DOI

https://doi.org/10.25772/TCP4-1R22

Defense Date

2023

Document Type

Thesis

Degree Name

Master of Science

Department

Physiology and Biophysics

First Advisor

Martin Mangino, PhD

Second Advisor

Roland Pittman, PhD

Third Advisor

Stefan Leichtle, MD

Abstract

Sepsis, a systemic immunological response that leads to organ-dysfunction, the development of septic shock, and death has mortality rate of 15-25%. A subset of sepsis, septic shock, has an in-hospital mortality rate of 30-50%. Sepsis and its treatment are the most expensive healthcare problem in the United States with the US Agency for Healthcare Research and Quality estimating annual costs over $20 billion. Hypoxia experienced in septic shock induces metabolic cell and tissue swelling leading to further microcirculatory dysfunction and poor tissue perfusion. Reversing metabolic cell swelling corrects these perfusion defects. Two models were used in rats to induce septic shock. The lipopolysaccharide infusion model and cecal ligation and puncture model. Septic shock was achieved and caused significant a reduction in microcirculatory perfusion in the ileum. Polyethylene glycol 20,000 (PEG-20K), an inert cell impermeant that moves metabolic cell water out of the cell into capillaries to improve perfusion in shock, was used and compared to treatment with lactated Ringer’s solution. Septic shock was successfully induced in both models and on OPSI observation showed a significant decrease in microcirculatory perfusion. PEG-20K caused a significant improvement in perfusion after treatment, improved survival outcomes, reduced the need for vasopressors, and improved secondary cardiovascular outcomes, relative to the LR controls. Our findings indicate that PEG-20K can serve as an efficient tool to help correct these microcirculatory deficiencies. Perfusion improvement with PEG-20K in septic shock suggests the mechanism is due, in part, to water shifts into the cell and tissue that cause compression no-reflow.

Rights

© Charles Payne

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

4-27-2023

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