BACKGROUND: The aim of the study was to explore a feasible method for alleviating limb ischemia-reperfusion injury (LI/RI) through the use of a high-concentration citrate solution (HC-A solution) for limb perfusion (LP). METHODS: Eighteen pigs were divided into three groups: the Sham group, LI/RI group, and HCA group. The Sham group underwent exposure of the iliac artery and vein. The LI/RI group underwent tourniquet placement and clamping of the iliac artery and vein to simulate LI/RI. The HCA group received HC-A solution LP for 30 min through the left iliac artery below the level of blood flow occlusion based on the LI/RI group. Oxidative stress markers and inflammatory response markers were compared among the three groups. RESULTS: Compared to the LI/RI group, the HCA group showed significantly lower levels of serum creatine kinase (CK), lactate dehydrogenase (LDH), malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), aspartate aminotransferase (AST), and alanine aminotransferase (ALT), and significantly greater activities of serum superoxide dismutase (SOD) (p <
0.05). There were no significant differences in serum interleukin-6 (IL-6) or in muscle MDA, SOD, TNF-α, and IL-6 between the HCA group and the LI/RI group (p >
0.05). Compared to the LI/RI group, MDA, TNF-α, and IL-6 levels in the liver were significantly lower in the HCA group (p <
0.05), while SOD activities were not significantly different (p >
0.05). Histopathological examination revealed reduced skeletal muscle and liver damage in the HCA group compared to the LI/RI group. CONCLUSIONS: HC-A solution LP can alleviate liver damage caused by LI/RI in pigs.