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

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 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. * AAALAC : Association for Assessment and Accreditation of Laboratory Animal Care International ABI : Ankle/Brachial Index CLI : Chronic Limb Ischemia CIIT : Common Internal Iliac Trunk DICOM : Digital Imaging and Communications in Medicine dRPFA : reconstituted distal Right Profunda Femoral Artery dRIIA : reconstituted distal Right Internal Iliac Artery IACUC : Institutional Animal Care and Use Committee LEIA : Left External Iliac Artery LIIA : Left Internal Iliac Artery LPFA : Left Profunda Femoral Artery REIA : Right External Iliac Artery RLCIA : Right Lateral Circumflex Iliac RLCFA : Right Lateral Circumflex Femoral Artery RIIA : Right Internal Iliac Artery RPFA : Right Profunda Femoral Artery RSFA : Right Superficial Femoral Artery RPop : Right Popliteal Artery PAD : Peripheral Arterial Disease Moxy : Muscle Oximetry StO2 : Muscle oxygen saturation THb : Total Hemoglobin