BACKGROUND/AIMS: Ischemic injury in cold preserved livers is characterized by sinusoidal endothelial cell (SEC) detachment and matrix metalloproteinase activity. Upon reperfusion reversible ischemic injury becomes permanent with SEC rapidly undergoing apoptosis. Ischemic preconditioning prevents reperfusion injury after normothermic ischemia. We hypothesized that ischemic preconditioning, through an oxygen free radical burst, protects against injury during cold preservation and reperfusion. METHODS: Ischemic preconditioning was achieved in rats by clamping blood supply to the left and median lobes for 10 min followed by 15 min of reperfusion prior to preservation in cold University of Wisconsin solution for 30 h. In a second set of experiments, rats were pretreated with N-acetyl-cysteine (NAC). SEC apoptosis upon reperfusion was assessed in an isolated perfused rat liver (IPRL) model. RESULTS: SEC detachment and activities of matrix metalloproteinase were significantly reduced in preconditioned livers. A decrease of SEC apoptosis after 1h of reperfusion in the IPRL was noted in preconditioned livers compared to controls. Pretreatment with NAC reversed the beneficial effects of ischemic preconditioning on SEC detachment and apoptosis. CONCLUSIONS: Ischemic preconditioning is an effective strategy to prevent injury during cold preservation and after reperfusion. The protective effect is possibly mediated by oxygen free radicals.
BACKGROUND/AIMS: Ischemic injury in cold preserved livers is characterized by sinusoidal endothelial cell (SEC) detachment and matrix metalloproteinase activity. Upon reperfusion reversible ischemic injury becomes permanent with SEC rapidly undergoing apoptosis. Ischemic preconditioning prevents reperfusion injury after normothermic ischemia. We hypothesized that ischemic preconditioning, through an oxygen free radical burst, protects against injury during cold preservation and reperfusion. METHODS:Ischemic preconditioning was achieved in rats by clamping blood supply to the left and median lobes for 10 min followed by 15 min of reperfusion prior to preservation in cold University of Wisconsin solution for 30 h. In a second set of experiments, rats were pretreated with N-acetyl-cysteine (NAC). SEC apoptosis upon reperfusion was assessed in an isolated perfused rat liver (IPRL) model. RESULTS: SEC detachment and activities of matrix metalloproteinase were significantly reduced in preconditioned livers. A decrease of SEC apoptosis after 1h of reperfusion in the IPRL was noted in preconditioned livers compared to controls. Pretreatment with NAC reversed the beneficial effects of ischemic preconditioning on SEC detachment and apoptosis. CONCLUSIONS:Ischemic preconditioning is an effective strategy to prevent injury during cold preservation and after reperfusion. The protective effect is possibly mediated by oxygen free radicals.
Authors: Philipp Stiegler; Michael Sereinigg; Andreas Puntschart; Andrea Bradatsch; Thomas Seifert-Held; Iris Wiederstein-Grasser; Bettina Leber; Elke Stadelmeyer; Nadia Dandachi; Siglinde Zelzer; Florian Iberer; Vanessa Stadlbauer Journal: J Transl Med Date: 2013-10-02 Impact factor: 5.531