A magnetic resonance spectroscopic imaging study of adult nonhuman primates exposed to early-life stressors.

BACKGROUND: Long-term behavioral, immunologic, and neurochemical alterations have been found in primates exposed to adverse early rearing. METHODS: Bonnet macaque (Macaca radiata) mother-infant dyads were exposed to uncertain requirements for food procurement (variable foraging demand, VFD) for a few months. Ten years later, these offspring and age- and gender-matched control subjects were studied using proton magnetic resonance spectroscopic imaging (MRSI). RESULTS: In anterior cingulate, VFD-reared subjects displayed significantly decreased N-acetylaspartate (NAA) resonance and significantly increased glutamate-glutamine-gamma-aminobutyric acid (Glx) resonance relative to the stable neurometabolite creatine (Cr). Across all subjects, NAA/Cr and Glx/Cr ratios in the anterior cingulate were negatively correlated (r = -.638, p =.014). In the medial temporal lobe, the ratio of choline-containing compounds to Cr was significantly increased in VFD subjects. CONCLUSIONS: These findings indicate that adverse early rearing in primates has an enduring impact on adult MRSI measures considered reflective of neuronal integrity and metabolism, membrane structure and glial function, and cerebral glutamate content, and that these alterations occur in the same brain regions implicated in trauma-related psychiatric disorders.

Anaesthesia of the common marmoset (Callithrix jacchus) using continuous intravenous infusion of alphaxalone/alphadalone.

A safe means of anaesthetizing common marmosets (Callithrix jacchus) for a study using magnetic resonance imaging (MRI) to investigate cerebral ischaemia was required. Continuous infusion of alphaxalone/alphadalone was used to anaesthetize 37 marmosets for non-recovery and recovery experiments. This was found to give safe, reliable anaesthesia when coupled with pulse oximetry and electrocardiographic (ECG) monitoring.

Effects of inhalation and intravenous anesthetic agents on pressor response to NG-nitro-L-arginine.

The effects of anaesthetic agents on pressor effect of NG-nitro-L-arginine (L-NNA), a potent inhibitor of nitric oxide (NO) synthesis, were examined in rats. I.v. bolus of L-NNA (1-32 mg/kg) in conscious rats dose dependently increased mean arterial pressure (MAP) to a maximum value of 53 +/- 2 mmHg at 16 mg/kg with ED50 value of 4.7 +/- 0.9 mg/kg. The effects of a single i.v. bolus dose (32 mg/kg) of L-NNA were examined in conscious rats and rats anaesthetised with pentobarbital, chloralose, ketamine, althesin (mixture of alphaxalone and alphadolone), urethane, enflurane or halothane. In conscious rats, peak MAP (51 +/- 3 mmHg) was reached 10 min after i.v. injection and the effect lasted more than two hours. The magnitudes of peak MAP differed under the influence of anaesthetic agents with the following rank order: althesin greater than conscious = pentobarbital = chloralose = ketamine = urethane greater than enflurane much greater than halothane (in which there was negligible change in MAP). The onsets were delayed in rats anaesthetised with pentobarbital, althesin, chloralose and enflurane but not altered with ketamine and urethane compared to that in conscious rats. Therefore, L-NNA caused intense and prolonged pressor response in conscious rats and rats anaesthetised with the i.v. anaesthetic agents pentobarbital, chloralose, ketamine, althesin and urethane. MAP effect of L-NNA was markedly attenuated by the inhalation anaesthetics halothane and enflurane.

Continuous EEG and ICP monitoring as a guide to the administration of althesin sedation in severe head injury.

The effects of 142 intravenous boluses of althesin (0.05 ml/kg) on cerebral perfusion pressure (CPP) were studied in twelve head injured comatose patients. The data were divided into those where the mean pre-bolus intracranial pressure (ICP) was above or below 20 mmHg and then subdivided into those where the minimum pre-bolus voltage of the cerebral function monitor (CFM) was above or below 5 microV (representing marked reduction in cortical electrical activity). The pre-bolus ICP influenced the extent of the fall in ICP and thus the direction of the resulting change in CPP. A mean reduction in CPP was observed in both groups in which ICP was below 20 mmHg irrespective of the CFM voltage. In the subgroups with high ICP, CPP increased when CFM was not depressed and fell when CFM was below 5 microV. The effects of individual boluses varied within and between the subgroups and, occasionally, severe and unpredictable hypotension occurred. If althesin administration had been restricted to the high CFM and high ICP group, 90% of the episodes of reduced CPP would have been avoided. In fact, when cortical electrical activity is already severely depressed, further administration of hypnotic anaesthetic agents produces only small reductions in ICP and usually a fall in CPP. These findings suggest that the minimum voltage of the CFM trace is a clinically useful guide to the administration of intravenous anaesthetic agents and offers a relevant prediction of their effects on CPP.

Some predisposing factors to hypersensitivity reactions following first exposure to Althesin.

Three possible factors predisposing to Althesin hypersensitivity, namely total dose, method of administration, either by bolus dose or infusion, and pregnancy have been studied in patients receiving the drug for the first time. Of 137 patients given Althesin, four exhibited clinical signs of mild hypersensitivity, while C3 conversion alone, indicative of a subclinical reaction, was seen in a further six patients. No reactions were observed in two control groups in whom anaesthesia was induced with thiopentone. Neither the total dose nor method of administration appeared consistently to influence the incidence of reactions, but eight of the ten patients producing an altered response to Althesin were pregnant.

Use of a continuous infusion of althesin in neuroanaesthesia. Changes in cerebral blood flow, cerebral metabolism, the EEG and plasma alphaxalone concentration.

Ten patients with small supratentorial tumours were studied during craniotomy. Cerebral blood flow (CBF) was measured in the contralateral hemisphere by a modification of the Kety and Schmidt technique using xenon-133 i.v. With an Althesin infusion rate of 0.2 ml kg-1 h-1, CBF was 24.4 +/- 5.4 ml min-1/100 g and CMRO2 1.87 +/- 0.44 ml min-1/100 g at PaCO2 4.1 +/- 0.7 kPa (mean +/- SD). During constant infusion rates of Althesin, steady values of CMRO2 were obtained, while an increase in infusion rate of 150% was associated with an increase in plasma alphaxalone concentration, a decrease in CMRO2 and a tendency of further EEG suppression. However, great inter- and intraindividual variations were present, and correlations between CMRO2, EEG activity and plasma alphaxalone concentration were weak.

[Anesthetic induction with Althesin or diazepam in patients undergoing an aortocoronary bypass]. / Induction anesthésique avec Alfatésine ou diazépam chez des patients opérés pour pontage aorto-coronarien.

The haemodynamic effects of induction of anaesthesia with diazepam (group D) and Althesin (group A) were studied in 25 coronary patients under betablockers with good myocardial function. Haemodynamic variables monitored were vascular pressures, cardiac output and systolic time intervals. The effects of both drugs were observed when used alone (time I) and in combination with fentanyl, pancuronium and nitrous oxide (time II). The results seemed to show that Althesin (12.51% fall in SI and 10.79% increase in PEP/LVET) depressed myocardial function more than diazepam (no significant difference), but the introduction of fentanyl, pancuronium and nitrous oxide removed the differences between the drugs as to their effect on myocardial performance. These drugs added a depressant effect to diazepam (13.83% fall in SI and 15.77% increase in PEP/LVET) without increasing Althesin's negative inotropic effect. However, in group A at time II, the pulmonary arterial pressure, the wedge pressure and the pulmonary vascular resistance were significantly reduced, while they remained stable in the diazepam group.

[Blood histamine level and anaphylactic reaction under alphadione]. / Histaminémie et réactions anaphylactoïdes sous alfadione.

Histamine release is generally thought to play a major role in anaesthetic-induced anaphylactoid reactions. In 12 patients who were developing such a reaction at the start of a slow rate intra-venous infusion of alphadione, serum histamine was measured using the enzyme-isotopic assay from a blood sample drawn within the first 5 minutes following the onset of clinical signs. Histaminemia above normal value was noted in 3 patients only without clear clinical correlation. These results would suggest that histamine release is unlikely to be principally involved in this kind of adverse reaction.

Age influences the minimum infusion rate (ED50) for continuous infusions of Althesin and methohexitone.

The influence of age has been studied on equipotent rates of continuous infusions of two intravenous hypnotic agents. Two end points have been defined; ED50: the rate needed to suppress the initial response to the surgical incision in 50% of patients, and ED95: the corresponding rate in 95% of patients receiving continuous infusion anaesthesia to supplement 67% nitrous oxide in oxygen. All 210 patients included in the study were premedicated with morphine 0.15 mg kg-1. For patients aged 20-40 years (young group), the ED50 values for Althesin (as alphaxalone) and methohexitone were 14.6 micrograms kg-1 min-1 and 59.9 micrograms kg-1 min-1. The ED95 values were 21.0 micrograms kg-1 min-1 and 92.1 micrograms kg-1 min-1. For patients aged 55-80 years (old group), the ED50 values for Althesin and methohexitone were 11.0 micrograms kg-1 min-1 and 44.2 micrograms kg-1 m in-1, while the corresponding ED95 values were 16.4 micrograms kg-1 min-1 and 76.2 micrograms kg-1 min-1.

Efeitos hemodinâmicos do etomidato, tiopental sódico e alfatesin durante induçäo anestésica e pós-intubaçäo traqueal / Hemodymanic effects of etomidate, sodium thiopental and althesin during anesthesia induction tracheal and post intubation

Os autores comparam-se os efeitos hemodinâmicos do etomidate (0,3 mg. kg-1) durante a induçäo anestésica e após a intubaçäo traqueal com os do tiopental sódico (6-8 mg. kg-1) e Alfatesin (0,4 mg.kg-1) em 90 pacientes distribuídos em 3 grupos de 30. Foram avaliados a frequüência cardíaca, a pressäo arterial sistólica, diastólica e média e o produto da freqüência cardíaca pela pressäo arterial sistólica antes da administraçäo de cada droga, durante a mesma, um minuto após o seu término e imediatamente após a intubaçäo traqueal. O grupo do etomidate mostrou maior estabilidade da freqüência cardíaca e da pressäo arterial, assemelhando-se mais ao grupo do Alfatesin nos momentos anteriores à intubaçäo traqueal. Após a mesma, nos três grupos houve elevaçäo nos valores de todos os parâmetros. Quanto aos efeitos sobre o produto freqüência cardíaca e pressäo arterial sistólica, näo houve diferença significativa entre as três drogas

Infusäo contínua de alfatesin associado ao fentanil / Continous infusion of althesin associated with fentanyl

Vinte e cinco pacientes foram anestesiados usando-se infusäo contínua de Alfatesin associado ao Fentanil. Observou-se o consumo das drogas, os efeitos sobre a pressäo arterial e freqüência cardíaca e as características da recuperaçäo pós-anestésica. O consumo médio de Alfatesin foi de 51,5 + ou - 15 ml correspondendo a uma velocidade de infusäo de 0,0045 ml. kg-1. min-1. O consumo médio de Fentamil foi de 24 + ou - 5,6 ml. Os efeitos cardiovasculares näo foram clinicamente importantes indicando que as drogas produziram alteraçöes hemodinâmicas significativas. Observou-se náuseas e vômitos em 6 pacientes, tremores e calafrios em 11; depressäo respiratória, em 6. Nestes, foi necessário o uso de antagonistas dos narcóticos

Anaesthesia for transcervical thymectomy in myasthenia gravis.

A modified technique of total intravenous anaesthesia was used in the management of 22 patients with myasthenia gravis of varying severity undergoing therapeutic transcervical thymectomy. The relatively short-acting intravenous hypnotics, Althesin and etomidate were compared for induction of anaesthesia and for maintenance as a supplement to 50% nitrous oxide in oxygen. Moderately high doses (20 or 25 micrograms/kg) of the potent, synthetic opiate, fentanyl provided analgesia and a level of respiratory depression sufficient to facilitate control of respiration. The induction of anaesthesia was rapid and smooth, completed in under 5 minutes. Reflex response to surgical stimulation was suppressed for extremely variable periods. Complete recovery of consiousness, or adequate spontaneous respiration and of muscle tone was readily achieved, but was more rapid after Althesin (p less than 0.05). Postoperative problems were few. It is suggested that this technique of anaesthesia can provide optimum operating conditions with rapid, complete recovery and consequently low morbidity; the primary requirements of anaesthesia for therapeutic thymectomy.