Department of Cardiology, The Heart Centre, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark.
Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark.
Ther Hypothermia Temp Manag. 2023 Dec;13(4):208-215. doi: 10.1089/ther.2022.0065. Epub 2023 May 23.
Targeted temperature management (TTM) may moderate the injury from out-of-hospital cardiac arrest. Slowing the metabolism has been a suggested effect. Nevertheless, studies have found higher lactate levels in patients cooled to 33°C compared with 36°C even days from TTM cessation. Larger studies have not been performed on the TTM's effect on the metabolome. Accordingly, to explore the effect of TTM, we used ultra-performance liquid-mass spectrometry in a substudy of 146 patients randomized in the TTM trial to either 33°C or 36°C for 24 hours and quantified 60 circulating metabolites at the time of hospital arrival (T) and 48 hours later (T). From T to T profound changes to the metabolome were observed: tricarboxylic acid (TCA) cycle metabolites, amino acids, uric acid, and carnitine species all decreased. TTM significantly modified these changes in nine metabolites (Benjamini-Hochberg corrected false discovery rate <0.05): branched amino acids valine and leucine levels dropped more in the 33°C arm (change [95% confidence interval]: -60.9 μM [-70.8 to -50.9] vs. -36.0 μM [-45.8 to -26.3] and -35.5 μM [-43.1 to -27.8] vs. -21.2 μM [-28.7 to -13.6], respectively), whereas the TCA metabolites including malic acid and 2-oxoglutaric acid remained higher for the first 48 hours (-7.7 μM [-9.7 to -5.7] vs. -10.4 μM [-12.4 to -8.4] and -3 μM [-4.3 to -1.7] vs. -3.7 μM [-5 to -2.3]). Prostaglandin E2 only dropped in the TTM 36°C group. The results show that TTM affects the metabolism hours after normothermia have been reached. Clinical Trial Number: NCT01020916.
目标温度管理（TTM）可能会减轻院外心脏骤停引起的损伤。降低新陈代谢一直是一种被认为有效的方法。然而，即使在 TTM 停止数天后，研究发现冷却至 33°C 的患者的乳酸水平也高于冷却至 36°C 的患者。关于 TTM 对代谢组的影响，尚未进行更大规模的研究。因此，为了探索 TTM 的效果，我们在 TTM 试验的一项亚研究中使用超高效液相-质谱法对 146 名随机分为 33°C 或 36°C 组 24 小时的患者进行了研究，并在入院时（T）和 48 小时后（T）量化了 60 种循环代谢物。从 T 到 T，代谢组发生了深刻的变化：三羧酸（TCA）循环代谢物、氨基酸、尿酸和肉碱种类均减少。TTM 显著改变了其中 9 种代谢物的变化（Benjamini-Hochberg 校正假发现率<0.05）：支链氨基酸缬氨酸和亮氨酸的水平在 33°C 组下降更多（变化[95%置信区间]：-60.9μM[-70.8 至-50.9] vs. -36.0μM[-45.8 至-26.3] 和-35.5μM[-43.1 至-27.8] vs. -21.2μM[-28.7 至-13.6]），而包括苹果酸和 2-氧戊二酸在内的 TCA 代谢物在前 48 小时内仍保持较高水平（-7.7μM[-9.7 至-5.7] vs. -10.4μM[-12.4 至-8.4] 和-3μM[-4.3 至-1.7] vs. -3.7μM[-5 至-2.3]）。前列腺素 E2 仅在 TTM 36°C 组下降。结果表明，在达到正常体温数小时后，TTM 会影响代谢。临床试验编号：NCT01020916。
