J Korean Med Sci.  2024 Feb;39(7):e79. 10.3346/jkms.2024.39.e79.

Differences in Brain Metabolite Profiles Between Normothermia and Hypothermia

• Sohn SH
• Chae S
• Choi JW
• Nam K
• Cho YJ
• Cho JY
• Hwang HY

• KMID: 2553319
• DOI: http://doi.org/10.3346/jkms.2024.39.e79

Abstract

Background
This study evaluated the difference in brain metabolite profiles between normothermia and hypothermia reaching 25°C in humans in vivo.
Methods
Thirteen patients who underwent thoracic aorta surgery under moderate hypothermia were prospectively enrolled. Plasma samples were collected simultaneously from the arteries and veins to estimate metabolite uptake or release. Targeted metabolomics based on liquid chromatographic mass spectrometry and direct flow injection were performed, and changes in the profiles of respective metabolites from normothermia to hypothermia were compared. The ratios of metabolite concentrations in venous blood samples to those in arterial blood samples (V/A ratios) were calculated, and log 2 transformation of the ratios [log₂ (V/A)] was performed for comparison between the temperature groups.
Results
Targeted metabolomics were performed for 140 metabolites, including 20 amino acids, 13 biogenic amines, 10 acylcarnitines, 82 glycerophospholipids, 14 sphingomyelins, and 1 hexose. Of the 140 metabolites analyzed, 137 metabolites were released from the brain in normothermia, and the release of 132 of these 137 metabolites was decreased in hypothermia. Two metabolites (dopamine and hexose) showed constant release from the brain in hypothermia, and 3 metabolites (2 glycophospholipids and 1 sphingomyelin) showed conversion from release to uptake in hypothermia. Glutamic acid demonstrated a distinct brain metabolism in that it was taken up by the brain in normothermia, and the uptake was increased in hypothermia.
Conclusion
Targeted metabolomics demonstrated various degrees of changes in the release of metabolites by the hypothermic brain. The release of most metabolites was decreased in hypothermia, whereas glutamic acid showed a distinct brain metabolism.

Keyword

Hypothermia; Metabolomics; Aorta Surgery; Glutamic Acid

Figure

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  Fig. 1 Illustration of the sample collection process. (A) The brain is mainly perfused by both internal carotid arteries and vertebral arteries, and the metabolites supplied to the brain were assumed to be identical to those collected at the right radial artery. (B) The metabolites released from the brain are mainly drained to the internal jugular vein, and the metabolites produced by the brain were assumed to be identical to those collected at the left internal jugular vein. (C) A short intravenous catheter for sampling from the internal jugular vein was placed as shown.

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  Fig. 2 Unlike most of the other metabolites that showed decreased release in hypothermia, the release of 2 metabolites (dopamine and hexose) from the brain was not decreased but was constant in hypothermia.

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  Fig. 3 Unlike most the of other metabolites that showed decreased release in hypothermia, the release of 3 metabolites (phosphatidylcholine ae C42:4, phosphatidylcholine ae C42:5, and sphingomyelin C26:0) from the brain changed to uptake by the brain in hypothermia.

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  Fig. 4 Distinct brain metabolism of glutamic acid. It was taken up by the brain in normothermia, and the uptake was increased in hypothermia.

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  Fig. 5 To evaluate the difference in the brain metabolite profile between normothermia and hypothermia reaching 25°C, we performed targeted metabolomics of the hypothermic human brain in vivo. Thirteen patients who underwent thoracic aorta surgery under moderate hypothermia were prospectively enrolled, and 140 metabolites were analyzed for each patient. The study results demonstrated various degrees of changes in the release of metabolites by the hypothermic brain. In most metabolites, the release was decreased in hypothermia, whereas glutamic acid showed a distinct brain metabolism of increased uptake in hypothermia.

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