Brain lactate by magnetic resonance spectroscopy during fulminant hepatic failure in the dog

Nyberg, Scott L.; Cerra, Frank B.; Gruetter, Rolf

doi:10.1002/lt.500040203

Cited by 40 publications

(28 citation statements)

References 46 publications

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“…For example, it was previously shown that exposure of primary cultures of rat astrocytes (the cell type shown to selectively exhibit swelling in the brain in ALF) to pathophysiologically relevant concentrations of lactate leads to significant swelling.20 A recent report advocated the use of a noninvasive technique to measure brain lactate in vivo as an evaluation of advanced encephalopathy in ALF. 21 Results of the present study now show that the selective attenuation of ALF-related increases of lactate and alanine in frontal cortex, concomitant with the prevention of encephalopathy and brain edema, resides in the ability of hypothermia to prevent the de novo synthesis of lactate from glucose.…”

Section: Discussionsupporting

confidence: 55%

Effects of hypothermia on brain glucose metabolism in acute liver failure: a 1H/13C-nuclear magnetic resonance study

et al. 2003

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. Effects of hypothermia on brain glucose metabolism in acute liver failure: a H/C-nuclear magnetic resonance study. Gastroenterology, 125(3), p. ABSTRACTMild hypothermia has a protective effect on brain edema and encephalopathy in both experimental and human acute liver failure. The goals of the present study were to examine the effects of mild hypothermia (35°C) on brain metabolic pathways using combined 1 H and 13 C-Nuclear Magnetic Resonance (NMR) spectroscopy, a technique which allows the study not only of metabolite concentrations but also their de novo synthesis via cell-specific pathways in the brain. : 1 H and 13 C NMR spectroscopy using [1-13 C] glucose was performed on extracts of frontal cortex obtained from groups of rats with acute liver failure induced by hepatic devascularization whose body temperature was maintained either at 37°C (normothermic) or 35°C (hypothermic), and appropriate sham-operated controls. At coma stages of encephalopathy in the normothermic acute liver failure animals, glutamine concentrations in frontal cortex increased 3.5-fold compared to sham-operated controls (P < 0.001). Comparable increases of brain glutamine were observed in hypothermic animals despite the absence of severe encephalopathy (coma). Brain glutamate and aspartate concentrations were respectively decreased to 60.9% ± 7.7% and 42.2% ± 5.9% (P < 0.01) in normothermic animals with acute liver failure compared to control and were restored to normal values by mild hypothermia. Concentrations of lactate and alanine in frontal cortex were increased to 169.2% ± 15.6% and 267.3% ± 34.0% (P < 0.01) respectively in normothermic rats compared to controls. Furthermore, de novo synthesis of lactate and alanine increased to 446.5% ± 48.7% and 707.9% ± 65.7% (P < 0.001), of control respectively, resulting in increased fractional 13 C-enrichments in these cytosolic metabolites. Again, these changes of lactate and alanine concentrations were prevented by mild hypothermia. Mild hypothermia (35°C) prevents the encephalopathy and brain edema resulting from hepatic devascularization, selectively normalizes lactate and alanine synthesis from glucose, and prevents the impairment of oxidative metabolism associated with this model of ALF, but has no significant effect on brain glutamine. These findings suggest that a deficit in brain glucose metabolism rather than glutamine accumulation is the major cause of the cerebral complications of acute liver failure.

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Section: Discussionsupporting

confidence: 55%

Effects of hypothermia on brain glucose metabolism in acute liver failure: a 1H/13C-nuclear magnetic resonance study

et al. 2003

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“…Other mechanisms which have been proposed include impaired glucose (pyruvate) oxidation leading to brain lactate accumulation [6] and [35] and cerebral hyperemia [7], [15] and [16]. For example, a significant correlation exists between brain lactate concentrations and both encephalopathy grade [24] and [35] and EEG changes [10] in ALF. 13C-NMR studies show that mild hypothermia (35 °C), which prevents the encephalopathy and brain edema in experimental ALF, selectively normalizes brain lactate synthesis, but has no effect on glutamine synthesis.…”

Section: Discussionmentioning

confidence: 99%

Selective alterations of brain osmolytes in acute liver failure: protective effect of mild hypothermia

et al. 2004

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Zwingmann, C. et al., 2004. Selective alterations of brain osmolytes in acute liver failure: protective effect of mild hypothermia. Brain Research, 999(1), ABSTRACTThe principal cause of mortality in patients with acute liver failure (ALF) is brain herniation resulting from intracranial hypertension caused by a progressive increase of brain water. In the present study, ex vivo highresolution 1 H-NMR spectroscopy was used to investigate the effects of ALF, with or without superimposed hypothermia, on brain organic osmolyte concentrations in relation to the severity of encephalopathy and brain edema in rats with ALF due to hepatic devascularization. In normothermic ALF rats, glutamine concentrations in frontal cortex increased more than fourfold at precoma stages, i.e. prior to the onset of severe encephalopathy, but showed no further increase at coma stages. In parallel with glutamine accumulation, the brain organic osmolytes myo-inositol and taurine were significantly decreased in frontal cortex to 63% and 67% of control values, respectively, at precoma stages (p<0.01), and to 58% and 67%, respectively, at coma stages of encephalopathy (p<0.01). Hypothermia, which prevented brain edema and encephalopathy in ALF rats, significantly attenuated the depletion of myo-inositol and taurine. Brain glutamine concentrations, on the other hand, did not respond to hypothermia. These findings demonstrate that experimental ALF results in selective changes in brain organic osmolytes as a function of the degree of encephalopathy which are associated with brain edema, and provides a further rationale for the continued use of hypothermia in the management of this condition.

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“…This review discusses two of the more widely used hepatotoxins, galactosamine [29][30][31][32][33][34][35][36] and acetaminophen. [37][38][39][40][41][42][43][44] Over the past 30 years, acetaminophen overdose has become the most common cause of FHF in the United Kingdom.…”

Section: Chemical Modelsmentioning

confidence: 99%

Animal models of fulminant hepatic failure: A critical evaluation

et al. 2000

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Few conditions in medicine are more dramatic or more devastating than acute liver failure. Our understanding and treatment of this condition have been limited by the lack of satisfactory animal models. The most widely used models consist of surgical anhepatic and devascularization procedures and hepatotoxins, such as galactosamine and acetaminophen. Potential disadvantages with surgical models are their inability to recreate the inflammatory milieu that exists in acute liver failure and their reliance on surgical expertise. Models using hepatotoxins are free of such constraints. Galactosamine-induced hepatotoxicity is more predictable than acetaminophen, but its cost and lack of a human equivalent clinical syndrome has restricted its use. Acetaminophen-based models offer the greatest potential but have proven the most difficult to develop because of difficulties with reproducibility and refractory anemia. Although progress has been made, research must continue in this area to establish an animal model with minimal disadvantages that would accurately reflect the clinical syndrome seen in humans.

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Brain lactate by magnetic resonance spectroscopy during fulminant hepatic failure in the dog

Cited by 40 publications

References 46 publications

Effects of hypothermia on brain glucose metabolism in acute liver failure: a 1H/13C-nuclear magnetic resonance study

Effects of hypothermia on brain glucose metabolism in acute liver failure: a 1H/13C-nuclear magnetic resonance study

Selective alterations of brain osmolytes in acute liver failure: protective effect of mild hypothermia

Animal models of fulminant hepatic failure: A critical evaluation

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