College - Author 1

College of Engineering

Department - Author 1

Biomedical and General Engineering Department

Degree Name - Author 1

BS in Biomedical Engineering



Primary Advisor

Trevor Cardinal


Peripheral arterial occlusive disease (PAOD) affects approximately 200 million individuals globally. The major underlying cause of PAOD is an inflammatory disease known as atherosclerosis, which results from the build-up of low-density lipoproteins (LDL) in the sub-intimal space. This initiates a complex cascade of events that lead to plaque growth. Plaque growth can then expand into the lumen of the vessel and result in occlusion and/or thrombosis. Symptoms of the disease can include claudication, ulcers, and/or gangrene, although many patients are asymptomatic. Similar to other forms of ischemic disease, risk factors for PAOD include hypertension, diabetes, and smoking. Common treatments include life style changes, antiplatelet therapies, and endovascular and surgical revascularization. Natural bypass surgery is a common revascularization method for patients suffering from advanced stages of PAOD. In this procedure an autologous vein segment is grafted to bypass a section of occluded artery. However, many patients experience restenosis or are unable to undergo such an invasive procedure. New therapies are needed to bridge this gap in patient care. A natural bypass is a healing mechanism that takes advantage of pre-existing vessels by enlarging them to compensate for occluded flow in another vessel. The extent to which these natural bypasses can restore the original flow rate seems to be predicated on the vascular network topology of an individual. Animal studies indicate that microvascular topologies can be either protective or vulnerable to ischemic insult from ischemic diseases, such as PAOD. Mice with highly interconnected (anastomotic) vessel networks experience faster recovery times than those with branching tree –like (dendritic) structures, likely due to compensation mechanisms from redundant supply vessels. Balb/C mice mimic dendritic architecture and experience greater ischemia and reduced hind limb functionality compared with C57BL/6 mice, which are the anastomotic archetype, following hind limb femoral artery ligation. The presence of collateral vessels in the gracilis of Balb/C mice, observed in previous work and confirmed in this study provides evidence that preexisting collaterals alone are not sufficient for improving flow. Evaluating the ability of the gracilis collateral to re-perfuse the distal hindlimb would require perfusion labeling of the endothelium, such as with lectin. The technique for perfusion labeling the gracilis muscle was demonstrated in this study. Promising results were obtained, however further optimization will be needed to improve consistency of the labeling. These findings suggest further investigation into both the nature of impaired collateral remodeling, and the continued optimization of the of lectin perfusion labeling to asses re-perfusion following arterial occlusion.