Mixed S-nitrosylated polymerized bovine hemoglobin species moderate hemodynamic effects in acutely hypoxic rats.
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.
Irwin
David
D
University of Colorado Health Science Center, Cardiovascular Pulmonary Research Laboratory, School of Medicine, 4200 East 9th Avenue, Denver, CO 80262, USA. david.irwin@uchsc.edu
Buehler
Paul W
PW
Alayash
Abdu I
AI
Jia
Yiping
Y
Bonventura
Joe
J
Foreman
Ben
B
White
Molly
M
Jacobs
Robert
R
Piteo
Brian
B
TissotvanPatot
Martha C
MC
Hamilton
Karyn L
KL
Gotshall
Robert W
RW
D000208:Acute Disease; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001802:Blood Substitutes / Q000009:adverse effects / Q000737:chemistry* / Q000494:pharmacology*; D002302:Cardiac Output / Q000187:drug effects; D002417:Cattle; D006439:Hemodynamics / Q000187:drug effects*; D006454:Hemoglobins / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D000860:Hypoxia / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D020030:Nitric Oxide Donors / Q000737:chemistry / Q000494:pharmacology; D009573:Nitrites / Q000097:blood; D009603:Nitroso Compounds / Q000737:chemistry / Q000494:pharmacology; D010100:Oxygen / Q000097:blood; D011108:Polymers / Q000737:chemistry* / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014661:Vasoconstriction / Q000187:drug effects
D001802:Blood Substitutes; D006454:Hemoglobins; D020030:Nitric Oxide Donors; D009573:Nitrites; D009603:Nitroso Compounds; D011108:Polymers; C080663:polymerized bovine hemoglobin; D010100:Oxygen