Document Detail

Mixed S-nitrosylated polymerized bovine hemoglobin species moderate hemodynamic effects in acutely hypoxic rats.
MedLine Citation:
PMID:  19395680     Owner:  NLM     Status:  MEDLINE    
Hemoglobin (Hb)-based oxygen carriers (HBOCs) are being developed as a potential therapy for increasing tissue oxygenation, yet they have not reached their full potential because of unwanted hemodynamic side effects (vasoconstriction, low cardiac output, and oxygen delivery) due in part to nitric oxide (NO) scavenging by cell-free Hb. It may be possible to overcome the NO scavenging effect by coinfusing S-nitrosylated (SNO) HBOC along with unmodified HBOC. SNO-HBOC, like free Hb, may act as an NO donor in low-oxygen conditions. We hypothesized that an unaltered HBOC, polymerized bovine Hb (PBvHb), coinfused with an SNO-PBvHb, would improve hemodynamics and oxygen delivery during hypoxia. Vascular oxygen content and hemodynamics were determined after euvolemic rats were infused (3 ml) with lactated Ringer's solution, PBvHb, SNO-PBvHb, or PBvHb plus SNO-PBvHb (1:10) during normoxia or acute hypoxia (fraction of inspired oxygen = 10%, 120 min). Hemodynamic side effects resulting from PBvHb infusion (vasoconstriction, elevated pulmonary blood pressure, and reduced cardiac output) were offset by SNO-PBvHb in acute hypoxic, but not normoxic, conditions. These data support the potential use of HBOC mixed with SNO-HBOC for the treatment of conditions in which acute hypoxia is present, such as tumor oxygenation, wound healing, hemorrhagic trauma, and sickle cell and hemolytic anemia.
David Irwin; Paul W Buehler; Abdu I Alayash; Yiping Jia; Joe Bonventura; Ben Foreman; Molly White; Robert Jacobs; Brian Piteo; Martha C TissotvanPatot; Karyn L Hamilton; Robert W Gotshall
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2009-04-24
Journal Detail:
Title:  American journal of respiratory cell and molecular biology     Volume:  42     ISSN:  1535-4989     ISO Abbreviation:  Am. J. Respir. Cell Mol. Biol.     Publication Date:  2010 Feb 
Date Detail:
Created Date:  2010-01-13     Completed Date:  2010-02-01     Revised Date:  2013-06-02    
Medline Journal Info:
Nlm Unique ID:  8917225     Medline TA:  Am J Respir Cell Mol Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  200-9     Citation Subset:  IM    
University of Colorado Health Science Center, Cardiovascular Pulmonary Research Laboratory, School of Medicine, 4200 East 9th Avenue, Denver, CO 80262, USA.
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MeSH Terms
Acute Disease
Anoxia / blood,  drug therapy*,  physiopathology
Blood Pressure / drug effects
Blood Substitutes / adverse effects,  chemistry*,  pharmacology*
Cardiac Output / drug effects
Hemodynamics / drug effects*
Hemoglobins / chemistry*,  metabolism,  pharmacology*
Nitric Oxide Donors / chemistry,  pharmacology
Nitrites / blood
Nitroso Compounds / chemistry,  pharmacology
Oxygen / blood
Polymers / chemistry*,  pharmacology*
Rats, Sprague-Dawley
Vasoconstriction / drug effects
Grant Support
Reg. No./Substance:
0/Blood Substitutes; 0/Hemoglobins; 0/Nitric Oxide Donors; 0/Nitrites; 0/Nitroso Compounds; 0/Polymers; 0/polymerized bovine hemoglobin; 7782-44-7/Oxygen

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