Dose-Dependent Hemodynamic, Biochemical, and Tissue Oxygen Effects of OC99 following Severe Oxygen Debt Produced by Hemorrhagic Shock in Dogs.

William W Muir,Robert L Hamlin,Bradley L Youngblood,Carlos L Del Rio,Billy S H Lau,Yukie Ueyama,Robert S George,Carl W Rausch

doi:10.1155/2014/864237

William W Muir, Robert L Hamlin + Show 6 more

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https://doi.org/10.1155/2014/864237

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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.

Highlights

Hemorrhage is a major cause of morbidity and mortality in human and veterinary medicine [1, 2]
We investigated the acute dose response characteristics of a low concentration (6.5 g/dL) of highly purified polymerized bovine Hb (PBH) solution (OC99; New A Innovation Ltd., Kowloon, Hong Kong) on systemic and pulmonary arterial blood pressures, tissue oxygenation, and the metabolic correlates of oxygen debt in an experimental model of controlled hemorrhagic shock in dogs
We determined the effects of increasing circulating concentrations of a highly purified PBH (OC99) on hemodynamics, metabolic correlates of oxygen debt, and tissue oxygenation in a large animal model of controlled hemorrhagic shock

Summary

Introduction

Hemorrhage is a major cause of morbidity and mortality in human and veterinary medicine [1, 2]. Multiple animal models have established the pathophysiologic consequences of controlled and uncontrolled hemorrhage, the therapeutic importance of the timely return of normal hemodynamic values, and the restoration of microvascular perfusion [3, 4]. Evidence generated from studies conducted in large animal species (dog, pig, and humans) has identified oxygen debt and tissue oxygen-tension (tPO2) values that are predictive of both a therapeutic time window and the fluid replacement volume required to prevent irreversible shock [3, 5, 6]. Multiple cell-free hemoglobin based O2 carriers (HBOCs) and gas-carrying fluids have evolved with most demonstrating the ability to improve hemodynamics, restore tissue oxygen tension, reduce transfusion requirements, and delay definitive care compared to the administration of non-oxygen carrying crystalloids or colloids [9].

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