Department of Medical Imaging and Radiological Sciences, Chang Gung University, Taoyuan, Taiwan.
Department of Radiation Oncology, Chang Gung Memorial Hospital Linkou Branch, Taoyuan, Taiwan.
Sci Rep. 2020 Feb 27;10(1):3657. doi: 10.1038/s41598-020-60347-1.
A ketamine/xylazine (K/X) mixture is widely used before and during experiments in rodents. However, the impact of short-term use of K/X mixture and its influences on data interpretation have rarely been discussed. In this study, we administered one shot of a K/X mixture and examined acute hepatic responses using biochemical analysis, histopathological examination, and non-invasive imaging to determine the delay required prior to further assessment of the liver to avoid confounding effects triggered by anaesthesia. After the K/X injection, aspartate aminotransferase (AST) in serum was significantly elevated from 3 to 48 h. Obstructed sinusoidal circulation lasting for 24 or 36 h was revealed by DCE-MRI and drug distribution analysis, respectively. Metabolic alterations were detected at 3 h by NMR analysis and FDG-PET. Moreover, ultrasonography showed that lipid droplet accumulation increased from 1 to 16 h and declined thereafter. Taken together, our findings show that the K/X mixture induces acute hepatotoxicity and metabolic disturbance, and these disturbances cause hemodynamical disorders in the liver. The required time interval for recovery from K/X impact was dependent on the chosen assay. It took at least 16 h for metabolic recovery and 36 h for recovery of sinusoidal circulation. However, the liver was not fully recovered from the injury within 48 h.
氯胺酮/二甲噻嗪（K/X）混合物在啮齿动物实验前和实验期间被广泛使用。然而，K/X 混合物的短期使用及其对数据解释的影响很少被讨论。在这项研究中，我们给动物注射了一次 K/X 混合物，并通过生化分析、组织病理学检查和非侵入性成像来检查急性肝反应，以确定在进一步评估肝脏之前需要等待多长时间，以避免麻醉引起的混杂效应。在 K/X 注射后，血清中天冬氨酸氨基转移酶（AST）从 3 小时到 48 小时显著升高。通过 DCE-MRI 和药物分布分析分别显示阻塞性窦状循环持续 24 或 36 小时。通过 NMR 分析和 FDG-PET 在 3 小时检测到代谢改变。此外，超声检查显示，从 1 小时到 16 小时，脂滴积累增加，然后减少。总之，我们的研究结果表明，K/X 混合物引起急性肝毒性和代谢紊乱，这些紊乱导致肝脏血流动力学障碍。从 K/X 影响中恢复所需的时间间隔取决于所选的检测方法。代谢恢复至少需要 16 小时，窦状循环恢复需要 36 小时。然而，在 48 小时内，肝脏尚未从损伤中完全恢复。
