Delayed recovery of behavior after anesthesia in rats.

UNLABELLED: Early, complete recovery from general anesthesia is of importance for outpatients, in resuscitation research and in behavior testing of neonates. A model was designed to study behavior during the first week of recovery from anesthesia in rats, using two methods: spontaneous and unrestrained locomotor activity was tested and passive avoidance of electroshock was studied in a two session, one trial model. Neurologic deficit and ease of handling were also tested. After anesthesia with halothane 1-2% in N2O/O2 for 30 min, spontaneous activity was reduced, compared with unanesthetized rats, for up to at least 48 h. On day 6 post-anesthesia, locomotor activity was recovered, and, on days 4 and 5, passive avoidance was unchanged. Neurologic deficits were absent after the first hour of recovery and ease of handling was unchanged. CONCLUSION: Halothane and nitrous oxide have prolonged effects on locomotor behavior beyond the immediate post-anesthesia recovery period, at a time when neurologic deficit testing does not reveal any abnormalities. The model is suitable for the comparison of recovery from different anesthesia techniques in rats.

Brain lactate and alanine-glutamate ratios during and after asphyxia in rats.

Recently, Conger, Garcia, Kauffman, Lust, Murakami and Passonneau, (1981) proposed the use of brain alanine-glutamate ratios (A:G) for the prediction of outcome after brain ischemia. This study evaluates this parameter and brain lactate concentration during and after asphyxial insults in rats. During the first 15 min of asphyxial death in rats (n = 37), lactate increased sharply from mean values of 1.48 to 18.06 mumol g-1 wet brain, and thereafter to 19.44 mumol g-1 wet brain at 180 min. During total body asphyxia (n = 38) and recovery after resuscitation, brain lactates increased to mean values of 15 and 17.5 mumol g-1 wet brain at 5 and 10 min, respectively, to recover after 30-60 min to baseline. The alanine-glutamate ratios did not rise during the insult; however, after restoration of circulation, the ratios rose to peak at about 15 min post-restoration of circulation and recovered slowly during the next 165 min to still slightly increased levels. During intermittent asphyxia (n = 15), lactate and alanine-glutamate ratios followed the same patterns as found before except at lower levels. The conclusions of this study are: (1) brain lactate concentrations had no value in predicting the potential of recovery; (2) increased lactate concentrations during recovery indicated secondary insult; (3) brain A:G's did not increase during asphyxiation; (4) brain alanine-glutamate ratios increased after restoration of circulation and may have reflected the quality of reflow; (5) increased ratios during recovery beyond 20 min indicated secondary insult. Brain alanine-glutamate ratios could not be used for prediction of outcome in asphyxial insults in rats.

Asphyxia, cardiac arrest and resuscitation in rats. II. Long term behavioral changes.

This study in 53 rats was conducted to investigate a mild insult, sensitive parameter model in contrast to a severe insult, severe damage model of brain resuscitation. Up to now, the latter approach, which causes neuropathologic changes and neurological abnormalities, has not provided unequivocal data on pharmacological measures to ameliorate post-anoxic brain damage, because of logistical difficulties and many extracranial complicating factors. As tracheotomy and oral intubation in rats proved impractical in studies on recovery from asphyxia, transtracheal jet ventilation was tested in 14 rats as a measure for effective prolonged and reversible control of airway and ventilation. Subsequently, in 37 other rats we studied, during the first post-insult week, the effects of anesthesia, with or without 6 min asphyxia, on behavior, i.e. unrestrained spontaneous locomotor activity and two sessions of one-trial passive avoidance. Transtracheal jet ventilation proved a reliable method for reversible and prolonged controlled ventilation in rats. Spontaneous locomotor activity was affected for at least 48 h after anesthesia and differently so after asphyxia. Passive avoidance was affected only after asphyxia. The recovery of behavior was delayed for days, whereas the recovery of neurologic deficits was only delayed for several post-asphyxia hours. The asphyxiated rats showed hyper-excitability for at least 2 weeks. The existence of abnormal behavior during recovery from mild anoxic-ischemic insults to the brain provides parameters for evaluation of therapies of the post-resuscitation disease in a model without the difficulties encountered in models with severe insults, which made post-insult intensive care necessary. The mild insult, sensitive parameter model is promising and further work in this direction is indicated.

Asphyxia, cardiac arrest and resuscitation in rats. I. Short term recovery.

This study was conducted to investigate the degree of insult from asphyxia leading to total body circulatory arrest, as a model for brain resuscitation studies in rats. Of 78 male rats, 68 were anesthetized with halothane in O2/N2O, controlled ventilated, paralyzed with pancuronium and asphyxiated, 5, 7.5, 10, 12.5 and 15 min, respectively. Asphyxiation led to circulatory arrest in 244 +/- 22 s (mean +/- S.E.M.). Resuscitation was successful in 65% within 60 s using controlled ventilation with 100% O2, extrathoracic compressions and epinephrine intravenously. Subsequent intensive care to 6, 12 or 24 h was successful in 50% of resuscitated rats. At 6, 12 and 24 h of recovery, neurologic deficit scores and light microscopic neuropathology scores of the brain after in vivo fixation of the total body with intraventricular paraformaldehyde 3%, revealed a large scatter variability without a clear pattern. Lesions were located mostly in the frontal cortex and hippocampus (footplate) with ischemic neuronal change as the most frequent structural change. Brain cell necrosis was not seen after successful resuscitation. It seems that both scores were influenced by post-insult stress, as indicated by paroxysmal hypertension and motor activity, by complications, such as obstruction of the tracheotomy cannula by abundant sputum production, and by partial sedation with N2O and paralysis with pancuronium. This study indicates the feasibility of an asphyxial insult in rats for use in resuscitation studies of short duration. Although 24 h post-insult recovery is possible, up to 6 h seems most practical, with asphyxia of 7.5-10 min most successful and controllable. Questions are raised about the effects of irritation during the post-insult intensive care on both neurological deficit and neuropathology scores.

[Short-term transtracheal jet for reversible support of respiration in the rat]. / Zeitlicher transtrachealer Jet für die reversible Unterstützung der Atmung bei Ratten.

A method is described for reversible controlled ventilation of rats by transtracheal catheter (20 or 22 G). A small rodent ventilator is used, rather then a jet ventilator, because the former enables the mixing of inhalation anesthetics with the carrying gas mixture. The method proved to be the most successful one for weaning from controlled ventilation after cardiac arrest and resuscitation of rats. In general, the method can be considered as an alterative to oral intubation and tracheotomy for controlled ventilation in rats.

Thiopental treatment after global brain ischemia in pigtailed monkeys.

The authors investigated the value of high-dose thiopental (TH) therapy after 16-min complete global brain ischemia (GBI) in three groups of pigtailed monkeys, using a neck cuff model of GBI with 96 h intensive care postischemia (PI). Control group (n18): Normotension was restored within 2 min PI; paralysis/controlled ventilation was maintained for 48 h PI with 50% N2O/O2. Thiopental loading group (n13): Control treatment plus TH-loading with 90 mg/kg iv given from 5 to 65 min PI (mean peak TH plasma level 130 micrograms/ml). Thiopental anesthesia group (n14): Control treatment plus TH anesthesia with 90 mg/kg iv given over 12 h PI (sustained TH plasma levels of 25-35 micrograms/ml and EEG burst suppression). Norepinephrine requirement for blood pressure control PI was greater in the TH groups than in the control group (P less than 0.05). Lidocaine was needed for control of arrhythmias in the TH loading group. There was no significant difference in mortality or neurologic outcome between the groups. At 96 h PI seven of 11 animals were awake in the control group, compared with seven of 12 and six of 12 in the two TH groups. Neurologic deficit scores (NDS) for the survivors at 96 h PI were 23 +/- 6% (mean +/- SD) (n10) in the control group, compared with 25 +/- 9% (n11) and 26 +/- 12% (n10) in the two TH groups (NDS 100% = brain death, 0% = normal). Seizures PI (in 1-2 of each group) were associated with worse neurologic deficits.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of suxamethonium on the potency of ORG NC 45 in anaesthetized patients.

The non-depolarizing neuromuscular block produced by Org NC 45 was potentiated by the previous administration of suxamethonium 1 mg kg-1, shown by twitch depression of 91.3 +/- 2.4% when the same dose of Org NC 45 was administered after recovery from suxamethonium compared with the control value of 71.9 +/- 6.5%. The recovery index was also prolonged from 8.1 +/- 0.3 to 10.4 +/- 1.0 min after suxamethonium. The dose-response curves for Org NC 45 showed a 1.66 potentiation factor for ED50 and 1.73 for ED95, caused by the previous administration of suxamethonium. This interaction is likely to occur in the plasma.

Comparative study of the different factors influencing resistance of tubes to gas flow.

With the help of a pneumotachograph and a pressure transducer the influences of tube diameter, tube length, tube shape, connectors of different shape and kinking are quantified. The influence of different gases on resistance is calculated. With the help of the shown data one can predict the influence of changes of the different factors. Rules for optimalisation are given and their clinical significance is discussed. Most significant factors are diameter and length of the tube, kinking over 50% and kinematic viscosity and density of the used gas mixture.