Abstract:
: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.
journal_name
Am J Respir Cell Mol Biolauthors
Irwin D,Buehler PW,Alayash AI,Jia Y,Bonventura J,Foreman B,White M,Jacobs R,Piteo B,TissotvanPatot MC,Hamilton KL,Gotshall RWdoi
10.1165/rcmb.2008-0364OCsubject
Has Abstractpub_date
2010-02-01 00:00:00pages
200-9issue
2eissn
1044-1549issn
1535-4989pii
2008-0364OCjournal_volume
42pub_type
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