Synergistic Effect of Ischemic Preconditioning and Antithrombin in Ischemia-Reperfusion Injury.

ABSTRACT

OBJECTIVES: Our study aimed to determine whether antithrombin plays a synergistic role in accentuating the effects of intestinal ischemic preconditioning. MATERIALS AND METHODS: Fifty rats were randomly allocated to 5 groups (10 rats/group) as follows sham treatment (group 1); ischemia-reperfusion (group 2); ischemic preconditioning followed by ischemia-reperfusion (group 3); antithrombin + ischemia-reperfusion, similar to group 2 but including antithrombin administration (group 4); and antithrombin + ischemic preconditioning, similar to group 3 but including antithrombin administration (group 5). Blood samples and liver specimens were obtained for measurement of cytokines, myeloperoxidase, and malondialdehyde. Liver biopsies were examined by electron microscopy. RESULTS: Intestinal ischemia-reperfusion induced a remote hepatic inflammatory response as evidenced by the striking increase of proinflammatory cytokines, myeloperoxidase, and malondialdehyde. Tumor necrosis factor-α levels in group 5 (12.48 ± 0.7 pg/mL) were significantly lower than in group 3 (13.64 ± 0.78 pg/mL; P = .014). Mean interleukin 1ß was lower in group 5 (9.52 ± 0.67pg/mL) than in group 3 (11.05 ± 1.9 pg/mL; P > .99). Mean interleukin 6 was also significantly lower in group 5 (17.13 ± 0.54 pg/mL) than in group 3 (23.82 ± 1 pg/mL; P ≤ .001). Myeloperoxidase levels were significantly higher in group 3 (20.52 ± 2.26 U/g) than in group 5 (18.59 ± 1.03 U/g; P = .025). However, malondialdehyde levels did not significantly improve in group 5 (4.55 ± 0.46 µmol) versus group 3 (5.17 ± 0.61 µmol; P = .286). Tumor necrosis factor-α, interleukin 6, and myeloperoxidase findings show that antithrombin administration further attenuated the inflammatory response caused by ischemia-reperfusion, suggesting a synergistic effect with ischemic preconditioning. These findings were confirmed by electron microscopy. CONCLUSIONS: The addition of antithrombin to ischemic preconditioning may act to attenuate or prevent damage from ischemia-reperfusion injury by inhibiting the release of cytokines and neutrophil infiltration.