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Engineering parameters in the evaluation of hemoglobin-based blood substitutes

Posted on:1998-08-04Degree:Ph.DType:Dissertation
University:University of California, San DiegoCandidate:McCarthy, Michael RobertFull Text:PDF
GTID:1464390014977779Subject:Engineering
Abstract/Summary:
Hemoglobin based blood substitutes (HBBS) were evaluated for various physio-chemical properties which included gas transport, viscosity, and colloid osmotic pressure. The gas transport of oxygen and carbon dioxide were tested in an artificial capillary apparatus. The study examined oxygen desaturation and carbon dioxide uptake. Oxygen transport confronts to established theories for HBBS where there is greater oxygen transport compared with blood due to fewer barriers to diffusional processes. To compensate for these fewer barriers, the oxygen equilibrium curve can be shifted to the left for higher affinity and the shape of the curve altered. The HBBS with the closest transport to human red blood cells had a very low p50 with a hyperbolic shaped curve. Carbon dioxide transport was dependent on the presence of carbonic anhydrase in the solution. Transport was similar to red blood cells if the HBBS contained similar levels of catalytic activity (approximately 13,000 units). Without carbonic anhydrase, transport was decreased by a factor of 6. Mathematical modeling of the system used is discussed.; Viscosity studies were accomplished in a capillary viscometer. Most solutions tested to a low viscosity compared to blood (1.2 cP for HBBS compared with {dollar}sim{dollar}4.0 cP for whole blood). The notable exception is polyethylene glycol modified hemoglobin (PEG-Hg) which has a viscosity close to blood (3.2 for PEG-Hg). Colloid osmotic pressure (COP) of the HBBS were determined by membrane osmometry. The resultant COPs were similar to the viscosity studies with most solutions displaying low or iso-oncotic pressure. PEG-Hg was the exception with a colloid osmotic pressure 2-3 times that of blood (50-75 mmHg PEG-Hg compared with 25 mmHg blood). Representative solutions were tested using an exchange or exchange-shock protocol with rats. Parameters such as blood-gas, blood pH, blood volume, acid-base balance, and survivability were evaluated. PEG-Hg significantly outperformed all other solutions in the variables monitored. Of all the solutions tested, PEG-Hg possesses characteristics closest to that of normal blood. These characteristics included (1) most proper oxygen transport, (2) high capacity to transport carbon dioxide, (3) normal blood viscosity, (4) maintenance of blood volume.
Keywords/Search Tags:Blood, Transport, HBBS, Viscosity, Colloid osmotic pressure, Carbon dioxide
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