Biochemical indications of cerebral ischaemia and mitochondrial dysfunction in severe brain trauma analysed with regard to type of lesion

Background: The study focuses on three questions related to the clinical usefulness of microdialysis in severe brain trauma: (1) How frequently is disturbed cerebral energy metabolism observed in various types of lesions? (2) How often does the biochemical pattern indicate cerebral ischaemia and mitochondrial dysfunction? (3) How do these patterns relate to mortality? Method: The study includes 213 consecutive patients with severe brain trauma (342 intracerebral microdialysis catheters). The patients were classified into four groups according to the type of lesion: extradural haematoma (EDH), acute subdural haematoma (SDH), cerebral haemorrhagic contusion (CHC) and no mass lesion (NML). Altogether about 150,000 biochemical analyses were performed during the initial 96 h after trauma. Results: Compromised aerobic metabolism occurred during 38 % of the study period. The biochemical pattern indicating mitochondrial dysfunction was more common than that of ischaemia. In EDH and NML aerobic metabolism was generally close to normal. In SDH or CHC it was often severely compromised. Mortality was increased in SDH with impaired aerobic metabolism, while CHC did not exhibit a similar relation. Conclusions: Compromised energy metabolism is most frequent in patients with SDH and CHC (32 % and 49 % of the study period, respectively). The biochemical pattern of mitochondrial dysfunction is more common than that of ischaemia (32 % and 6 % of the study period, respectively). A correlation between mortality and biochemical data is obtained provided the microdialysis catheter is placed in an area where energy metabolism reflects tissue outcome in a large part of the brain

Local metabolic changes in subcutaneous adipose tissue during intravenous and epidural analgesia.

BACKGROUND: This clinical study aimed at investigating the impact of postoperative thoracic epidural analgesia on extracellular glycerol concentration and glucose metabolism in subcutaneous adipose tissue, using the microdialysis technique. The sympathetic nervous activity, which can be attenuated by epidural anesthesia, influences lipolysis and the release of glycerol. METHODS: Fourteen patients who underwent major abdominal or thoraco-abdominal surgery were studied postoperatively over 3 days. For postoperative analgesia the patients were prospectively randomized to receive either thoracic epidural analgesia with a bupivacaine/morphine infusion (EPI-group, n=6) or a continuous i.v. infusion of morphine (MO-group, n=8). The concentration of glycerol, glucose and lactate in the abdominal and deltoid subcutaneous adipose tissue were measured using a microdialysis technique. RESULTS: The abdominal glycerol levels were equal in both groups. In the deltoid region of the EPI-group, glycerol concentrations started to increase on Day 2, and reached significantly higher levels on Day 3 compared with the MO-group. The glucose and lactate levels showed no differences between groups in the two regions. CONCLUSION: The uniform glycerol levels in abdominal subcutaneous adipose tissue in conjunction with the difference in glycerol levels in the deltoid area indicate that the local lipolysis is different in the two study groups. This might be explained by a regional metabolic influence of thoracic epidural analgesia, possibly via the sympathetic nervous system

Metabolism during anaesthesia and recovery in colic and healthy horses: a microdialysis study

<p>Abstract</p> <p>Background</p> <p>Muscle metabolism in horses has been studied mainly by analysis of substances in blood or plasma and muscle biopsy specimens. By using microdialysis, real-time monitoring of the metabolic events in local tissue with a minimum of trauma is possible. There is limited information about muscle metabolism in the early recovery period after anaesthesia in horses and especially in the colic horse. The aims were to evaluate the microdialysis technique as a complement to plasma analysis and to study the concentration changes in lactate, pyruvate, glucose, glycerol, and urea during anaesthesia and in the recovery period in colic horses undergoing abdominal surgery and in healthy horses not subjected to surgery.</p> <p>Methods</p> <p>Ten healthy university-owned horses given anaesthesia alone and ten client-owned colic horses subjected to emergency abdominal surgery were anaesthetised for a mean (range) of 230 min (193–273) and 208 min (145–300) respectively. Venous blood samples were taken before anaesthesia. Venous blood sampling and microdialysis in the gluteal muscle were performed during anaesthesia and until 24 h after anaesthesia. Temporal changes and differences between groups were analysed with an ANOVA for repeated measures followed by Tukey Post Hoc test or Planned Comparisons.</p> <p>Results</p> <p>Lactate, glucose and urea, in both dialysate and plasma, were higher in the colic horses than in the healthy horses for several hours after recovery to standing. In the colic horses, lactate, glucose, and urea in dialysate, and lactate in plasma increased during the attempts to stand. The lactate-to-pyruvate ratio was initially high in sampled colic horses but decreased over time. In the colic horses, dialysate glycerol concentrations varied considerably whereas in the healthy horses, dialysate glycerol was elevated during anaesthesia but decreased after standing. In both groups, lactate concentration was higher in dialysate than in plasma. The correspondence between dialysate and plasma concentrations of glucose, urea and glycerol varied.</p> <p>Conclusion</p> <p>Microdialysis proved to be suitable in the clinical setting for monitoring of the metabolic events during anaesthesia and recovery. It was possible with this technique to show greater muscle metabolic alterations in the colic horses compared to the healthy horses in response to regaining the standing position.</p

Hypoglycemia alters striatal amino acid efflux in perinatal rats: An in vivo microdialysis study

In adult brain, during insulin-induced hypoglycemia, striatal extracellular fluid concentrations of the excitatory amino acids glutamate and aspartate rise markedly (fourfold to tenfold). In this study, we used in vivo microdialysis to determine if insulin-induced hypoglycemia altered striatal amino acid efflux in similar fashion in the immature brain. Microdialysis probes were inserted into the right striatum of rats on postnatal day 7. After a 2-hour recovery period, in each animal a 30-minute baseline sample was obtained. Then insulin (0.6 Μ/Kg, intraperitoneal injection) was administered (n = 6) and dialysate sampling was continued over the next 210 minutes (terminal blood glucose level < 5 mg/dl). Untreated control rats (n = 6) were sampled over the same time interval. After pre-column derivatization with o -Phthaldialdehyde, dialysate samples were assayed by high-pressure liquid chromatography with electrochemical detection to measure their amino acid content; eight amino acids (glutamate, aspartate, taurine, glutamine, alanine, serine glycine, and asparagine) were consistently detected. In controls, amino acid efflux did not change over 4 hours. In hypoglycemic animals, glutamate efflux increased (peak: 238 ± 85% of baseline, p = 0.02, repeated measures analysis of variance [ANOVA]), glutamine efflux declined (to 44 ± 5% of baseline, P = 0.002, ANOVA), and taurine efflux increased (up to 310 ± 120% of baseline; p < 0.06, ANOVA). In contrast with 9-to 12-fold increases in aspartate efflux reported in adult striatum, asparate efflux increased only slighty (to 174 ± 69% of baseline; not significant). In immature rodent brain, overall trends in striatal amino acid efflux during hypoglycemia are similar to patterns reported in adult animals; however, there are major differences in the timing, duration, and magnitude of these responses.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/50336/1/410280408_ftp.pd

Effects of hypoxia-ischemia on monoamine metabolism in the immature brain

We measured acute changes in monoamine metabolites in corpus striatum of immature rat pups exposed to hypoxiaischemia, hypoxia alone, or total global ischemia. Carotid ligations and two hours of 8% oxygen environment in 7-day-old pups led to asymmetrical turning behavior, a 70% decrease in endogenous striatal dopamine levels, and a 125% increase in homovanillic acid (HVA) concentrations on the side of ligation. In contrast, hypoxia alone and total global ischemia alone were not associated with HVA level elevation. Elevation of HVA level with hypoxia-ischemia showed a threshold effect between 1 and 1.5 hours, and this time course paralleled that for production of gross morphological changes in rats raised to maturity. The data suggest that dopamine release from striatal nerve terminals is associated with events causing brain injury during perinatal hypoxia-ischemia. Tissue HVA in the animal model appears to be a quantitative marker for the effects of the insult on a population of nerve terminals.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/50306/1/410150407_ftp.pd