| Tissue oxygenation after exchange transfusion with ultrahigh-molecular-weight tense- and relaxed-state polymerized bovine hemoglobins. | |
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MedLine Citation:
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PMID: 20061539 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Hemoglobin (Hb)-based O(2) carriers (HBOCs) constitute a class of therapeutic agents designed to correct the O(2) deficit under conditions of anemia and traumatic blood loss. The O(2) transport capacity of ultrahigh-molecular-weight bovine Hb polymers (PolybHb), polymerized in the tense (T) state and relaxed (R) state, were investigated in the hamster chamber window model using microvascular measurements to determine O(2) delivery during extreme anemia. The anemic state was induced by hemodilution with a plasma expander (70-kDa dextran). After an initial moderate hemodilution to 18% hematocrit, animals were randomly assigned to exchange transfusion groups based on the type of PolybHb solution used (namely, T-state PolybHb and R-state PolybHb groups). Measurements of systemic parameters, microvascular hemodynamics, capillary perfusion, and intravascular and tissue O(2) levels were performed at 11% hematocrit. Both PolybHbs were infused at 10 g/dl, and their viscosities were higher than nondiluted blood. Restitution of the O(2) carrying capacity with T-state PolybHb exhibited lower arterial pressure and higher functional capillary density compared with R-state PolybHb. Central arterial O(2) tensions increased significantly for R-state PolybHb compared with T-state PolybHb; conversely, microvascular O(2) tensions were higher for T-state PolybHb compared with R-state PolybHb. The increased tissue Po(2) attained with T-state PolybHb results from the larger amount of O(2) released from the PolybHb and maintenance of macrovascular and microvascular hemodynamics compared with R-state PolybHb. These results suggest that the extreme high O(2) affinity of R-state PolybHb prevented O(2) bound to PolybHb from been used by the tissues. The results presented here show that T-state PolybHb, a high-viscosity O(2) carrier, is a quintessential example of an appropriately engineered O(2) carrying solution, which preserves vascular mechanical stimuli (shear stress) lost during anemic conditions and reinstates oxygenation, without the hypertensive or vasoconstriction responses observed in previous generations of HBOCs. |
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Authors:
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Pedro Cabrales; Yipin Zhou; David R Harris; Andre F Palmer |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2010-01-08 |
Journal Detail:
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Title: American journal of physiology. Heart and circulatory physiology Volume: 298 ISSN: 1522-1539 ISO Abbreviation: Am. J. Physiol. Heart Circ. Physiol. Publication Date: 2010 Mar |
Date Detail:
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Created Date: 2010-02-25 Completed Date: 2010-04-02 Revised Date: 2011-07-25 |
Medline Journal Info:
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Nlm Unique ID: 100901228 Medline TA: Am J Physiol Heart Circ Physiol Country: United States |
Other Details:
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Languages: eng Pagination: H1062-71 Citation Subset: IM |
Affiliation:
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La Jolla Bioengineering Institute, CA, USA. pcabrales@ucsd.edu |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Anemia
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drug therapy*,
metabolism Animals Blood Viscosity Cattle Cricetinae Disease Models, Animal Exchange Transfusion, Whole Blood* Hemodynamics Hemoglobins / administration & dosage, therapeutic use* Mesocricetus Molecular Weight Oxygen / metabolism* Polymers / administration & dosage, therapeutic use* |
| Grant Support | |
ID/Acronym/Agency:
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P01-HL-071064/HL/NHLBI NIH HHS; R01-DK070862/DK/NIDDK NIH HHS; R01-HL-078840/HL/NHLBI NIH HHS; R01-HL-62318/HL/NHLBI NIH HHS; R01-HL-62354/HL/NHLBI NIH HHS; R01-HL-76182/HL/NHLBI NIH HHS; R24-HL-64395/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Hemoglobins; 0/Polymers; 0/polymerized bovine hemoglobin; 7782-44-7/Oxygen |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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