Journal of Applied Physiology, Vol 79, Issue 1 236-242, Copyright © 1995 by American Physiological Society

ARTICLES

Limitations of the efficacy of hemoglobin-based oxygen-carrying solutions

R. Lee, K. Neya, T. A. Svizzero and G. J. Vlahakes
Department of Surgery, Massachusetts General Hospital, Boston, USA.

Improvements in hemoglobin-based oxygen-carrying (HBOCs) solutions have overcome the toxicities that plagued earlier efforts. However, limitations of the efficacy of HBOCs are emerging. The potential limitations of an HBOC were studied in an ovine model (n = 6) of exchange transfusion. Hemodynamic, oxygen transport, and hemoglobin kinetic parameters were examined during isovolumic blood exchange to a final hematocrit of 3.2 +/- 0.7% and a plasma hemoglobin concentration of 8.1 +/- 0.4 g/dl while sheep were awake and breathing room air. However, the infusion of HBOC was associated with immediate increases in systemic and pulmonary arterial pressures. Despite hemodilution with HBOC, systemic and pulmonary vascular resistance increased 43.9% (P < 0.001) and 204.2% (P < 0.001), respectively, after HBOC infusion. After blood exchange, the plasma hemoglobin level exhibited a circulatory half-life of 52.7 +/- 18.0 h. The formation of methemoglobin was significant, accounting for 33.0 +/- 7.1% of the total circulating plasma hemoglobin at 24 h; the half-life of HBOC capable of carrying oxygen was 30.1 +/- 5.4 h. This relatively short period of oxygen-carrying efficacy and the observed vasoconstriction properties may constrain the potential applications of HBOC solutions.

This article has been cited by other articles:

				P. W. Buehler, F. D'Agnillo, V. Hoffman, and A. I. Alayash Effects of Endogenous Ascorbate on Oxidation, Oxygenation, and Toxicokinetics of Cell-Free Modified Hemoglobin after Exchange Transfusion in Rat and Guinea Pig J. Pharmacol. Exp. Ther., October 1, 2007; 323(1): 49 - 60. [Abstract] [Full Text] [PDF]

				P. Sonveaux, I. I. Lobysheva, O. Feron, and T. J. McMahon Transport and Peripheral Bioactivities of Nitrogen Oxides Carried by Red Blood Cell Hemoglobin: Role in Oxygen Delivery Physiology, April 1, 2007; 22(2): 97 - 112. [Abstract] [Full Text] [PDF]

				S. Neragi-Miandoab and G.J. Vlahakes Elevated troponin I level with hemoglobin based oxygen carrying solutions (HBOCs) as a priming solution despite improved left ventricular function Interactive CardioVascular and Thoracic Surgery, April 1, 2006; 5(2): 135 - 138. [Abstract] [Full Text] [PDF]

				I. Azarov, K. T. Huang, S. Basu, M. T. Gladwin, N. Hogg, and D. B. Kim-Shapiro Nitric Oxide Scavenging by Red Blood Cells as a Function of Hematocrit and Oxygenation J. Biol. Chem., November 25, 2005; 280(47): 39024 - 39032. [Abstract] [Full Text] [PDF]

				R. P. Rother, L. Bell, P. Hillmen, and M. T. Gladwin The Clinical Sequelae of Intravascular Hemolysis and Extracellular Plasma Hemoglobin: A Novel Mechanism of Human Disease JAMA, April 6, 2005; 293(13): 1653 - 1662. [Abstract] [Full Text] [PDF]

				X. Xu, M. Cho, N. Y. Spencer, N. Patel, Z. Huang, H. Shields, S. B. King, M. T. Gladwin, N. Hogg, and D. B. Kim-Shapiro Measurements of nitric oxide on the heme iron and {beta}-93 thiol of human hemoglobin during cycles of oxygenation and deoxygenation PNAS, September 30, 2003; 100(20): 11303 - 11308. [Abstract] [Full Text] [PDF]

				J. H. Levy, L. T. Goodnough, P. E. Greilich, G. V. S. Parr, R. W. Stewart, I. Gratz, J. Wahr, J. Williams, M. E. Comunale, D. Doblar, et al. Polymerized bovine hemoglobin solution as a replacement for allogeneic red blood cell transfusion after cardiac surgery: Results of a randomized, double-blind trial J. Thorac. Cardiovasc. Surg., July 1, 2002; 124(1): 35 - 42. [Abstract] [Full Text] [PDF]

				P. F. Moon, S. P. Bliss, L. P. Posner, H. N. Erb, and P. W. Nathanielsz Fetal Oxygen Content is Restored After Maternal Hemorrhage and Fluid Replacement with Polymerized Bovine Hemoglobin, but Not with Hetastarch, in Pregnant Sheep Anesth. Analg., July 1, 2001; 93(1): 142 - 150. [Abstract] [Full Text] [PDF]

				J. Creteur, H. Zhang, D. De Backer, Q. Sun, and J.-L. Vincent Diaspirin cross-linked hemoglobin improves oxygen extraction capabilities in endotoxic shock J Appl Physiol, October 1, 2000; 89(4): 1437 - 1444. [Abstract] [Full Text] [PDF]

				A. I. Alayash, B. A. B. Ryan, R. F. Eich, J. S. Olson, and R. E. Cashon Reactions of Sperm Whale Myoglobin with Hydrogen Peroxide. EFFECTS OF DISTAL POCKET MUTATIONS ON THE FORMATION AND STABILITY OF THE FERRYL INTERMEDIATE J. Biol. Chem., January 22, 1999; 274(4): 2029 - 2037. [Abstract] [Full Text] [PDF]

				D. W. Goldman, R. J. Breyer III, D. Yeh, B. A. Brockner-Ryan, and A. I. Alayash Acellular hemoglobin-mediated oxidative stress toward endothelium: a role for ferryl iron Am J Physiol Heart Circ Physiol, September 1, 1998; 275(3): H1046 - H1053. [Abstract] [Full Text] [PDF]

				H. G. Bone, P. J. Schenarts, S. R. Fischer, R. McGuire, L. D. Traber, and D. L. Traber Pyridoxalated hemoglobin polyoxyethylene conjugate reverses hyperdynamic circulation in septic sheep J Appl Physiol, June 1, 1998; 84(6): 1991 - 1999. [Abstract] [Full Text] [PDF]