title: Dose-Dependent Hemodynamic, Biochemical, and Tissue Oxygen Effects of OC99 following Severe Oxygen Debt Produced by Hemorrhagic Shock in Dogs.
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.
authors.affiliation: QTest Labs, 6456 Fiesta Drive, Columbus, OH 43235, USA.
authors.forename: William W
authors.initials: WW
authors.lastname: Muir
authors.affiliation: QTest Labs, 6456 Fiesta Drive, Columbus, OH 43235, USA.
authors.forename: Carlos L
authors.initials: CL
authors.lastname: Del Rio
authors.affiliation: QTest Labs, 6456 Fiesta Drive, Columbus, OH 43235, USA.
authors.forename: Yukie
authors.initials: Y
authors.lastname: Ueyama
authors.affiliation: QTest Labs, 6456 Fiesta Drive, Columbus, OH 43235, USA.
authors.forename: Bradley L
authors.initials: BL
authors.lastname: Youngblood
authors.affiliation: QTest Labs, 6456 Fiesta Drive, Columbus, OH 43235, USA.
authors.forename: Robert S
authors.initials: RS
authors.lastname: George
authors.affiliation: New A Innovation Ltd. 17/F, Chevalier Commercial Centre, 8 Wang Hoi Road, Kowloon Bay, Kowloon, Hong Kong.
authors.forename: Carl W
authors.initials: CW
authors.lastname: Rausch
authors.affiliation: New A Innovation Ltd. 17/F, Chevalier Commercial Centre, 8 Wang Hoi Road, Kowloon Bay, Kowloon, Hong Kong.
authors.forename: Billy S H
authors.initials: BS
authors.lastname: Lau
authors.affiliation: QTest Labs, 6456 Fiesta Drive, Columbus, OH 43235, USA.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Hamlin