A Persistent Hindlimb Ischemia Model in the Rabbit

The study of new approaches for the treatment of limb-threatening ischemia has been hampered by the lack of a suitable animal model of persistent limb ischemia. We describe the development and evaluation of an animal model of persistent hindlimb ischemia, in which ischemia was induced in the left hindlimb of 28 rabbits by ligation of the distal external iliac artery and excision of the common and superficial femoral arteries. The severity of the ischemia and its relief in each animal were evaluated every 10 days postoperatively until day 40 (all animals) or day 90 (five animals). Nine animals developed superficial tissue necrosis in the foot, but no deaths were attributable to the ischemia-inducing procedure. Angiography demonstrated minimal collateralization and sluggish filling of distal vessels up to postoperative day 90. This was accompanied by a decrease at rest in the calf blood flow ratio (p < 0.005 vs day 0), an increase in lactic acid in the femoral venous blood (left vs right side, p < 0.002) up to postoperative day 40, and a decrease in the calf blood pressure ratio (p < 0.0001 vs day 0) up to day 90. Histologic study of the gastrocnemius muscle demonstrated evidence of atrophy and fibrosis in the left hindlimb. This model can be used to evaluate direct and indirect approaches to the treatment of chronic limb ischemia.