurane, propofol has no major effect on SR function.