Remote Ischemic Conditioning Increases Organ Injury in Murine Sepsis: Experimental Research

Remote ischemic conditioning includes the transfer of information via humoral mediators and/or neurogenic pathways from the initial remote organ exposed to the ischemia to the target organ to be protected. The postulated mechanisms of protection in the target organ involve mitochondrial adaptation to metabolic stress, redox regulation, and downregulation of many key steps leading to cell death. As possible protective mechanisms of remote ischemic conditioning and sepsis pathogenesis have so many common components, in this study, we aimed to investigate the effect of remote ischemic conditioning on survival and organ injury in cecal ligation and perforation induced (CLP) sepsis in mice. After ethical committee approval, ninety Swiss albino mice were divided into 10 groups: control group, control + ischemia group, sham group, sham + ischemia group, sham + 5h ischemia group, sham + 20h ischemia group, CLP group, CLP + ischemia group, CLP + 5h ischemia group, and CLP + 20h ischemia group. In the ischemia groups, for RIC, right hind leg was subjected to 6 cycles of 5-min ischemia and 5-min reperfusion using a surgical clamp. Antibiotics, analgesics, and fluid replacement were applied for 3 days in all groups. The organ damages were scored under light microscopy. Lung injury-related histologically findings were more prominent in CLP + 20h ischemia group than CLP, CLP + ischemia, and CLP + 5h ischemia groups. Spleen injury scores were found higher in CLP + 5h ischemia and CLP + 20h ischemia group than CLP group. Parenchymal cardiac congestion score was higher in CLP + 20h ischemia group than CLP and CLP + 5h ischemia group. The heart necrosis score was highest in CLP + 20h ischemia group. Total organ injury and every single organ injury scores were also highest in the CLP+20h ischemia group. We could not demonstrate any protective effect of remote ischemic conditioning on septic organ injury neither at early nor at late phases of sepsis. In fact, remote ischemic conditioning increased organ injury especially when applied later in cecal ligation and perforation induced sepsis in mice.