Dysconjugate gaze in hepatic coma

During an episode of hepatic encephalopathy, an elderly woman developed ocular divergence at rest and dysconjugate gaze after caloric stimulation. Metabolic encephalopathy may rarely produce oculomotor dysfunction, usually attributed to structural brainstem lesions.     

Human tryptamine metabolism decreases during night sleep

Fourteen healthy male volunteers took part in a study which aimed to determine whether utilization of tryptamine changes in relation to sleep and wakefulness. For this purpose urine samples were collected every 4 hr and urinary tryptamine and indoleacetic acid (IAA) were determined by fluorometric and spectrophotometric methods. Urinary concentration of IAA progressively increased during the day and fell during the night when subjects were asleep but not when subjects were awake. This evidence indicates that behavioral state rather than circadian variation determines the level of urinary IAA. Tryptamine (T) concentration also progressively increased during the day and continued to increase during the night. The mean log10 (IAA/T) ratio indicates that tryptamine metabolism decreases during the night when subjects are asleep. Therefore, human sleep may be associated with diminished activity of peripheral tryptamine.     

Octanoic acid-induced coma and reticular formation energy metabolism

The medium chain fatty acid octanoic acid was injected i.p. into 20-22 g Swiss-Albino mice at a dose of 15 mumol/g. This dose produced a reproducible response consisting of a 3-4 min period of drowsiness, followed by coma. These mice as well as suitable controls were sacrificed by rapid submersion in liquid N2, or by microwave irradiation in a 7.3 kW microwave oven. Tissue from the reticular formation and the inferior colliculus was prepared for microanalysis of the energy metabolites glucose, glycogen, ATP and phosphocreatine. Results from this study showed a selective effect on energy metabolism in cells of the reticular formation. Both glucose and glycogen were elevated in the coma and precoma state. In addition, ATP and phosphocreatine were decreased in the reticular formation during coma. These results show a selective effect of octanoic acid on energy metabolism in the reticular formation both in the precoma stage, and during overt coma. The selective vulnerability of the reticular formation to metabolic insult may act in a beneficial manner to the animal by inducing coma. This lowers the overall demand for energy, thereby placing the animal in a milieu in which there is an increased chance for correction of the perturbation.     

Insulin-induced hypoglycemic coma and regional cerebral energy metabolism

Swiss-Albino female mice weighing 20 g were rendered hypoglycemic by injecting insulin (2 units/kg). Animals were sacrificed at 40 min (pre-coma), 2 h (coma) and 4.5 h (recovery) after insulin injection by rapid submersion in liquid N₂. Following sectioning at 20 μm, samples from the ascending reticular activating system and the inferior colliculus were freeze-dried and assayed for glucose, lactate, ATP and phosphocreatine (PCr).There was a preferential effect of hypoglycemia on ATP and PCr in cells of the ascending reticular activating system. ATP was depleted 30%, and PCr 55% in the pre-coma stage. ATP and PCr in cells from the inferior colliculus were not decreased. This selective effect on cells of the ascending reticular activating system followed by coma suggests that the coma per se may not represent total failure of the organism, but rather a compensatory mechanism designed to permit the animal to correct its compromised energy status.     

CNS energy metabolism as related to function

Large amounts of energy are required to maintain the signaling activities of CNS cells. Because of the fine-grained heterogeneity of brain and the rapid changes in energy demand, it has been difficult to monitor rates of energy generation and consumption at the cellular level and even more difficult at the subcellular level. Mechanisms to facilitate energy transfer within cells include the juxtaposition of sites of generation with sites of consumption and the transfer of P by the creatine kinase/creatine phosphate and the adenylate kinase systems. There is evidence that glycolysis is separated from oxidative metabolism at some sites with lactate becoming an important substrate. Carbonic anhydrase may play a role in buffering activity-induced increases in lactic acid. Relatively little energy is used for ‘vegetative’ processes. The great majority is used for signaling processes, particularly Na⁺ transport. The brain has very small energy reserves, and the margin of safety between the energy that can be generated and the energy required for maximum activity is also small. It seems probable that the supply of energy may impose a limit on the activity of a neuron under normal conditions. A number of mechanisms have evolved to reduce activity when energy levels are diminished.     

Drugs that escape hepatic metabolism

There are several situations in which the hepatic metabolism of drugs may differ from that expected, resulting in possibly compromised efficacy or increased adverse effects. These situations are: When patients are slow or rapid metabolizers; when patients receive co-therapy with metabolic enzyme inducers or inhibitors; and when patients have impaired liver function. This article considers anxiolytic, antidepressant, antipsychotic, mood stabilizer, anticonvulsant, and anti-dementia drugs that are useful in such situations. A few metabolic drug interactions are briefly discussed.     

Neurophysiological recovery after hypoglycemic coma in the rat: correlation with cerebral metabolism

Recovery of electroencephalographic activity and somatosensory evoked responses was studied in paralyzed and lightly anesthetized (70% N2O) rats in which profound hypoglycemia had been induced by insulin administration. The duration of severe hypoglycemia was defined as the duration of a flat electroencephalogram (EEG) recording (5, 30, and 60 min, respectively) before restitution with glucose. The restitution period was followed by continuous EEG monitoring and repeated tests for evoked potentials. After 180 min of recovery, the brains were frozen in situ with liquid nitrogen and analyzed for energy metabolism. In accordance with earlier metabolic studies from this laboratory, the recovery after 60 min of severe hypoglycemia was incomplete, with signs of permanent failure of energy metabolism. There was persistent ATP reduction proportional to the duration of the hypoglycemia. The short-term recovery of EEG and sensory evoked responses was proportional to the duration of severe hypoglycemia. The neurophysiological recovery after 5 min of severe hypoglycemia was complete. After 30 min of severe hypoglycemia, the evoked responses recovered but showed a significant prolongation of latency, compared with normal. After 60 min of severe hypoglycemia, no early evoked response and scanty EEG activity were observed. The neurophysiological observations indicate a persistent deficit of synaptic transmission in the somatosensory pathway, including the cortical projection. This can be correlated with neuropathologic changes that are particularly prominent in intermediate cortical layers, as previously shown.     

Resistance of brain glucose metabolism to thiopental-induced CNS depression in newborn piglets

The transition from mild sedation to deep anaesthesia is marked by the phenomenon of burst suppression (BS). FDG-PET studies show that the cerebral metabolic rate for glucose (CMRglc) declines dramatically with onset of BS in the adult brain. Global CMRglc increases substantially in the post-natal period and achieves its maximum in preadolescence. However, the impact of post-natal brain development on the vulnerability of CMRglc to the onset of BS has not been documented.