AJP - Heart Calcium Transients and Cell-Sarcomere
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Am J Physiol Heart Circ Physiol 295: H1090-H1099, 2008. First published June 20, 2008; doi:10.1152/ajpheart.00303.2008
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Polymerized bovine hemoglobin decreases oxygen delivery during normoxia and acute hypoxia in the rat

David C. Irwin,1 Ben Foreman,1 Ken Morris,1 Molly White,1,2,3 Tim Sullivan,1 Robert Jacobs,3 Eric Monnet,4 Tim Hackett,4 Martha C. TissotvanPatot,2 Karyn L. Hamilton,3 and Robert W. Gotshall3

1Cardiovascular Pulmonary Research Group, School of Medicine; 2Department of Anesthesiology, University of Colorado Health Science Center, Aurora, Colorado; 3Department of Health and Exercise Science; and 4Department of Biomedical Sciences School of Veterinary Medicine, James L. Voss Veterinary Teaching Hospital, Colorado State University, Fort Collins, Colorado

Submitted 20 March 2008 ; accepted in final form 17 June 2008

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 with the exchange transfusion models to study blood loss, less is known about HBOC oxygen delivery and vasoacitvity when it is 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 or PBvHb solution (13 g/dl, 1.3 g/kg) during acute hypoxia (FIO2 = 10%, 4 h) or normoxia (FIO2 = 21%) exposure. Our data demonstrated that compared with Ringer-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 the Ringer-infused animals treated with a nitric oxide synthase inhibitor nitro-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.

hemoglobin-based oxygen carriers; Nitric oxide; Cardiac output



Address for reprint requests and other correspondence: D. Irwin, Univ. of Colorado Health Science Center, Cardiovascular Pulmonary Research Laboratory, School of Medicine, 4200 E 9thAve., Denver, CO 80262 (e-mail: David.irwin{at}UCHSC.edu)







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