Micro-fragmented fat injection reduces sepsis-induced acute inflammatory response in a mouse model.

BACKGROUND: Severe sepsis has a high mortality rate. There is increasing evidence that human mesenchymal stem cells possess immunomodulatory properties in sepsis, particularly those from adipose tissue. We hypothesised that micro-fragmented human fat, obtained with minimal alteration of the stromal vascular niche, attenuates the inflammatory response and improves outcome in a murine model of sepsis. METHODS: Micro-fragmented fat, lipoaspirate, or saline was administered intraperitoneally 2 h after caecal ligation and puncture (CLP) in C57Bl/6RJ ketamine-xylazine anaesthetised mice. The primary endpoint was the inflammatory score. Secondary endpoints included survival, physiological, histological, and biological parameters. RESULTS: In CLP mice, micro-fragmented fat administration significantly decreased the median (range) inflammatory score compared with saline [17 (14-20) vs 9 (8-12), P=0.006]. Secondary endpoints were also significantly improved in micro-fragmented fat-treated compared with saline-treated CLP mice. Improvement in inflammatory score and in survival was suppressed when micro-fragmented fat was co-administered with liposomes loaded with clodronate (macrophage toxin) or NS-398 (cyclo-oxygenase 2 inhibitor), but not with SC-560 (cyclo-oxygenase 1 inhibitor). CONCLUSIONS: In a murine model of severe sepsis, micro-fragmented fat improved early inflammatory status and outcome, at least in part, by a cyclo-oxygenase-2-mediated mechanism. The potential therapeutic value of micro-fragmented fat in severe sepsis warrants further investigation.

Mismatch negativity to predict subsequent awakening in deeply sedated critically ill patients.

BACKGROUND: Mismatch negativity (MMN) is the neurophysiological correlate of cognitive integration of novel stimuli. Although MMN is a well-established predictor of awakening in non-sedated comatose patients, its prognostic value in deeply sedated critically ill patients remains unknown. The aim of this prospective, observational pilot study was to investigate the prognostic value of MMN for subsequent awakening in deeply sedated critically ill patients. METHODS: MMN was recorded in 43 deeply sedated critically ill patients on Day 3 of ICU admission using a classical 'odd-ball' paradigm that delivers rare deviant sounds in a train of frequent standard sounds. Individual visual analyses and a group level analysis of recordings were performed. MMN amplitudes were then analysed according to the neurological status (awake vs not awake) at Day 28. RESULTS: Median (inter-quartile range) Richmond Assessment Sedation Scale (RASS) at the time of recording was -5 (range, from -5 to -4.5). Visual detection of MMN revealed a poor inter-rater agreement [kappa=0.17, 95% confidence interval (0.07-0.26)]. On Day 28, 30 (70%) patients had regained consciousness while 13 (30%) had not. Quantitative group level analysis revealed a significantly greater MMN amplitude for patients who awakened compared with those who had not [mean (standard deviation) = -0.65 (1.4) vs 0.08 (0.17) µV, respectively; P=0.003). CONCLUSIONS: MMN can be observed in deeply sedated critically ill patients and could help predict subsequent awakening. However, visual analysis alone is unreliable and should be systematically completed with individual level statistics.

Impact of sleep deprivation on anaesthesia residents' non-technical skills: a pilot simulation-based prospective randomized trial.

BACKGROUND: Sleep deprivation is common in anaesthesia residents, but its impact on performance remains uncertain. Non-technical skills (team working, situation awareness, decision making, and task management) are key components of quality of care in anaesthesia, particularly in crisis situations occurring in the operating room. The impact of sleep deprivation on non-technical skills is unknown. We tested the hypothesis that in anaesthesia residents sleep deprivation is associated with impaired non-technical skills. METHODS: Twenty anaesthesia residents were randomly allocated to undergo a simulation session after a night shift [sleep-deprived (SLD) group, n =10] or after a night of rest [rested (R) group, n =10] from January to March 2015. The simulated scenario was a situation of crisis management in the operating room. The primary end point was a composite score of anaesthetists' non-technical skills (ANTS) assessed by two blinded evaluators. RESULTS: Non-technical skills were significantly impaired in the SLD group [ANTS score 12.2 (interquartile range 10.5-13)] compared with the R group [14.5 (14-15), P <0.02]. This difference was mainly accounted for by a difference in the team working item. On the day of simulation, the SLD group showed increased sleepiness and decreased confidence in anaesthesia skills. CONCLUSIONS: In this randomized pilot trial, sleep deprivation was associated with impaired non-technical skills of anaesthesia residents in a simulated anaesthesia intraoperative crisis scenario. TRIAL REGISTRATION: NCT02622217.

Pilot study of closed-loop anaesthesia for liver transplantation.

BACKGROUND: Automated titration of propofol and remifentanil guided by the bispectral index (BIS) has been used for numerous surgical procedures. Orthotopic liver transplantation (OLT) uniquely combines major changes in circulating volume, an anhepatic phase, and ischaemia-reperfusion syndrome. We assessed the behaviour of this automated controller during OLT. METHODS: Adult patients undergoing OLT were included in this pilot study. Consumption of propofol and remifentanil was calculated for each surgery period (dissection, anhepatic, and liver reperfusion phases). Arterial blood samples were collected at several time points to allow comparison of actual with calculated propofol and remifentanil concentrations. Data are presented as median [25th and 75th percentiles] or percentage (95% confidence interval). RESULTS: Thirteen patients were studied. System performance, defined as the percentage of time with BIS in the range 40-60, was 88% (86-94) of the total duration of anaesthesia. Propofol requirement was decreased during the anhepatic phase compared with the dissection phase (2.9 [1.9-5.0] mg kg(-1) h(-1) and 4.6 [3.5-8.1] mg kg(-1) h(-1); P<0.03) while remifentanil consumption was unchanged (0.11 [0.09-0.19] µg kg- (1) min(-1)). Bland-Altman analysis showed a weak concordance for propofol (bias of 0.7 µg ml(-1) and limits of agreement of -2.2 to +3.7 µg ml(-1)) and remifentanil (bias of 1.3 ng ml(-1) and limits of agreement -4.3 to +6.8 ng ml(-1)). No adverse events were reported during anaesthesia. CONCLUSIONS: This pilot study indicates that automated titration of propofol and remifentanil guided by the BIS is feasible during OLT.

Limits of agreement between measures obtained from standard laboratory and the point-of-care device Hemochron Signature Elite(R) during acute haemorrhage.

BACKGROUND: Rapid diagnosis of coagulopathy in the bleeding patient using point-of-care (POC) devices would be ideal. The Hemochron Signature Elite(®) (HC(®)) is a POC device that determines international normalized ratio (INR) and activated partial thromboplastin time (aPTT). The aim of the study was to evaluate the agreement for INR and aPTT between the HC(®) and standard laboratory values in acute haemorrhage. METHODS: This was a single-centre observational prospective study including patients with acute haemorrhage. Laboratory INR and aPTT were compared with simultaneous measurements performed with the HC(®). The diagnostic performance of HC(®) was determined; bias and limits of agreement were calculated according to the method of Bland and Altman. RESULTS: Seventy-two pairs of measurements from 39 patients were analysed. The bias between the INR-HC(®) and aPTT-HC(®) measurements and the central laboratory were 0.02 and -1.13, respectively. The Spearman's correlation coefficients for the INR-HC(®)/INR-lab and the aPTT-HC(®)/aPTT-lab were 0.68 and -0.29, respectively. Twenty-seven per cent of INR-HC(®) values and 89% of the aPTT-HC(®) values exceeded the predefined limits of agreement. The INR-HC(®) measurement identified patients with a central laboratory INR >1.5 with a sensitivity, specificity, and positive and negative predictive values of 83%, 70%, 76%, and 77%, respectively. CONCLUSIONS: The results showed a lack of agreement between the INR-HC(®) and the aPTT-HC(®) measurements and the standard laboratory in the context of acute haemorrhage. The INR-HC(®) showed moderate performance as a decision-making tool to detect coagulopathy in the context of acute haemorrhage.

Fatal Escherichia coli skin and soft tissue infections in liver transplant recipients: report of three cases.

Gram-negative bacilli are unusual agents of skin and soft tissue infections. Most previous cases have been reported in cirrhotic or immunocompromised patients, including a single case in a liver transplant recipient. The present report describes 3 cases of fatal skin or soft tissue infections caused by Escherichia coli that occurred in the postoperative course of liver transplantation. The 3 patients were profoundly immunosuppressed as a result of pre-transplant cirrhosis and the postoperative administration of a potent immunosuppressive therapy. Skin and soft tissue infections developed within the first week after liver transplantation, while graft liver function was satisfactory. The 3 patients presented with fever and skin lesions with or without bullae. Despite prompt appropriate antibiotic therapy and surgical debridement, the outcome was rapidly fatal (24 h on average). E. coli was isolated from subcutaneous tissues in 2 cases and from several blood cultures in the third one. The 3 isolates belonged to distinct phylogenetic groups, and did not harbor most of the virulence factors usually reported in extraintestinal pathogenic E. coli isolates. Our report suggests that E. coli can cause severe skin or soft tissue infection in the postoperative course of liver transplantation. The onset of infection is very early and the outcome is extremely poor, despite prompt adapted medical and surgical treatment. Host factors, rather than E. coli bacterial virulence potential, appear to be the major determinants of severity in these patients.

Deviation from a preoperative surgical and anaesthetic care plan is associated with increased risk of adverse intraoperative events in major abdominal surgery.

BACKGROUND: Perioperative coordination facilitates team communication and planning. The aim of this study was to determine how often deviation from predicted surgical conditions and a pre-established anaesthetic care plan in major abdominal surgery occurred, and whether this was associated with an increase in adverse clinical events. METHODS: In this prospective observational study, weekly preoperative interdisciplinary team meetings were conducted according to a joint care plan checklist in a tertiary care centre in France. Any discordance with preoperative predictions and deviation from the care plan were noted. A link to the incidence of predetermined adverse intraoperative events was investigated. RESULTS: Intraoperative adverse clinical events (ACEs) occurred in 15 % of all cases and were associated with postoperative complications [relative risk (RR) = 1.5; 95 % confidence interval (1.1; 2.2)]. Quality of prediction of surgical procedural items was modest, with one in five to six items not correctly predicted. Discordant surgical prediction was associated with an increased incidence of ACE. Deviation from the anaesthetic care plan occurred in around 13 %, which was more frequent when surgical prediction was inaccurate (RR > 3) and independently associated with ACE (odds ratio 6). CONCLUSION: Surgery was more difficult than expected in up to one out of five cases. In a similar proportion, disagreement between preoperative care plans and observed clinical management was independently associated with an increased risk of adverse clinical events.

Effect of age on the comparability of bispectral and state entropy indices during the maintenance of propofol-sufentanil anaesthesia.

BACKGROUND: Manufacturers recommend maintaining anaesthesia at a bispectral index (BIS) or state entropy (SE) index value between 40 and 60. METHODS: We prospectively studied 102 patients receiving propofol-sufentanil anaesthesia administered by anaesthetists blinded to these indices. The main endpoint was crude agreement (P(0)), defined as the proportion of agreement between BIS and SE index among three categories: <40, between 40 and 60, and >60. Discrepancies in recommendation (DR) were also considered. A DR is type 1 if BIS or SE is <40, while the other is simultaneously >60. A DR is type 2 when BIS and SE index values are on different sides of a threshold (40 or 60) with three subtypes according to the magnitude of their difference. A linear multiple regression was performed to identify covariates that are independently associated with P(0). RESULTS: In total, 12 147 pairs of values were studied. P(0) was 59.9 (24.5%) [mean (sd)]. Thirty-three patients presented more than 50% discordant pairs and only seven patients presented more than 95% concordant pairs. Type 1 DR occurred in only 1.1% of all the pairs. The median (inter-quartile range) number of type 2 DR varied from 5 (3-8) to 2 (1-3) according to the degree of difference. Multivariate analysis showed that age (P=0.0004) and electrode position (P=0.0084) were independently associated with P(0). An increase in the age of 10 yr decreases P(0) by 5%. CONCLUSIONS: The agreement between BIS and SE indices is moderate and deteriorates as patients' age increases. This study cannot determine which index is best adapted for elderly patients. Additional work comparing both indices with raw EEG traces is warranted.

Microbiological findings of culture-positive preservation fluid in liver transplantation.

Bacterial and fungal infections are the leading cause of mortality in liver transplant (LT) recipients. Few studies have examined the incidence of culture-positive preservation fluid (PF) and the outcome of related recipients. The aim of this study was to determine the incidence and the microbiologic findings of PF positive cultures, and to evaluate the impact on morbidity and mortality of LT recipients. A retrospective analysis of PF cultures performed after 477 LTs from cadaveric grafts between January 2001 and February 2008 was conducted. Forty-five (9.5%) PFs were found to be positive with 1 or 2 pathogens. The demographic profiles of recipients of PF with positive or negative cultures were similar. Enterobacteriaceae species were the most frequent organisms (n = 30), followed by Staphylococcus aureus (n = 5), coagulase-negative staphylococci (n = 5), enterococci (n = 4), and yeasts (n = 3). Mortality rate at 1 month was not significantly different in recipients with positive or sterile PF cultures (88.1% vs. 87.7%, respectively). The rate of bacteremia among LT recipients with positive or negative PF cultures was not statistically different. Systemic infections caused by the pathogen cultured from the PF occurred in 8 (18%) of the 45 recipients, including bacteremia (4/8) or intra-abdominal sepsis (5/8). Causative organisms were Enterobacteriaceae species (n = 5), Candida species (n = 2), and Enterococcus faecium (n = 1). Among the 8 patients who developed infection with the PF organism, 4 (50%) died in the intensive care unit (ICU) vs. an ICU mortality rate of 8% (3/37) in those who did not develop infection with the PF organism (P < 0.05). Infection occurred less frequently in recipients who received antimicrobial therapy with activity against the PF isolate than in those without appropriate treatment (41% vs. 3.8%, P < 0.005). Those who develop infection with organisms recovered from PF cultures appear to have high early mortality rates; therefore, appropriate antimicrobial therapy against organisms cultured from PF should be given.

Impact of preoperative maintenance or interruption of aspirin on thrombotic and bleeding events after elective non-cardiac surgery: the multicentre, randomized, blinded, placebo-controlled, STRATAGEM trial.

BACKGROUND: Patients receiving anti-platelet agents for secondary cardiovascular prevention frequently require non-cardiac surgery. A substantial proportion of these patients have their anti-platelet drug discontinued before operation; however, there is uncertainty about the impact of this practice. The aim of this study was to compare the effect of maintenance or interruption of aspirin before surgery, in terms of major thrombotic and bleeding events. METHODS: Patients treated with anti-platelet agents for secondary prevention and undergoing intermediate- or high-risk non-cardiac surgery were included in this multicentre, randomized, placebo-controlled, trial. We substituted non-aspirin anti-platelets with aspirin (75 mg daily) or placebo starting 10 days before surgery. The primary outcome was a composite score evaluating both major thrombotic and bleeding adverse events occurring within the first 30 postoperative days weighted by their severity (weights were established a priori using a Delphi consensus process). Analyses followed the intention-to-treat principle. RESULTS: We randomized 291 patients (n=145, aspirin group, and n=146, placebo group). The most frequent surgical procedures were orthopaedic surgery (52.2%), abdominal surgery (20.6%), and urologic surgery (15.5%). No significant difference was observed neither in the primary outcome score [mean values (SD)=0.67 (2.05) in the aspirin group vs 0.65 (2.04) in the placebo group, P=0.94] nor at day 30 in the number of major complications between groups. CONCLUSIONS: In these at-risk patients undergoing elective non-cardiac surgery, we did not find any difference in terms of occurrence of major thrombotic or bleeding events between preoperative maintenance or interruption of aspirin.

Age-adapted morphine titration produces equivalent analgesia and adverse effects in younger and older patients.

BACKGROUND: To determine the efficacy and safety of intravenous postoperative morphine titration in the elderly compared with younger patients. METHODS: In the post-anaesthesia care unit, patients complaining of pain received morphine until adequate pain relief. Intravenous morphine was titrated as 3 mg boluses in young (age 65 yr) and 2 mg in elderly patients (>65 yr) every 5 min. RESULTS: We studied 350 young and 68 elderly patients. There were no significant differences between the two age groups for pain intensity at the onset of titration (numerical rating scale, 7.4 +/- 1.7 in young vs. 7.5 +/- 1.7 in elderly patients), area under the curve of numerical rating scale vs. morphine boluses (97.7 +/- 59.6 vs. 98.2 +/- 62), number of boluses required to obtain pain relief (3 +/- 1.3 vs. 3 +/- 1.3), percentage of titration failures (10% vs. 9%) and incidence of excessive sedation (18% vs. 21%). Renal clearance was significantly reduced in elderly compared with young patients (55 +/- 21 vs. 85 +/- 15 mL min(-1); P < 0.0001). CONCLUSION: Using lower bolus doses, pain relief in the immediate postoperative period with morphine was as efficacious and safe in elderly patients as in younger patients. The decrease in renal clearance of morphine in the elderly justifies the reduction of intravenous morphine boluses for the treatment of postoperative pain.

[Delayed presentation of eclampsia: lessons from a case diagnosed at Day 11]. / Eclampsie retardée: leçons à tirer d'un cas survenu à j11 post-partum.

We report a case of late postpartum eclampsia at Day 11 in a 40-year-old woman after normal pregnancy and delivery. The delayed eclamptic episode is defined by seizures between two days and four weeks after delivery. About 40% of late eclampsia has no premonitory symptoms. This case highlights the possible diagnosis of late eclampsia even after normal pregnancy and delivery. Active and prompt management, brain imaging are mandating in cases of persistent headaches in postpartum.

Cough reflex sensitivity after elective Caesarean section under spinal anaesthesia and after vaginal delivery.

BACKGROUND: In pregnancy, airway oedema and heartburn may increase cough sensitivity, whereas spinal anaesthesia (SA) with local anaesthetics and opiates may decrease it. Decreased cough sensitivity increases the risk for pneumonia or retained secretions. The aim of this study was to determine whether cough sensitivity is increased in pregnant patients and if it is decreased after planned Caesarean section (CS) under SA. METHODS: Twenty-seven non-pregnant volunteers, 27 patients after vaginal delivery (VD group), and 28 patients after CS under SA (CS group) were studied. For SA, hyperbaric bupivacaine 8-12 mg, sufentanil 5 microg, and morphine 100 microg was given. Increasing concentrations of nebulized citric acid were delivered until eliciting cough. The concentration eliciting one (C1) and two coughs (C2) were recorded and log transformed for analysis (log C1 and log C2). RESULTS: Median (inter-quartile) log C1 was 1.3 (0.6) mg ml(-1) in the VD group, 1.6 (0.6) mg ml(-1) in the non-pregnant group (P < 0.01 vs VD group), and 2.2 (0.7) mg ml(-1) in the CS group (P < 0.0001 and P < 0.01 vs VD and non-pregnant groups, respectively). Similar results were observed with log C2. In CS group, log C1 and log C2 remained increased up to 4 h after SA. CONCLUSIONS: Cough sensitivity was increased after VD but decreased for up to 4 h after SA.

Sevoflurane preconditioning at 1 MAC only provides limited protection in patients undergoing coronary artery bypass surgery: a randomized bi-centre trial.

BACKGROUND: Volatile agents can mimic ischaemic preconditioning leading to a decrease in myocardial infarct size. The present study investigated if a 15 min sevoflurane administration before cardiopulmonary bypass (CPB) has a cardioprotective effect in patients undergoing coronary surgery. METHODS: Seventy-two patients were randomized in two centres. The intervention group (S) received 1 MAC sevoflurane administrated via the ventilator for 15 min followed by a 15 min washout before CPB, the control group did not. The primary outcome was the postoperative troponin Ic peak. A biopsy of the atrium was taken during canulation for enzyme dosages. Results are expressed as mean (SD). RESULTS: Neither troponin Ic nor tissular enzyme measurement exhibited any difference between the groups: peak of troponin Ic was 4.4 (5.6) in S group vs 5.2 (6.6) ng ml(-1) in control group (ns). Intratissular ecto-5'-nucleotidase activity was 7.1 (4.3) vs 8.5 (11.9), protein kinase C activity was 27.1 (15.7) vs 29.2 (28.7), tyrosine kinase activity was 101 (54.1) vs 98.5 (63.3), and P38 MAPKinase activity was 131.1 (76.1) vs 127.1 (86.8) nmol mg protein(-1) min(-1) in S group and control group, respectively (ns). However there were fewer patients with low postoperative cardiac index in S group (11% in S vs 35% in control group, P < 0.05) when considering the per protocol population. In S group, 25% of patients required an inotropic support during the postoperative period, vs 36% of patients in control group (ns). CONCLUSIONS: This study did not show a significant preconditioning signal after 15 min of sevoflurane administration. The 15 min duration might be too short or the concentration of sevoflurane too low to induce cardioprotection detected by troponin I levels.

A quality control programme for acute myocardial infarction management in out-of-hospital critical care medicine.

This study, conducted over two time periods, aimed to evaluate the effectiveness of the diffusion of data, implementation of correctives measures and updated protocols in reducing time to reperfusion in acute myocardial infarction (AMI) management in the out-of-hospital setting. Mean (SD) time to hospital admission and to arterial puncture improved (58 (13) vs 67 (18) min, p = 0.03; and 82 (16) vs 95 (29) min, p = 0.02). The study, performed according to quality control programme methodology, showed that the chronology of AMI management could be improved by appropriate interventions and monitoring of intervention times.

Efficacy of intraoperative dexmedetomidine compared with placebo for surgery in adults: a meta-analysis of published studies.

Dexmedetomidine (Dex) demonstrates sedative and analgesic effects. We investigated the intraoperative and postoperative effects of intraoperative Dex administration during surgery in adult patients. A search for randomized placebo-controlled trials was conducted in Pubmed and Embase databases to identify randomized controlled clinical trials using intraoperative Dex for surgery in adult population. Outcome assessed were: intraoperative and postoperative opioid consumption, time of recovery from anesthesia, postoperative pain, and postoperative nausea or vomiting (PONV) in the first 24 hours. Data from each trial were combined to calculate pooled odds ratios (OR), mean difference (MD) or standardized mean difference (SMD) and 95% confidence interval (95 % CI). Heterogeneity was measured using I² statistics. Eighteen randomized controlled trials were analyzed. Dex was administered to 815 patients and 410 received placebo. Overall, Dex significantly decreased intraoperative opioid consumption (SMD=-1.58 [-2.98, -0.19], I²=95 %, P<0.00001), but did not decrease time of recovery from anesthesia (SMD=-0.13 [-1.60, 1.34] minutes, I²=95 %, P<0.00001). Dex significantly reduced postoperative opioid consumption (SMD=-1.58 [-2.98, -0.19], I²=95 %, P<0.00001), postoperative pain intensity (SMD=-0.73 [-1.19, -0.27], I²=62 %, P=0.03), and the prevalence of PONV (OR=0.43 [0.27, 0.69], I²=0 %, P=0.46). This meta-analysis shows that intraoperative Dex administration in adult patients reduces intra and postoperative opioid consumption, postoperative pain and PONV. Time of recovery is not affected.

Differential effects of ascending neurons containing dopamine and noradrenaline in the control of spontaneous activity and of evoked responses in the rat prefrontal cortex.

The medial prefrontal cortex receives converging projections from the mediodorsal thalamic nucleus, dopaminergic cells from the ventral tegmental area dn noradrenergic cells from the locus coeruleus. Stimulation of the ventral tegmental area inhibits the spontaneous activity of prefrontal cortical neurons and blocks the excitatory response evoked by stimulation of the mediodorsal thalamic nucleus (10 Hz). The aim of the present study was to compare the influence of dopaminergic and noradrenergic afferents on the spontaneous and evoked activity of medial prefrontal cortical neurons. In ketamine-anaesthetized rats, repetitive stimulation (20 Hz, 10 s) of the locus coeruleus produced a long-lasting post-stimulus inhibition (mean duration: 45 s) of the spontaneous activity of 56% of the tested cells. This effect was decreased markedly following selective destruction of the ascending noradrenergic pathways (local 6-hydroxy-dopamine injection) or depletion of cortical catecholamines by alpha-methyl-para-tyrosine pretreatment, suggesting that these inhibitory responses are mediated by noradrenergic neurons. The excitatory response to mediodorsal thalamus nucleus stimulation (10 Hz) could still be evoked during the post-stimulus inhibitory period induced by locus coeruleus stimulation (20 Hz, 10 s) resulting in the enhancement of signal-to-noise ratio. On the other hand, a population of prefrontal cortex neurons (26%) was found to be reproducibly activated by noxious tail pinch. This evoked response was still present during the post-stimulus inhibitory period induced by locus coeruleus stimulation but was completely suppressed during stimulation of the ventral tegmental area (10 Hz). In conclusion, these results indicate that the dopaminergic and noradrenergic systems exert a completely distinct control of information transfer in the medial prefrontal cortex.

Inhibitory effects of ventral tegmental area stimulation on the activity of prefrontal cortical neurons: evidence for the involvement of both dopaminergic and GABAergic components.

The medial prefrontal cortex of the rat receives dopamine and non-dopaminergic projections from the ventral tegmental area. Both electrical stimulation of the ventral tegmental area and local application of dopamine induce an inhibition of the spontaneous activity of most prefrontal cortical neurons, including efferent neurons. In the present study, the techniques of extracellular recording and microiontophoresis were used in anesthetized rats in order to determine whether these dopamine- and ventral tegmental area-induced inhibitory responses involve GABAergic components. Prefrontal cortex output neurons were identified by antidromic activation from subcortical structures. The inhibitory responses evoked by the local application of dopamine were blocked by the iontophoretic application of the D2 antagonist sulpiride, and the GABAA antagonist bicuculline in 89 and 57% of the cases, respectively. In addition, sulpiride and bicuculline abolished the inhibition induced by ventral tegmental area stimulation in 54 and 51% of the prefrontal cortical cells tested, respectively. The implication of a non-dopaminergic mesocortical system in the ventral tegmental area-induced inhibition was further analysed using rats pre-treated with alpha-methylparatyrosine to deplete dopamine stores. The proportion of prefrontal cortical cells inhibited by ventral tegmental area stimulation was markedly reduced (39%) in alpha-methylparatyrosine-treated rats, when compared to controls (86%). Remaining ventral tegmental area-induced inhibition was no longer affected by sulpiride, but in all cases blocked by the local microiontophoretic application of bicuculline. The present results suggest that: (1) the dopamine-induced inhibition of prefrontal cortex neurons could involve cortical GABAergic interneurones; (2) the non-dopaminergic mesocortical system exerts also an inhibitory influence on prefrontal cortical cells and appears to be GABAergic.

Beta-adrenergic receptor changes during coronary artery bypass grafting.

To evaluate whether the function of beta-adrenergic receptors, essential to the biologic activity of catecholamines, is altered during coronary artery bypass grafting, we measured, in 16 patients undergoing myocardial revascularization, the density and the affinity of lymphocyte beta-adrenergic receptors before anesthesia induction (control) and at the end of cardiopulmonary bypass. Variations in the density and affinity of beta-adrenergic receptors were determined in vitro. Repeated determinations of plasma epinephrine and norepinephrine concentrations were also performed. Overall, no significant modification was observed in mean density and affinity of beta-adrenergic receptors at the end of cardiopulmonary bypass when compared with control values. However, a significant decrease (p less than 0.05) in affinity for isoproterenol was found in the six patients who had high catecholamine levels during cardiopulmonary bypass. In contrast, no significant modification of beta-adrenoreceptor affinity for isoproterenol was observed in the 10 patients who did not have this degree of adrenergic activation. In addition, beta-adrenoreceptor affinity for isoproterenol was decreased in the three patients in whom intraaortic balloon pumping was mandatory after discontinuation of cardiopulmonary bypass. We suggest that this decreased affinity of lymphocyte beta-adrenergic receptors could be related, at least in part, to a sustained adrenergic activation occurring in some patients during cardiopulmonary bypass.