Defense Date

2008

Document Type

Thesis

Degree Name

Master of Science

Department

Physiology

First Advisor

Roland N. Pittman

Abstract

Hemoglobin-based oxygen carriers provide a promising future as an alternative to human blood transfusions. Hemoglobin-based oxygen carriers, HBOCs, provide a lowcost, easy to maintain, and safe solution. They require no refrigeration and are universally compatible, and the required transfusion volume is less than that of a normal transfusion. HBOCs have been known to have adverse side effects such as renal toxicity, gastrointestinal dismotility, and hypertension. Many of these problems stem from the lack of a membrane, which protects the hemoglobin from dissociating and extravasating into the blood vessel wall. Extracellular hemoglobin, like that found in HBOCs, has a greater affinity for nitric oxide, NO, than oxygen due to the lack of a protective membrane like that of a red blood cell. This NO scavenging effect has been used to explain the increase in mean arterial pressure, MAP, as well as any other smooth muscle dysfunction. NO has been accepted as the endothelial derived relaxing factor which serves to dilate or maintain the vascular tone of the arterioles. It is theorized that the drop in NO due to scavenging by hemoglobin causes an increase in MAP. In this study, using the mesentery of rats as a model to observe the microcirculation, various doses of HBOC 201, HBOC 205 (MW 400), and HBOC 205 (MW 600) were infused into the rats. Measurements of MAP and arteriolar diameter were taken in response to increasing doses of each HBOC to establish a dose-response relationship. Chemicals such as sodium nitrite, NaNO2, and Nw- Nitro-L-arginine methyl ester hydrochloride, L-NAME, a NOS inhibitor, were used to chemically alter the levels of NO. The purpose was to see if modifying the levels of NO could alter the changes in MAP due to the HBOCs. MAP rose in response to the increasing doses of HBOCs, but the arterioles failed to show any vasomotor responses. NaNO2 showed an ability to reduce the increase in MAP as a result of the HBOC, but again had no affect on arteriolar diameter. L-NAME was able to reproduce changes in MAP similar to that of the HBOCs, but again had no effect on diameter. The results support the theory of NO scavenging by the HBOC leading to an increase in MAP. The lack of activity in arterioles indicates that NO may not be a major factor in controlling vascular tone in this tissue. The results support that HBOC’s side effects are a result of NO scavenging, but further work is needed to better understand vasoactivity in the mesentery.

Rights

© The Author

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

April 2009

Included in

Physiology Commons

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