Chronic venous insufficiency (CVI) is a condition that occurs due to dysfunction of the venous wall and/or valves in the leg veins, making it difficult for blood to return to the heart from the legs leading to venous stasis. Blood flow from the periphery to the right atrium is referred to as venous return. This flow back to the heart against gravity during standing is facilitated by lower limb muscle contraction that compresses the local intramuscular and deep veins. This increases the intraluminal pressure that drives this venous flow while retrograde flow is prevented through the action of a system of muscular venous pumps and bicuspid valves. Here, aging and many cardiovascular diseases are related to abnormal cardiac output that may be partly due to inadequate venous return. CVI can develop because of blood clotting in the deep veins of the legs, a disease known as deep vein thrombosis (DVT), which is also known as post-thrombotic syndrome. An estimated 40 percent of people in the United States have CVI.

Improvement in venous return using electrical stimulation may be beneficial for the heart as well as blood vessels in CVI. According to the Frank-Starling law, increased blood volume in the heart facilitated by venous return can cause the cardiac muscle to contract more forcefully. Therefore, the cardiac output is synchronized with the venous return, which can be facilitated with functional electrical stimulation (FES) of the lower limb (calf) muscles. However, flow dynamics depend on the viscosity of the blood. Therefore the pulsatile frequency of the FES needs to be adapted based on blood viscosity to get a target flow rate as well as to provide for venous refilling in between the pulses. In this thesis, this was investigated based on computational flow modeling in blood vessels. Computational blood flow modeling involves simulations of the muscle--fluid--structure interactions (FSIs). We further postulate that an improvement in blood flow, e.g. assisted with FES, is beneficial for the vessel walls due to the electrokinetic vascular streaming potential that can improve endothelial function.

In this project, I also investigate the application of frequency domain (FD) near infrared spectroscopy (NIRS) to study the hemodynamics during calf muscle activity in healthy humans. The pulsatile frequency was modulated by changing the tiptoe rate, which would change the rate of calf muscle contraction that was measured using electromyogram (EMG). Based on my experimental results, I postulate that NIRS in conjunction with EMG during a tiptoe-like activity, when facilitated by EMG-triggered FES of the calf muscle, can be used to not only screen for CVI but can also improve hemodynamics---a portable theranostics application. This point of care device is currently under development and needs to be validated in the near future through a clinical study.