Collateral development and arteriogenesis in hindlimbs of domestic swine after ligation of arterial inflow

ABSTRACT Introduction The development of collateral vasculature is a key mechanism compensating for arterial occlusions in patients with peripheral artery disease (PAD). We aimed to examine the development of collateral pathways after ligation of native vessels in a porcine model of PAD. Methods Right hindlimb Ischemia was induced in domestic swine (N=11, male, kg) using two different versions of arterial ligation. Version 1 (N=6) consisted of ligation/division of the right external iliac, profunda femoral (RPFA) and superficial femoral arteries (RSFA). Version 2 (N=5) consisted of the ligation of Version 1 with additional ligation/division of the right internal iliac artery (RIIA). Development of collateral pathways was evaluated with standard angiography at baseline (prior to arterial ligation) and at termination (4-8 weeks later). Relative luminal diameter of the arteries supplying the ischemic right hindlimb were determined by 2D angiography, as percent of the size of the distal aortic diameter. Results The dominant collateral pathway that developed after version 1 ligation connected the RIIA to the RPFA and RSFA/popliteal artery. Mean luminal diameter (± standard error) of the RIIA at termination increased by 38% (P<0.05) compared to baseline. Two co-dominant collateral pathways developed in version: (i) from the common internal iliac trunk and left internal iliac artery to the reconstituted RIIA, which then supplied the RPFA and RSFA/popliteal arteries; and (ii) from left profunda artery to the reconstituted RPFA. Mean diameter of the common internal iliac trunk and left profunda artery both increased at termination in the range of 20% (p < 0.05). Conclusion Two versions of hindlimb ischemia induction (right ilio-femoral artery ligation with and without right internal iliac artery ligation in swine produced differing collateral pathways, along with changes to the diameter of the inflow vessels (i.e., arteriogenesis). Radiographic and anatomical data of the collateral formation in this porcine model should have value in investigation of the pathophysiology of hindlimb ischemia, and assessment of angiogenic therapies as potential treatments for PAD.