Dose-Dependent Hemodynamic, Biochemical, and Tissue Oxygen Effects of OC99 following Severe Oxygen Debt Produced by Hemorrhagic Shock in Dogs. (27th October 2014)

• Record Type: Journal Article
• Authors: Muir, William W.; del Rio, Carlos L.; Ueyama, Yukie; Youngblood, Bradley L.; George, Robert S.; Rausch, Carl W.; Lau, Billy S. H.; Hamlin, Robert L.
• Other Names: Tisherman Samuel A. Academic Editor.
• Is Part Of: Critical care research and practice. Volume 2014(2014)
• Publication Date: 2014-10-27
• Subjects: Critical care medicine -- Periodicals; 616.028
• DOI: 10.1155/2014/864237
• Languages: English
• ISSNs: 2090-1305

Abstract

Abstract : We determined the dose-dependent effects of OC99, a novel, stabilized hemoglobin-based oxygen-carrier, on hemodynamics, systemic and pulmonary artery pressures, surrogates of tissue oxygen debt (arterial lactate 7.2 ± 0.1 mM/L and arterial base excess −17.9 ± 0.5 mM/L), and tissue oxygen tension (tPO2 ) in a dog model of controlled severe oxygen-debt from hemorrhagic shock. The dose/rate for OC99 was established from a pilot study conducted in six bled dogs. Subsequently twenty-four dogs were randomly assigned to one of four groups (n = 6 per group) and administered: 0.0, 0.065, 0.325, or 0.65 g/kg of OC99 combined with 10 mL/kg lactated Ringers solution administered in conjunction with 20 mL/kg Hextend IV over 60 minutes. The administration of 0.325 g/kg and 0.65 g/kg OC99 produced plasma hemoglobin concentrations of 0.63 ± 0.01 and 1.11 ± 0.02 g/dL, respectively, improved systemic hemodynamics, enhanced tPO2, and restored lactate and base excess values compared to 0.0 and 0.065 g/kg OC99. The administration of 0.65 g/kg OC99 significantly elevated pulmonary artery pressure. Plasma hemoglobin concentrations of OC99 ranging from 0.3 to 1.1 g/dL, in conjunction with colloid based fluid resuscitation, normalized clinical surrogates of tissue oxygen debt, improved tPO2, and avoided clinically relevant increases in pulmonary artery pressure.