Fig. 5.
Sevoflurane (Sevo) decreases proinflammatory cytokine release, platelet–neutrophil conjugate (PNC) sequestration, and liver damage during ischemia/reperfusion (I/R) of the liver in mice. A 30-min period of liver ischemia was induced in C57BL/6 wild-type (WT) and Adora2b−/− mice. All mice were anesthetized with pentobarbital (as background anesthesia). Mice were either left as controls (without Sevo—referred to as “liver I/R WT”) or treated with Sevo (2 Vol%—referred to as “liver I/R WT + Sevo”) per inhalation. Blood and liver tissue were collected for further analysis after 3-h reperfusion. (A and B) The proinflammatory cytokines interleukin-6 (IL-6) and keratinocyte-derived chemokine (KC) were measured using cytometric bead arrays using specific allophycocyanin conjugate-Cy7 (APC-Cy7)/phycoerythrin (PE) dot plots. (C) Sevo treatment decreases the release of IL-6 after liver I/R in C57BL/6 WT mice. This effect is completely abolished in Adora2b−/− mice (n = 3 per group for WT and n = 4 for Adora2b−/−). Data are presented as scatter plots together with mean and SD imposed on the scatter. (D) Sevo decreases the release of KC after liver I/R in C57BL/6 WT and Adora2b−/− mice (n = 3 per group for WT and n = 4 for Adora2b−/−). Data are presented as scatter plots together with mean and SD imposed on the scatter. (E and F) Sevo decreases sequestration of PNCs in liver tissue after I/R in WT mice. This protective effect of Sevo was not observed in Adora2b−/− mice (n = 5 per group). (G) Sevo decreases alanine aminotransferase (ALT) release after liver I/R in WT mice. A decrease of ALT release after Sevo treatment was not observed in Adora2b−/− mice (n = 5 per group). (F and G) Data are shown as median and interquartile range. All P values are derived from the Mann–Whitney test: *P < 0.05; **P < 0.01; ***P < 0.001. n.s. = not significant.