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STUDY OF DRAG REDUCING POLYMERS AND MECHANISMS OF THEIR INTRAVASCULAR EFFECT

Blood-soluble drag reducing polymers (DRPs) have been shown to produce considerable beneficial effects on blood circulation, including an increase in tissue perfusion and tissue oxygenation and a decrease in vascular resistance, when injected in blood at minute concentrations in animal models of normal and especially pathological circulation. DRPs have potential applications in treating tissue hypoperfusion caused by cardiovascular disease, stroke, peripheral vascular disease, diabetes, and other illnesses. To help to translate this novel therapy from the lab bench to the clinic, standard tests need to be developed for characterization and efficacy testing of candidate polymers. Furthermore, elucidation of the mechanisms of the observed DRP effects on blood circulation is extremely important for their future medical applications. Finally, effective, biocompatible and stable polymers which can be easily produced in large quantities must be identified. In this work a sequence of tests was developed to characterize and assess efficacy of DRPs for possible use in treating circulatory disorders. This research study also provided a better understanding of mechanical degradation of DRPs, especially in the presence of blood cells or particles. It was discovered that an increase in particle concentration led to an increase in degradation rate, and that rigid particles caused an even higher degradation rate than deformable red blood cells (RBCs). Microfluidic studies in models of microvessels showed that DRPs prevented RBC movement from the walls of microchannels toward the center and lessened plasma skimming at bifurcations, delivering more RBCs to smaller branches and thus to capillaries. In vivo, this may lead to a reduction of the near-wall plasma layer, which would facilitate gas transport, increase local wall shear stress and promote vasodilation decreasing vascular resistance in microvessels. Three polymers, including an aloe vera derived polysaccharide (AVP), poly(N-vinyl formamide), and hyaluronic acid (HA), were evaluated and characterized as new drag reducers for potential clinical use and found to be very effective. HA and AVP were found to be the most resistant to mechanical degradation of the tested polymers. Finally, relaxation time and gyration radius were found to be the polymers physical properties which best predicted their drag reducing effectiveness.

Identiferoai:union.ndltd.org:PITT/oai:PITTETD:etd-03142007-095523
Date26 June 2007
CreatorsMarhefka, Joie Nicole
ContributorsJames F. Antaki, Ph.D., Richard R. Koepsel, Ph.D., Harvey S. Borovetz, Ph.D., Toby M. Chapman, Ph.D., Marina V. Kameneva, Ph.D.
PublisherUniversity of Pittsburgh
Source SetsUniversity of Pittsburgh
LanguageEnglish
Detected LanguageEnglish
Typetext
Formatapplication/pdf
Sourcehttp://etd.library.pitt.edu/ETD/available/etd-03142007-095523/
Rightsunrestricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to University of Pittsburgh or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report.

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