Effects of neutrophil elastase inhibitor on flap survival after venous ischemia

Abstract

Venous ischemia is more of a threat to tissue viability than is arterial ischemia. The mechanism of injury is complex and involves many factors. Neutrophil activation is thought to be a trigger and final pathway for the tissue injury. We conducted a two-part animal study to examine the effect of neutrophil elastase inhibitor on ischemia–reperfusion injury. In the first experiment, island abdominal skin flaps were elevated in 20 rabbits (ten treated with neutrophil elastase inhibitor and ten not treated), and the pedicle vein was occluded for 6 h in both groups. Survival rates (i.e., flap survival areas) and histologic findings were compared. In the second experiment, thrombus formation was assessed in arterioles and venules injured by reactive oxygen species. Survival of the treated flaps and non-treated flaps was 91 (46–100) and 0 (0–98) %, respectively, and differed significantly (p < 0.002). Histologically, infiltration of neutrophils was observed 12 h after congestion, and severe obstruction of vessels due to thrombi was observed 48 h after congestion in the non-treatment group, but vessels were not obstructed in the treated group. Thrombi in venules contained leukocytes, but those in arterioles did not. Time to stasis in the venules in the treatment group and non-treatment group was 130.5 (96–197) and 93 (62–133) s, respectively (p < 0.01). Neutrophil elastase inhibitor was shown to maintain flap circulation and thus promote flap survival. This agent may slow thrombus formation in venules by acting on neutrophils in the venules.