Background—Reperfusion injury is insufficiently addressed in current clinical management of acute limb ischemia. Controlled reperfusion carries an enormous clinical potential and was tested in a new reality-driven rodent model.

Methods and Results—Acute hind-limb ischemia was induced in Wistar rats and maintained for 4 hours. Unlike previous tourniquets models, femoral vessels were surgically prepared to facilitate controlled reperfusion and to prevent venous stasis. Rats were randomized into an experimental group (n=7), in which limbs were selectively perfused with a cooled isotone heparin solution at a limited flow rate before blood flow was restored, and a conventional group (n=7; uncontrolled blood reperfusion). Rats were killed 4 hours after blood reperfusion. Nonischemic limbs served as controls. Ischemia/reperfusion injury was significant in both groups; total wet-to-dry ratio was 159±44% of normal (P=0.016), whereas muscle viability and contraction force were reduced to 65±13% (P=0.016) and 45±34% (P=0.045), respectively. Controlled reperfusion, however, attenuated reperfusion injury significantly. Tissue edema was less pronounced (132±16% versus 185±42%; P=0.011) and muscle viability (74±11% versus 57±9%; P=0.004) and contraction force (68±40% versus 26±7%; P=0.045) were better preserved than after uncontrolled reperfusion. Moreover, subsequent blood circulation as assessed by laser Doppler recovered completely after controlled reperfusion but stayed durably impaired after uncontrolled reperfusion (P=0.027).

Conclusions—Reperfusion injury was significantly alleviated by basic modifications of the initial reperfusion period in a new in vivo model of acute limb ischemia. With this model, systematic optimizations of according protocols may eventually translate into improved clinical management of acute limb ischemia.