Blood soluble drag reducing polymers (DRPs) represent a potential novel treatment of hypoperfusion and other disorders. Injections of these high molecular weight viscoelastic molecules into the blood of experimental animals at sub-nanomolar concentrations were shown to increase cardiac output with no changes in blood pressure (a reduction of vascular resistance) and enhance tissue perfusion and oxygenation. The DRP intravascular phenomena have been successfully utilized in animal models of various pathologies including hemorrhagic shock, hypobaric hypoxia, coronary stenosis, and diabetes. Chronic injections of DRPs demonstrated the reduction/prevention of atherosclerosis. Two reported potential mechanisms behind the DRP intravascular effects were a decrease in flow separations at vascular bifurcations and a reduction/elimination of the Fåhraeus effect (cell-free plasma layer existing in the near-vessel-wall space) in microvessels. The latter effect may enhance blood transport efficiency and selectively implement an increased shear stress on the endothelial cells in microvessels.
This work was aimed to expand the knowledge on the mechanisms behind the phenomenological effects of DRPs in the cardiovascular system and to study new biomedical applications.
A rodent model of chemically-induced diabetes illustrated the potential utility of DRPs for the improvement of microcirculation impaired by disease development and implicated as an etiology of its complications. Additional rodent experiments tested and proved the absence of acute and chronic deleterious effects of hemodynamically effective concentrations of DRPs on hematological, serum chemistry, blood gas and blood coagulation parameters. Further experiments were performed to determine the DRP concentration thresholds which could be safely used intravenously.
A hypothesis that DRPs affect RBC deformability was tested using bulk blood filtration and viscoelastometry techniques. The filterability of RBC suspensions with DRPs was found to be slightly increased reflecting a potential increase in RBC deformability. It was also shown that DRPs slightly decreased RBC viscoelasticity which was increased due to diabetes in rodents which also reflects a potential increase in RBC deformability.
Finally, DRPs were explored in tissue engineering, demonstrating that this new microhemodynamic phenomena could be employed to retard the inflammatory response to implanted biodegradable synthetic scaffolds. This resulted in enhanced collagen structure and production in tissues that replaced the scaffold material.
| Identifer | oai:union.ndltd.org:PITT/oai:PITTETD:etd-07162008-003538 |
| Date | 08 September 2008 |
| Creators | Marascalco, Philip Justin |
| Contributors | Harvey S. Borovetz, Ph.D., Richard R. Koepsel, Ph.D., James F. Antaki, Ph.D., Harry C. Blair, M.D., Marina V. Kameneva, Ph.D. |
| Publisher | University of Pittsburgh |
| Source Sets | University of Pittsburgh |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.pitt.edu/ETD/available/etd-07162008-003538/ |
| Rights | restricted, 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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