Remote ischemic perconditioning protects the liver from ischemia-reperfusion injury

Abstract

Background: Ischemia-reperfusion (IR)-induced injury is a frequent sequel of major liver resections. IR injury after prolonged surgical interventions could be the source of increased risk of postoperative morbidity and mortality. Hepatoprotective effects of this new feasible method called remote ischemic perconditioning (RIPER) were investigated in our rat model of IR injury.

Materials and methods: Male Wistar rats underwent ischemia for 60 min on two-thirds of their livers, followed by 1, 6, and 24 h of reperfusion (n = 72, 8 per group). During liver ischemia, but before reperfusion, rats in the treated groups received four cycles of brief infrarenal aortic clamping as perconditioning. Liver microcirculation was monitored by laser Doppler flowmeter parallel with mean arterial pressure measurements. Liver tissue injury and redox homeostasis were investigated. Furthermore, serum tumor necrosis factor alpha (TNF-α) levels were measured.

Results: In the RIPER group, compared with the IR group, serum transaminase levels were significantly lower after each reperfusion period (alanine aminotransferase: 1 h, P < 0.001; 6 h, P < 0.05; 24 h, P < 0.01 and aspartate aminotransferase: 1 h, P < 0.001; 6 h, P < 0.05; 24 h, P < 0.05). Reperfusion microcirculatory parameters significantly improved in the perconditioned group compared with those in the IR group (reperfusion area: P = 0.005; maximal plateau: P = 0.0002). Regarding TNF-α levels, significant differences were detected between the two IR injured groups (RIPER versus IR: 1 h, 34.3 ± 12.8 pg/mL versus 205.7 ± 60.9 pg/mL, P < 0.001; 6 h, 60.6 ± 11.7 pg/mL versus 110.4 ± 21.6 pg/mL, P < 0.05). Results of the histologic assessment and redox state measurements also showed favorable changes.

Conclusions: Our team firstly reported the protective effects of RIPER on liver morphology, redox homeostasis, and microcirculation and proposed the changes of TNF-α expression.

Keywords: Ischemia; Liver; Microcirculation; Perconditioning; Remote conditioning; Reperfusion; TNF-α.