The Effect of C1 Esterase Inhibitor on Ischemic Reperfusion Injury in Rat Epigastric Skin Flaps: Preliminary Results

Introduction: In free tissue transfer and replantations, restored blood flow following a prolonged ischemic period may lead to tissue damage as a result of ischemia reperfusion injury. Several studies have shown that the complement system plays an important role in the pathogenesis of ischemic reperfusion injury. C1 esterase inhibitor prevents complement activation during ischemia reperfusion injury by targeting the classical and lecitin pathways. The purpose of this study was to evaluate the effect of C1 esterase inhibitor on flap survival, using an inferior epigastric artery skin flap as a flap ischemia reperfusion injury model.

Methodology and Material: Epigastric island skin flaps were elevated in 50 rats. The rats were randomly divided in 5 groups. Group 0 was the sham group and did not undergo ischemic insult. In groups 1 to 4, primary global ischemia of 8 hours was performed. Group 1 (control group) underwent primary ischemia without any therapeutic intervention. Group 2 was subjected to an ischemic preconditioning protocol (3 cycles of 10 minutes of repeated ischemia/reperfusion periods) prior to primary ischemia. In group 3, we used intravenous administration of C1 esterase inhibitor 5 minutes before reperfusion. And in group 4, we combined both ischemic preconditioning technique and C1 esterase inhibitor infusion.

Results: The preliminary results of our study have shown that the mean surviving flap areas of groups 0, 1, 2, 3 and 4 were 100%, 94´1%, 98%, 97´1% and 98,2% respectively. Our study showed a slightly higher survival rate in the intervention groups (groups 2, 3 and 4) than group 1 (control) and lower survival rate than group 0 (sham), with no statistical differences (p > 0,05).

Conclusions: According to the preliminary results, none of our treatments (the ischemic preconditioning protocol, the C1 esterase inhibitor administration or the combined therapy) had statistically significant effect on flap survival. Histological and biochemical assays might be useful to confirm our macroscopic results.