The capacity of hypothermia to protect the brain during a period of decreased or absent oxygen delivery(hypoxia) is well established both experimentally and clinically. And also experimentally, barbiturates, which are the most potent pharmacologic depressants of cerebral metabolism, do provide protection. A 25 year-old patien, who had suffered from hypoxic cerebral hypoxia was satisfactorily treated by a combination therapy with Thiopental Sodium and low-grade Hypothermia.
Adult ; Barbiturates ; Brain ; Humans ; Hypothermia* ; Hypoxia, Brain* ; Metabolism ; Oxygen ; Thiopental*

Using a rat model, this study examined the cerebral protective effect of moderate hypothermia and evaluated the effect on early local metabolic change of permanent focal cerebral ischemia. The middle cerebral artery(MCA) of the rat was approached subtemporally and was occluded, and its surface was cooled. Cerebral infarct size was measured at 1, 4 and 7 days after MCA occlusion in non-treated(n=27), 2-hour hypothermia(n=27) and 3-hour hypothermia(n=27) group, respectively, and regional cerebral glucose uptake(rCGU) was determined at 1 and 4 hour after MCA occlusion in the non-treated(n=8) and 3-hour hypothermia(n=8) group, respectively. Infarct size measured at 1, 4 and 7 days after MCA occlusion was 22.2%+/-4.4%, 14.3%+/-6.6%, 13.7%+/-5.3% in the non-treated group, 19.6%+/-10.0%, 12.5%+/-6.2%, 12.0%+/-6.9% in the 2-hour hypothermia group and 12.9%+/-5.6%, 8.3%+/-3.3%, 8.2%+/-2.3% in the 3-hour hypothermia group. In the 2-hour hypothermia group, no significant size reduction was seen, but in the 3-hour hypothermia group, infarct size had decreased to half of that of the non-treated group(p<0.05). This protective effect was observed untill 1 week after MCA occlusion. rCGU in the non-treated group measured at 1 hour after MCA occlusion had increased in the periphery of the ischemic core, but at 4 hours, periischemic hypermetabolism had disappeared and the area of low metabolism in the center had become larger. rCGU in the 3-hour hypothermia group measured at 1 hour after MCA occlusion(BT 26degreesC) showed a uniform decrease in all regions, supressing temporary periischemic hypermetabolism, and at 4 hours(BT 37degreesC) after occlusion, hypermetabolism was not prominent and the area of low metabolism in the center had narrowed. This study indicates that 3 hour moderate hypothermia immediately after MCA occlusion significantly reduces infarct size, and that this protective effect was associated with suppression of periischemic hypermetabolism occurring around 1 hour after MCA occlusion.
Animals ; Brain Ischemia* ; Glucose* ; Hypothermia* ; Metabolism ; Models, Animal ; Rats*

BACKGROUND: It is well known that administration of nutrients, especially protein and amino acids mixtures, stimulates energy expenditure in the unanesthetized patients. Also, there were reports that the mechanisms for nutrient-induced thermogenesis are not impaired during general anaesthesia. The enhanced amino acid-induced thermogenesis would counteract the anaesthesia-induced reduction in metabolism and prevent the development of hypothermia. The present study was designed to see if completing the amino acid infusion before induction of anaesthesia would induce heat production, which would promote energy expenditure and thereby counteract the development of anaesthesia-induced hypothermia. METHODS: Body temperatures and arterial blood gases were measured in 48 patients during perioperative period. 24 patients had an amino acid mixture of 227 cal infused over 2 hours before anesthesia and 24 control patients received Hartman's solution. RESULTS: Amino acid infusion attenuated the development of hypothermia during the period from 60 min to 105 min after induction of anaesthesia compared to control group, however, did not prevent overall hypothermia throughout the study period. CONCLUSION: This result may indicate amino acid infusion before anesthesia can be an adjuvant to prevent intraoperative hypothermia.
Amino Acids ; Anesthesia ; Body Temperature ; Energy Metabolism ; Gases ; Humans ; Hypothermia ; Metabolism ; Perioperative Period ; Thermogenesis

OBJECTIVETo investigate the time course of calpain activity changes in rat neurons following fluid percussion injury (FPI) under normothermia (37 degrees celsius;) and mild hypothermia (32-/+0.5) degrees celsius;.

METHODSIn vitro cultured rat neurons were subjected to FPI followed by application of mild hypothermia for intervention at different time points, and the changes in intraneuronal calpain activity following FPI and the interventional effect of mild hypothermia on calpain activity were evaluated by UV-spectrophotometry at different time points.

RESULTSRemarkable changes occurred in calpain activity in the neurons following FPI at 37 degrees celsius;, and mild hypothermia produced obvious interventional effect on calpain activity in close relation to the timing of intervention initiation.

CONCLUSIONIntraneuronal calpain activity changes following FPI are involved in the pathological process of cellular injury, and mild hypothermia might offer protection against traumatic brain injury to some extent by regulating calpain activity. The interventional effect of mild hypothermia is associated with the timing of the intervention initiation.

Animals ; Calpain ; metabolism ; Female ; Hypothermia, Induced ; Neurons ; metabolism ; pathology ; Percussion ; Pregnancy ; Rats ; Rats, Wistar ; Time Factors

Brachial plexus avulsion (BPA) is a combined injury involving the central and peripheral nervous systems. Patients with BPA often experience severe neuropathic pain (NP) in the affected limb. NP is insensitive to the existing treatments, which makes it a challenge to researchers and clinicians. Accumulated evidence shows that a BPA-induced pain state is often accompanied by sympathetic nervous dysfunction, which suggests that the excitation state of the sympathetic nervous system is correlated with the existence of NP. However, the mechanism of how somatosensory neural crosstalk with the sympathetic nerve at the peripheral level remains unclear. In this study, through using a novel BPA C7 root avulsion mouse model, we found that the expression of BDNF and its receptor TrκB in the DRGs of the BPA mice increased, and the markers of sympathetic nervous system activity including α1 and α2 adrenergic receptors (α1-AR and α2-AR) also increased after BPA. The phenomenon of superexcitation of the sympathetic nervous system, including hypothermia and edema of the affected extremity, was also observed in BPA mice by using CatWalk gait analysis, an infrared thermometer, and an edema evaluation. Genetic knockdown of BDNF in DRGs not only reversed the mechanical allodynia but also alleviated the hypothermia and edema of the affected extremity in BPA mice. Further, intraperitoneal injection of adrenergic receptor inhibitors decreased neuronal excitability in patch clamp recording and reversed the mechanical allodynia of BPA mice. In another branch experiment, we also found the elevated expression of BDNF, TrκB, TH, α1-AR, and α2-AR in DRG tissues from BPA patients compared with normal human DRGs through western blot and immunohistochemistry. Our results revealed that peripheral BDNF is a key molecule in the regulation of somatosensory-sympathetic coupling in BPA-induced NP. This study also opens a novel analgesic target (BDNF) in the treatment of this pain with fewer complications, which has great potential for clinical transformation.
Humans ; Mice ; Animals ; Hyperalgesia/metabolism* ; Brain-Derived Neurotrophic Factor/metabolism* ; Hypothermia/metabolism* ; Neuralgia ; Brachial Plexus/injuries* ; Edema/metabolism*

OBJECTIVETo study the effect of mild hypothermia on glucose metabolism and glycerol of brain tissue in patients with severe traumatic brain injury (STBI) using clinical microdialysis.

METHODSThirty-one patients with STBI(GCS less than or equal to 8) were randomly divided into hypothermic group(Group A) and control group(Group B). Microdialysis catheters were inserted into the cerebral cortex of perilesional and normal brain tissue. All samples were analyzed using CMA microdialysis analyzer.

RESULTSIn comparison with the control group, lactate/glucose ratio(L/G), lactate/pyruvate ratio(L/P) and glycerol(Gly) in perilensional tissue were significantly decreased; L/P in normal brain tissue was significantly decreased. In control group, L/G, L/P and Gly in perilensional tissue were higher than that in normal brain tissue. In the hypothermic group, L/P in perilensional tissue was higher than that in relative normal brain.

CONCLUSIONSMild hypothermia protects brain tissues by decreasing L/G, L/P and Gly in perilensional tissue and L/P in "normal brain" tissues. The energy crisis and membrane phospholipid degradation in perilensional tissue are easier to happen after traumatic brain injury, and mild hypothermia protects brain better in perilensional tissue than in normal brain tissue.

Adolescent ; Adult ; Brain ; metabolism ; Brain Injuries ; metabolism ; therapy ; Glucose ; metabolism ; Glycerol ; analysis ; Humans ; Hypothermia, Induced ; methods ; Microdialysis ; Middle Aged

Isovaleric acidemia is an inborn error in metabolism due to a defect in isovaleryl-CoA dehydrogenase. Accumulation of serum isovaleric acid causes poor feeding, vomiting, lethargy, hypothermia, convulsion, mental retardation, etc. It is inherited as an autosomal recessive trait. Since the first reports of isovaleric acidemia by Tanaka et al in 1966, more than 60 cases have been reported. There are two clinically different presentations of isovaleric acidemia, with about half the patients presenting with an acute severe neonatal form and about half with a chronic intermittent forrn. The difference in clinical presentation may not be a consequence of differing severities of the causative mutation, but a result of the timing of application of catabolic stress or the ability to form isovalerylglycine. We described here clinical and organic acid analytical findings of brothers with chronic intermittent form of isovaleric acidemia. (J Korean Pediatr Soc 2000;43:828-831)
Humans ; Hypothermia ; Intellectual Disability ; Isovaleryl-CoA Dehydrogenase ; Lethargy ; Metabolism ; Seizures ; Siblings* ; Vomiting

Cerebral metabolism can be divided into basal and active metabolism. Active electroencephalogram(EEG) represents electrophysiologic activity of the brain and become flat when such an activity is abolished. Hypothermia can protect ischemic cerebral damage by reducing cerebral metabolic rate. Profound hypothermia could induce a slow or flat EEG. It can be assumed that the cessation of brain electrical activity appear far faster in the case of cerebral ischemia combined with brain cooling than simple ischemia. To prove this assumption, we carried out this study to determine if selective brain cooling shortens time to onset of a flat electroencephalogram(EEG) after cerebral ischemia. Rabbits were anesthetized with halothane and oxygen. Brain was selectively cooled by intracarotid infusion with saline at 37degrees C (normothermic group) and 18degrees C (hypothermic group). Cerebral ischemia was induced for 2 minutes with a simultaneous clamping of contralateral carotid artery and induced hypatension. In 22 of 28(79%) episodes a flat EEG was identified, and occurred an average 10+/-1 sec in the hypothermic group, 14+/-I sec in the normothermic group. Time to onset of a flat EEG was significantly faster in the hypothermic group than normothermic group(p=0.02). These pattems may be recognized as an indication of metabolic suppression of hypothermia during cerebral ischemia.
Brain Ischemia ; Brain* ; Carotid Arteries ; Constriction ; Electroencephalography* ; Halothane ; Hypothermia ; Ischemia ; Metabolism ; Oxygen ; Rabbits

BACKGROUND: Hypothermia protects the brain by suppressing the cerebral metabolism and it is performed well enough before the total circulatory arrest(TCA) in the operation of aortic disease. Generally, TCA has been performed depending on the rectal or nasopharyngeal temperatures; however, there is no definite range of optimal temperature for TCA or an objective indicator determining the temperature for safe TCA. In this study, we tried to determine the optimal range of temperature for safe hypothermic circulatory arrest by using the intraoperative electroencephalogram(EEG), and studied the role of EEG as an indicator of optimal hypothermia. MATERIAL AND METHOD: Between March, 1999 and August 31, 2000, 27 patients underwent graft replacement of the part of thoracic aorta using hypothermia and TCA with intraoperative EEG. The rectal and nasopharyngeal temperatures were monitored continuously from the time of anesthetic induction and the EEG was recorded with a ten-channel portable electroencephalography from the time of anesthetic induction to electrocerebral silence(ECS). RESULT: On ECS, the rectal and nasopharyngeal temperatures were not consistent but variable(rectal 11degree C -25degree C, nasopharynx 7.7degree C -23degree C). The correlation between two temperatures was not significant(p=0.171). The cooling time from the start of cardiopulmonary bypass to ECS was also variable(25-127min), but correlated with the body surface area(p=0.027). CONCLUSION: We have found that ECS appeared at various body temperatures, and thus, the use of rectal or nasopharyngeal temperature were not useful in identifying ECS. Conclusively, we can not fully assure cerebral protection during hypothermic circulatory arrest in regards to the body temperatures, and therefore, the intraoperative EEG is one of the necessary methods for determining the range of optimal hypothermia for safe circulatory arrest.
Aorta, Thoracic ; Aortic Diseases ; Body Temperature ; Brain ; Cardiopulmonary Bypass ; Electroencephalography* ; Humans* ; Hypothermia ; Metabolism ; Nasopharynx ; Transplants

BACKGROUNDAntegrade selective cerebral perfusion (ASCP) is regarded to perform cerebral protection during the thoracic aorta surgery as an adjunctive technique to deep hypothermic circulatory arrest (DHCA). However, brain metabolism profile after ASCP has not been systematically investigated by metabolomics technology.

METHODSTo clarify the metabolomics profiling of ASCP, 12 New Zealand white rabbits were randomly assigned into 60 min DHCA with (DHCA+ASCP [DA] group, n = 6) and without ( DHCA [D] group, n = 6) ASCP according to the random number table. ASCP was conducted by cannulation on the right subclavian artery and cross-clamping of the innominate artery. Rabbits were sacrificed 60 min after weaning off cardiopulmonary bypass. The metabolic features of the cerebral cortex were analyzed by a nontargeted metabolic profiling strategy based on gas chromatography-mass spectrometry. Variable importance projection values exceeding 1.0 were selected as potentially changed metabolites, and then Student's t-test was applied to test for statistical significance between the two groups.

RESULTSMetabolic profiling of brain was distinctive significantly between the two groups (Q 2 Y = 0.88 for partial least squares-DA model). In comparing to group D, 62 definable metabolites were varied significantly after ASCP, which were mainly related to amino acid metabolism, carbohydrate metabolism, and lipid metabolism. Kyoto Encyclopedia of Genes and Genomes analysis revealed that metabolic pathways after DHCA with ASCP were mainly involved in the activated glycolytic pathway, subdued anaerobic metabolism, and oxidative stress. In addition, L-kynurenine (P = 0.0019), 5-methoxyindole-3-acetic acid (P = 0.0499), and 5-hydroxyindole-3-acetic acid (P = 0.0495) in tryptophan metabolism pathways were decreased, and citrulline (P = 0.0158) in urea cycle was increased in group DA comparing to group D.

CONCLUSIONSThe present study applied metabolomics analysis to identify the cerebral metabolic profiling in rabbits with ASCP, and the results may shed new lights that cerebral metabolism is better preserved by ASCP compared with DHCA alone.

Animals ; Brain ; metabolism ; Cerebrovascular Circulation ; Circulatory Arrest, Deep Hypothermia Induced ; Humans ; Male ; Metabolomics ; Rabbits