Date

8-2013

Degree Name

BS in Biomedical Engineering

Department

Biomedical and General Engineering Department

Advisor(s)

Trevor Cardinal

Abstract

Peripheral arterial occlusive disease (PAOD) is a globally prevalent cardiovascular disease in which atherosclerotic plaques narrow arterial lumen diameters and restrict blood flow to down stream tissues. The impact of these occlusions can be mitigated by collateral vessels that connect parallel arterial branches and act as natural bypasses to maintain perfusion. Some patients with PAOD may not have robust collateral networks to accommodate ischemic tissues in the event of an occlusion and, therefore, may be more susceptible to hypoxia and tissue necrosis. In animal models that lack collateral arterioles, capillaries can arterialize and form functional collaterals; however, in the early stages of development, they do not exhibit functional vasodilation in response to muscle contraction. We explored the mechanism of impaired functional vasodilation in arterialized capillaries by testing endothelial-dependent vasodilation (acetylcholine), endothelial-independent vasodilation (sodium nitroprusside), and endothelial-independent vasoconstriction (norepinephrine). First, we performed pilot studies to generate dose response curves to each of these agents in spinotrapezius arterioles. The optimal concentration that produced the most robust vascular responses was 10-5 M for all three agents. In the following study, the spinotrapezius feed artery was ligated in Balb/C mice, a strain that lacks native collaterals, to stimulate the development of arterialized capillaries and determine their vascular reactivity. Although vasodilation and vasoconstriction in arterialized capillaries seven days post-surgery were impaired compared to terminal arterioles of similar size in unoperated animals, the vessel diameter changes were still significant. The comparable impairment in both endothelial-dependent and endothelial-independent vasodilation indicates that vascular smooth muscle cells are still developing, rearranging, or both, and are not yet fully capable of regulating diameter in immature arterialized capillaries. Identifying factors that improve the functionality of smooth muscle cells in the arterialized capillaries may be applied to improve patient prognosis during ischemic events in vasculature lacking pre-existing collaterals.

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