Multimodal imaging reveals transient liver metabolic disturbance and sinusoidal circulation obstruction after a single administration of ketamine/xylazine mixture

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.