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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2014-01-01
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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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id | doaj-art-77997e00910a41439eb915146990bd77 |
institution | Kabale University |
issn | 2090-1305 2090-1313 |
language | English |
publishDate | 2014-01-01 |
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series | Critical Care Research and Practice |
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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