Variations in Surgical Procedures for Inducing Hind Limb Ischemia in Mice and the Impact of These Variations on Neovascularization Assessment

Abstract

Mouse hind limb ischemia is the most common used preclinical model for peripheral arterial disease and critical limb ischemia. This model is used to investigate the mechanisms of neovascularization and to develop new therapeutic agents. The literature shows many variations in the model, including the method of occlusion, the number of occlusions, and the position at which the occlusions are made to induce hind limb ischemia. Furthermore, predefined end points and the histopathological and radiological analysis vary. These differences hamper the correlation of results between different studies. In this review, variations in surgical methods of inducing hind limb ischemia in mice are described, and the consequences of these variations on perfusion restoration and vascular remodeling are discussed. This study aims at providing the reader with a comprehensive overview of the methods so far described, and proposing uniformity in research of hind limb ischemia in a mouse model.

Keywords: angiogenesis; animal model; arteriogenesis; hind limb ischemia; mouse.

Figure 1

Schematic diagram illustrating the hind limb ischemia and different surgical methods to induce hind limb ischemia. (A) Hind limb vasculature. (B) Single electrocoagulation of the iliac artery. (C) Single electrocoagulation of the femoral artery. (D) Double electrocoagulation of the iliac and femoral artery. Alternatively, the electrocoagulation of the iliac artery can be replaced by a second electrocoagulation of the femoral artery just above the bifurcation of the saphenous and popliteal artery. (E) Total excision of the femoral artery. Round circles are muscle groups: (Ad) adductor muscle group. (QF) Quadriceps femoris. (BF) Biceps femoris. Dotted line is the inguinal ligament. Black beam is the occlusion site.