All ETDs from UAB

Advisory Committee Chair

Palaniappan Sethu

Advisory Committee Members

Rajasekaran Soorappan

Prasanna Krishnamurthy

Ramasway Kannappan

Document Type

Thesis

Date of Award

2018

Degree Name by School

Master of Science in Biomedical Engineering (MSBME) School of Engineering

Abstract

Ventricular assist devices (VADs) are standard therapy for patients with advanced heart failure that is refractory to medical therapy. VADs can be categorized as pulsatile flow VADs (PF-VADs) and continuous flow VADs (CF-VADs). Both PF-VADs and CF-VADs are similarly effective in providing hemodynamic benefit and improving the quality of life and functional capacity of patients. CF-VADs are preferred over the PF-VADs due to advantages such as compact size, reliability, energy efficiency, installation and operation. However, CF-VAD support results in non-physiological diminished arterial pressure and flow pulsatility. Using the endothelial cell culture model (ECCM), we previously established that diminished pulsatility resulted in dysfunction of large vessel endothelial cells. We then obtained samples of ascending aortic tissue from patients before and after VAD implantation to validate the ECCM. We successfully identified biomarkers common between the ECCM and patient tissue which verified that elevated oxidative stress associated with reduced pulse pressure was shared across the ECCM and human patients. We then used our system to validate flow modulations that could reduce the oxidative response in endothelial cells in our ECCM. Since arterial endothelial cells are the primary transducers of pulsatility in the circulatory system, it has been hypothesized that arterial endothelial dysfunction contributes to adverse events in patients including hemorrhagic strokes, arteriovenous malformations (AVMs), compromised end-organ function, and gastrointestinal (GI) bleeding. GI bleeding was seen at a much higher rate in patients with CF-VADs versus PF-VADs. However, clinical complications due to CF-VAD usage like GI bleeding and AVMs primarily occur in small vessels. Once the ECCM was validated with in-vivo data, we evaluated production of soluble factors from large vessel endothelial cells and began investigations to determine if endothelial dysfunction in small vessels is a consequence of hemodynamics or soluble factor signaling from large vessel endothelial cells upstream.

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Engineering Commons

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