Couffinal et al. were among the fir

Couffinal et al. were among the first to describe a mouse model for hind limb ischemia [576]. They induced acute hind limb ischemia by ligating the proximal end of the femoral artery, and the distal portion of the saphenous artery, followed by excision of ligated part of the femoral artery and attached side branches. The recovery of blood flow in the ischemic limb due to angiogenesis and arteriogenesis was monitored by laser Doppler perfusion imaging (LDPI) [576], Fig. 25. Subsequently, many groups used similar approaches and variants of this model [577, 578]. Surgical procedures range from a single ligation of the femoral or iliac artery [579–581] to a complete excision of the artery [576] and sometimes even the vein and the nerve were dissected as well [582, 583]. Several excellent review papers have been written on these variations in the hind limb ischemia model [584–587]. When choosing a particular variant of the mouse hind limb ischemia model for a study, it is important to define the goal of the study. For instance, when testing new pro-arteriogenic approaches, there should be an appropriate therapeutic window in which an improvement of blood flow recovery can be monitored. In mice that rapidly form new collaterals, for example, C57BL/6 mice with a single ligation of the femoral artery, it is difficult to monitor an increase toward an even faster collateral formation [588], and therefore a model with more severe injury is required [589, 590]. On the other hand, such a fast model is ideal for mechanistic studies in which the effects of the deficiency or inhibition of crucial factors on blood flow recovery are studied [591, 592]. The fast recovery model is also associated with less animal discomfort.