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) using two different versions of arterial ligation. Version 1 (N=6) consisted of ligation/division of the right external iliac, profunda femoral and superficial femoral arteries. Version 2 (N=5) consisted of the ligation of Version 1 with additional ligation/division of the right internal iliac artery. Development of collateral pathways was evaluated with standard angiography at baseline (prior to arterial ligation) and at termination (4 weeks later).Relative luminal diameter of the arteries supplying the ischemic right hindlimb were determined by 2D angiography.Results. The dominant collateral pathway that developed after Version 1 ligation connected the right internal iliac artery to the right profunda femoral and then to the right superficial femoral/popliteal artery. Mean luminal diameter of the right internal iliac artery at termination increased by 38% compared to baseline. Two co-dominant collateral pathways developed in Version 2 ligation: (i) from the left profunda femoral artery to the reconstituted right profunda femoral artery; and (ii) from the common internal iliac trunk and the left internal iliac artery to the reconstituted right internal iliac artery, which then supplied the right profunda femoral and then the right superficial Page 3 of 29 femoral/popliteal artery. Mean diameter of the left profunda and the left internal iliac artery increased at termination by 26% and 21%, respectively (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 has value in investigation of the pathophysiology of hindlimb ischemia, and assessment of angiogenic therapies as potential treatments for PAD.