Circulatory and metabolic effects in the brain induced by amphetamine sulphate

Cerebral circulatory and metabolic effects of amphetamine sulphate (0.25-25 mg.kg-1 i.v. or 5-10 mg.kg-1 i.p.) were studied in anesthetized, paralyzed and artifically ventilated rats. Cerebral blood flow (CBF) was measured with a modification of the Kety and Schmidt (1948) technique, and oxygen consumption (CMRO2) was calculated from CBF and arteriovenous differences in oxygen content. Regional CBF was evaluated from the uptake of 14C-ethanol. Cortical metabolites were analysed following freezing of tissue in situ. Amphetamine administration gave rise to a marked increase in CBF that was doubled following 0.25 mg.kg-1 and increased 4-fold following 15 mg.kg-1. However, such excessive increases in flow were confined to frontoparietal cortical regions, while other cortical or subcortical areas showed more moderate hyperemia. The increase in CBF was unrelated to changes in arterial PCO2, blood pressure, or tissue lactate content. CMRO2 increased by 30% to 95% depending on dose and rat strain used. At all doses employed, amphetamine gave rise to glycogenolysis in cerebral cortex but, in animals studied within the first 30 min after 5 mg.kg-1, or less, the only other changes were increases in glucose-6-phosphate and alpha-ketoglutarate concentrations. When the dose was increased to 15 mg.kg-1, there were moderate increased in lactate concentration and lactate/pyruvate ratio. Sixty min after 5 mg.kg-1 there were increases in tissue concentrations of pyruvate, citric acid cycle intermediates and alanine, as well.     

Premedication with intramuscular dixyrazine: (Esucos®)

Ninety patients scheduled for general or orthopaedic surgical procedures were randomly assigned to receive one of three i.m. premedications: dixyrazine 0.5 mg kg-1; morphine 0.15 mg kg-1 and scopolamine 0.0065 mg kg-1; or placebo. The premedication was administered and evaluated in a double-blind fashion. The patients were anaesthetized with thiopentone, fentanyl, pancuronium, and ventilated with nitrous oxide in oxygen. The three premedications had no noticeable anxiolytic effect. Although there was no difference in the frequency of observed postoperative nausea and vomiting between the three groups, premedication with dixyrazine nonetheless reduced the patients' experience of postoperative nausea as well as their need for postoperative antiemetics. Although patients in the two treatment groups were significantly more sedated immediately before induction of anaesthesia than patients receiving placebo, the degree of postoperative sedation was similar in all three groups. Morphine-scopolamine caused more postoperative dizziness than dixyrazine and placebo. Lack of recall was produced by both morphine-scopolamine and dixyrazine. It is concluded that premedication with dixyrazine is a useful alternative, especially in patients who have previously experienced postoperative nausea and vomiting.     

Electroencephalographic Study of Children During Ketamine Anesthesia

EEG was recorded on nine occasions of ketamine anesthesia in eight children. Two of the patients were neurologically normal and six were under investigation for various neurological disorders. The EEG during the catatonic phase of ketamine anesthesia is characterized by alternating high amplitude delta complexes and periods of fast activity. The two cases which in the routine EEG showed focal paroxysmal activity did not show any electroencephalographic aggravation or clinical seizure during ketamine influence. One case exhibiting a subcortical type of epileptiform activity showed a marked potentiation of this activity with ketamine. On routine neurological examination during the catatonic phase of ketamine anesthesia the pharyngeal reflex was generally weak and failed altogether in two cases and corneal reflexes were absent in three cases.     

Myocardial protection during heart surgery. An experimental evaluation of normothermic and hypothermic cardioplegia.

Heart surgery with hypothermic cardioplegia during normothermic bypass is sometimes complicated by rewarming of the myocardium caused by collateral flow of arterial blood. This problem is particularly evident in surgery of congenital malformations. The present work is a comparative study in dogs on 3 methods of avoiding the rewarming problem. In the first group, the heart was kept cold and the warm blood was drained off from the left atrium. In the second group, total body hypothermia to the level desired was used and in the third group, normothermic cardioplegia was induced (Cardioplegin) in normothermic animals. In the two latter groups, the undesired temperature gradient between heart and body was eliminated. Evaluation of the differences was made by means of ventricular function determinations. Local, hypothermic cardioplegia showed the best postoperative function (69%) followed by the total body cooling which was fully acceptable (41%). Normothermic cardioplegia after the same duration of arrest showed a too low myocardial performance (20%).     

Cerebral Metabolic State after Discontinuation of Nitrous Oxide Supply in Artificially Ventilated Rats

Previous results from this laboratory have shown that when administration of 70% nitrous oxide is discontinued in artificially ventilated rats, cerebral oxygen uptake increases by about 40 % at 5 min and by about 80–905; at 30 min, and that this increase is blocked by previous adrenalectomy. In the present experiments, nitrous oxide was withdrawn for 45 s, 2 min 45 s, or 15 min, in non-adrenalectomized animals. and for 5 min in adrenalectomized animals, and the tissue was frozen in situ for subsequent measurements of labile phosphates, glycolytic metabolites, citric acid cycle intermediates and associated amino acids, and ammonia. The results allow the conclusion that upon withdrawal of nitrous oxide in non-adrenalectomized animals, there is an increase in metabolic rate at an essentially unchanged metabolic state. In adrenalectornized animals, discontinuation of nitrous oxide supply did not induce changes in any of the tissue metabolites measured. We conclude that 70% N₂O neither influences the metabolic rate of the tissue, nor its metabolic state.     

Anaesthesia for cardioversion — clinical experiences with propofol and thiopentone

A 1-year population of anaesthesias for cardioversion of supraventricular tachyarrhythmias was studied. Propofol and thiopentone were used alternately for every other procedure, and the anaesthetic-, and monitoring procedures were prospectively standardized. Twenty-one thiopentone- and 23 propofol-anaesthetized patients, who had been subjected to elective cardioversions of atrial fibrillation were compared, particularly regarding possible differences in the energy requirements for cardioversion and in the time intervals to initial awakening. There were no significant differences between the two drugs in the maximum systolic blood pressure drop, in the total mean energy requirements per kg bodyweight, or in the distribution of the number of patients over the various energy levels needed for restoration of sinus rhythm. Somewhat unexpectedly, however, the mean time interval to initial awakening was significantly longer in the propofol-anaesthetized group. Apart from this minor drawback, propofol proved to be as useful an anaesthetic agent as thiopentone for the cardioversion procedure, and may be considered as an alternative drug in selected cases.     

Protective effect of hypothermia in cerebral oxygen deficiency caused by arterial hypoxia.

To study the cerebral protective effects of hypothermia in arterial hypoxia, anesthetized (70% N2O), mechanically ventilated rats were cooled to a body temperature of 27 C. Hypoxia was induced by decreasing the oxygen content in the inspired gas mixture either to 6-7 per cent or to 2.5-3 per cent. This reduced mean PaO2 to about 25 and 11-12 torr, respectively. At PaO2 torr, there was no change in cerebral blood flow (CBF), cerebrla oxygen consumption (CMRO2), or labile tissue metabolites. The absence of signs of cerebral hypoxia could be attributed to an effect of temperature and pH on the hemoglobin-oxygen dissociation curve. Thus, at 27 C with a PaO2 of 25 torr the total oxygen content (TO2) of arterial blood remained greater than 15 ml (100 ml)-1, about three times the value obtained at this PO2 in normothermic rats. At PaO2 11-12 torr, arterial TO2 was reduced to about 5 ml (100 ml) (-1). The hypoxia induced no change in CMRO2, a threefold increase in CBF, a moderate lactacidosis in the tissue, and a small decrease in phosphocreatine content, but no change in ATP, ADP, or AMP. These changes are less marked than those occurring at the same arterial TO2 in normothermic rats. It is concluded that hypothermia exerts a pronounced protective effect on the brain in hypoxic hypoxia, and that two mechanisms are involved. First, since hypothermia shifts the oxyhemoglobin-dissociation curve towards the left, and prevents or minimizes a rightward shift due to acidosis, it maintains a high TO2 in arterial blood at a given PaO2. Second, by reducing CMRO2, and thereby presumably also cellular energy requirements, hypothermia exerts a protective effect at the cellular level.     

Influence of Changes in Arterial PCO2 on Cerebral Blood Flow and Cerebral Energy State during Hypothermia in the Rat

In order to study the relationship between arterial P_CO2 and cerebral blood flow (CBF) in hypothermia, the body temperature of artificially ventilated rats was decreased to 22C, and changes in CBF were evaluated from arteriovenous differences in oxygen content (AVD_O2) at Pa_CO2 values of 15, 30, 40 and 60 mm Hg. The results were compared to those obtained at normal body temperature (37C) over the Pa_CO2 range 15–60 mm Hg. Separate experiments were performed to evaluate CBF and CMR_O2 at 22C and a Pa_CO2 of 15 mm Hg, using an inert gas technique for CBF. The tissue contents of phosphocreatine, ATP, ADP, AMP and lactate were measured in hypothermic animals at Pa_co2values of 15, 30 and 60 mm Hg.
The results showed that changes in CBF were of the same relative magnitude in hypothermia and normothermia when Pa co2 was increased from about 35 to about 60 mm Hg. However, with a decrease in Pa_CO2 the reduction in CBF was much more pronounced in hypothermia, and at Pa_CO2 15 mm Hg CBF was less than 20 % of the value measured in normothermic and normocapnic animals. The results of the metabolite measurements gave no evidence of tissue hypoxia in spite of the pronounced reduction in CBF. Although the results demonstrate that the brain of a hypothermic animal is protected against the harmful effects of a lowered CBF, it may not warrant recommending hyperventilation in clinical cases of hypothermia, especially not in patients with arteriosclerosis or cerebrovascular diseases.