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Volume 125, Issue 3, Pages 815-824 (September 2003) Effects of hypothermia on brain glucose metabolism in acute liver failure: a 1H/13C- nuclear magnetic resonance study Nicolas Chatauret, Claudia Zwingmann, Christopher Rose, Dieter Leibfritz, Roger F. Butterworth Gastroenterology Volume 125, Issue 3, Pages 815-824 (September 2003) DOI: 10.1016/S0016-5085(03)01054-0

Figure 1 Labeling of metabolites from [1-13C]glucose: label distribution in glycolytic and TCA cycle intermediates during metabolism of [1-13C]glucose. A single turn of the TCA cycle from pyruvate via pyruvate carboxylase (PC) or pyruvate dehydrogenase (PDH) to 2-oxoglutarate and subsequently glutamate and glutamine is considered. A description of the pathways leading to the different isotopomers is provided in the text. LDH, lactate dehydrogenase; ALAT, alanine aminotransferase; GAD, glutamate decarboxylase; GDH, glutamate dehydrogenase; GS, glutamine synthetase. Gastroenterology 2003 125, 815-824DOI: (10.1016/S0016-5085(03)01054-0)

Figure 2 1H-NMR spectra of brain extracts in ALF: effect of hypothermia. Figure shows typical segments of 1H-NMR spectra of extracts obtained from frontal cortex of a sham-operated control rat compared with rats with ALF maintained at either 37°C (ALF-coma) or 35°C (ALF-hypothermia). Peak assignments: GABA, γ-aminobutyric acid; Glu, glutamate; Gln, glutamine; NAA, N-acetyl-aspartate; Asp, aspartate. Gastroenterology 2003 125, 815-824DOI: (10.1016/S0016-5085(03)01054-0)

Figure 3 Concentrations of brain amino acids in ALF: effect of hypothermia. Figure shows concentrations of amino acids, calculated from 1H-NMR spectra of extracts obtained from frontal cortex of sham-operated control rats (n = 6) and of rats with ALF maintained at 37°C at coma stage (n = 6) and rats with ALF maintained at 35°C (n = 6). Values represent means ± SD for n = 6 animals per group (†significantly different from sham-operated controls; ‡significantly different between hypothermic and normothermic groups; ∗∗∗P < 0.001; ∗∗P < 0.01; ∗P < 0.05; ns, not significant by ANOVA). Gastroenterology 2003 125, 815-824DOI: (10.1016/S0016-5085(03)01054-0)

Figure 4 Brain lactate synthesis in ALF: effect of hypothermia. Left: segments of 1H-NMR spectra of extracts from frontal cortex of a sham-operated control rat compared with rats with ALF maintained at 37°C (ALF coma) or 35°C (ALF hypothermia). The percentage 13C enrichment in lactate (indicating de novo synthesis) was calculated according to the formula in the upper right. Bottom, right: Changes in the concentrations, amounts of 13C-labeled lactate, and fractional 13C enrichments in lactate in rats with ALF compared with sham-operated control rats. For statistical analysis, see legend to Figure 3. Gastroenterology 2003 125, 815-824DOI: (10.1016/S0016-5085(03)01054-0)

Figure 5 13C-NMR spectra of brain extracts from rats with ALF: effect of hypothermia. Figures shows 13C-NMR spectra of extracts from frontal cortex of a sham-operated control rat compared with rats with ALF maintained at 37°C (ALF coma) or 35°C (ALF-hypothermia) 15 minutes after injection of [1-13C]glucose. Peak assignments: Ala, alanine; GABA, γ-aminobutyric acid; Glu, glutamate; Gln, glutamine; Lac, lactate; NAA, N-acetyl-aspartate (signals assigned NAA are due to naturally abundant 13C-labelled NAA). Gastroenterology 2003 125, 815-824DOI: (10.1016/S0016-5085(03)01054-0)

Figure 6 Brain alanine synthesis in ALF: effect of hypothermia. Figure shows changes in the concentration, amount of 13C-labeled alanine, and fractional 13C enrichments in alanine in frontal cortex of rats with ALF maintained at 37°C (ALF-coma) or 35°C (ALF-hypothermia) compared with sham-operated controls. For statistical analysis, see legend to Figure 3. Gastroenterology 2003 125, 815-824DOI: (10.1016/S0016-5085(03)01054-0)

Figure 7 Synthesis of brain glutamate and glutamine in ALF: effect of hypothermia. Figure shows changes in the absolute amounts of 13C (μmol/g tissue) (left) and in the percentage of 13C enrichments (right) in individual carbon positions (via the PC- and PDH pathways) of glutamate and glutamine labeled 15 minutes after injection of [1-13C]glucose, calculated from 13C-NMR spectra of extracts from frontal cortex of rats with ALF maintained at 37°C (ALF coma) or 35°C (ALF hypothermia) compared with sham-operated controls. For statistical analysis, see legend to Figure 3. Gastroenterology 2003 125, 815-824DOI: (10.1016/S0016-5085(03)01054-0)

Figure 8 Relative contribution of carbon flux through PDH and PC. Ratios of C-4/C-2 of glutamate and glutamine from 13C-NMR spectra of extracts from frontal cortex of sham-operated control rats compared with rats with ALF maintained at 37°C (ALF coma) or 35°C (ALF hypothermia). For statistical analysis, see legend to Figure 3. Gastroenterology 2003 125, 815-824DOI: (10.1016/S0016-5085(03)01054-0)