Immediate but not delayed postconditioning during reperfusion attenuates acute lung injury induced by intestinal ischemia/reperfusion in rats: comparison with ischemic preconditioning.

BACKGROUND: A previous study has shown that brief period of repetitive superior mesenteric artery (SMA) occlusion and reperfusion applied at the onset of reperfusion, ischemic postconditioning (IPo), attenuates intestinal injury after intestinal ischemia/reperfusion (II/R). This study tested the hypothesis that IPo would attenuate II/R-induced acute lung injury, which is comparable to ischemic preconditioning (IPC) and the brief period of postconditioning applied at the onset of reperfusion is critical to pulmonary protection by IPo.

METHODS: Rat II/R injury was produced by clamping SMA for 60 min followed by 60 min of reperfusion. The rats were randomly allocated into one of five groups based upon the intervention (n = 8): sham operation (Sham): sham surgical preparation including isolation of the SMA without occlusion was performed; Injury: there was no intervention either before or after SMA occlusion; ischemia preconditioning (IPC): the SMA was occluded for 10 min followed by 10 min of reperfusion before prolonged occlusion; ischemia postconditioning (IPo): three cycles of 30 sec reperfusion-30 sec reocclusion were imposed immediately upon reperfusion (3 min total intervention); delayed postconditioning: clamping was completely released for full reperfusion for 3 min (the duration of the IPo algorithm), after which three cycles of 30 sec occlusion and reperfusion were applied.

RESULTS: Histologic results showed severe damage in rat lungs in the injury group evidenced by increased lung wet/dry weight ratio and pulmonary permeability index, which was accompanied by increases in the levels of plasma TNFalpha and IL-6, the pulmonary malondialdehyde (MDA), and the pulmonary myeloperoxidase (MPO) activity and a decrease in superoxide dismutase (SOD) activity. IPo, not delayed IPo, could significantly attenuate lung injury and improve the above variables, which was comparable to IPC.

CONCLUSIONS: IPo at onset of reperfusion reduces acute lung injury induced by II/R, which may be mediated, in part, by inhibiting oxidant generation, neutrophils filtration, and proinflammatory mediators releases. The early period of reperfusion in the rat model is critical to pulmonary protection by IPo. IPo may improve outcome in clinical conditions associated with II/R.