Submitted on March 20, 2008
Revised on June 2, 2008
Accepted on June 17, 2008
Polymerized Bovine Hemoglobin decreases oxygen delivery during normoxia and acute hypoxia in the rat
David C Irwin1*, Ben Foreman2, Ken Morris3, Molly White4, Tim Sullivan5, Robert Jacobs6, Eric Monnet6, Tim Hackett6, Martha C Tissotvanpatot5, Karyn L Hamilton6, and Robert W. Gotshall6
1 University of Colorado HSC
2 University of colorado Health Science Center
3 University of Colorado Health science Center
4 University of Colorado Health Science Center/ Colorado State University
5 Colorado Health Science Center
6 Colorado State University
* To whom correspondence should be addressed. E-mail: david.irwin{at}uchsc.edu.
Hemoglobin based oxygen carriers (HBOC) have been primarily studied for blood loss treatment. More recently infusions of HBOC in euvolemic subjects have been proposed for a wide variety of potential therapies in which increased tissue oxygenation would be beneficial. However, compared to the exchange transfusion models to study blood loss, less is known about HBOC oxygen delivery and vasoacitvity when infused in euvolemic subjects. We hypothesized that HBOC (polymerized bovine hemoglobin, PBvHb) infusion creating hypervolemia would increase oxygen delivery to tissues during acute global hypoxia. Vascular oxygen content and hemodynamics were determined after euvolemic rats were infused with 3 ml of either lactated Ringer's or PBvHb solution (13 g/dl, 1.3g/kg) during acute hypoxia (FIO2 = 10%, 4 h) or normoxia (FIO2 = 21%) exposure. Our data demonstrated that compared to Ringer's infused animals, in hypoxia and normoxia, PBvHb treatment improved oxygen content, but raised mean arterial pressure, lowered stroke volume, heart rate, and cardiac index, which resulted in a net reduction in blood flow and oxygen delivery to the tissues. The PBvHb vasoactive effect was similar in magnitude and direction as to Ringer's infused animals treated with a nitric oxide synthase inhibitor N-L-Arginine, suggesting the PBvHb effect is mediated via nitric oxide scavenging. We conclude that infusion of PBvHb is not likely to be useful in treating global hypoxia under these conditions.
