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

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...

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Main Authors: William W. Muir, Carlos L. del Rio, Yukie Ueyama, Bradley L. Youngblood, Robert S. George, Carl W. Rausch, Billy S. H. Lau, Robert L. Hamlin
Format: Article
Language:English
Published: Wiley 2014-01-01
Series:Critical Care Research and Practice
Online Access:http://dx.doi.org/10.1155/2014/864237
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author William W. Muir
Carlos L. del Rio
Yukie Ueyama
Bradley L. Youngblood
Robert S. George
Carl W. Rausch
Billy S. H. Lau
Robert L. Hamlin
author_facet William W. Muir
Carlos L. del Rio
Yukie Ueyama
Bradley L. Youngblood
Robert S. George
Carl W. Rausch
Billy S. H. Lau
Robert L. Hamlin
author_sort William W. Muir
collection DOAJ
description 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.
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institution Kabale University
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publisher Wiley
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spelling doaj-art-77997e00910a41439eb915146990bd772025-02-03T01:25:07ZengWileyCritical Care Research and Practice2090-13052090-13132014-01-01201410.1155/2014/864237864237Dose-Dependent Hemodynamic, Biochemical, and Tissue Oxygen Effects of OC99 following Severe Oxygen Debt Produced by Hemorrhagic Shock in DogsWilliam W. Muir0Carlos L. del Rio1Yukie Ueyama2Bradley L. Youngblood3Robert S. George4Carl W. Rausch5Billy S. H. Lau6Robert L. Hamlin7QTest Labs, 6456 Fiesta Drive, Columbus, OH 43235, USAQTest Labs, 6456 Fiesta Drive, Columbus, OH 43235, USAQTest Labs, 6456 Fiesta Drive, Columbus, OH 43235, USAQTest Labs, 6456 Fiesta Drive, Columbus, OH 43235, USAQTest Labs, 6456 Fiesta Drive, Columbus, OH 43235, USANew A Innovation Ltd. 17/F, Chevalier Commercial Centre, 8 Wang Hoi Road, Kowloon Bay, Kowloon, Hong KongNew A Innovation Ltd. 17/F, Chevalier Commercial Centre, 8 Wang Hoi Road, Kowloon Bay, Kowloon, Hong KongQTest Labs, 6456 Fiesta Drive, Columbus, OH 43235, USAWe 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.http://dx.doi.org/10.1155/2014/864237
spellingShingle William W. Muir
Carlos L. del Rio
Yukie Ueyama
Bradley L. Youngblood
Robert S. George
Carl W. Rausch
Billy S. H. Lau
Robert L. Hamlin
Dose-Dependent Hemodynamic, Biochemical, and Tissue Oxygen Effects of OC99 following Severe Oxygen Debt Produced by Hemorrhagic Shock in Dogs
Critical Care Research and Practice
title Dose-Dependent Hemodynamic, Biochemical, and Tissue Oxygen Effects of OC99 following Severe Oxygen Debt Produced by Hemorrhagic Shock in Dogs
title_full Dose-Dependent Hemodynamic, Biochemical, and Tissue Oxygen Effects of OC99 following Severe Oxygen Debt Produced by Hemorrhagic Shock in Dogs
title_fullStr Dose-Dependent Hemodynamic, Biochemical, and Tissue Oxygen Effects of OC99 following Severe Oxygen Debt Produced by Hemorrhagic Shock in Dogs
title_full_unstemmed Dose-Dependent Hemodynamic, Biochemical, and Tissue Oxygen Effects of OC99 following Severe Oxygen Debt Produced by Hemorrhagic Shock in Dogs
title_short Dose-Dependent Hemodynamic, Biochemical, and Tissue Oxygen Effects of OC99 following Severe Oxygen Debt Produced by Hemorrhagic Shock in Dogs
title_sort dose dependent hemodynamic biochemical and tissue oxygen effects of oc99 following severe oxygen debt produced by hemorrhagic shock in dogs
url http://dx.doi.org/10.1155/2014/864237
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