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Erschienen in:

2013 | OriginalPaper | Buchkapitel

26. Pre-clinical Evaluation of Hemoglobin Based Oxygen Carriers: Animal Models and Biomarkers

verfasst von : Paul W. Buehler, Felice D’Agnillo

Erschienen in: Hemoglobin-Based Oxygen Carriers as Red Cell Substitutes and Oxygen Therapeutics

Verlag: Springer Berlin Heidelberg

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Abstract

The pre-clinical evaluation of hemoglobin (Hb) based oxygen carriers (HBOCs) consists of both proof of concept studies and studies to support safe use in clinical subjects. Certain HBOCs have demonstrated problematic safety profiles in human subjects, particularly in later phases of clinical trials when complicated and/or pre-existing disease states occur together. The mechanisms leading to adverse events in humans are likely related to nitric oxide (NO) interactions with Hb, but may also be associated oxidative toxicity in tissue. While the effects of NO on hypertension and vasculopathy are well established, limited data exist to support the role between Hb and oxidative tissue injury. The primary focus areas of this chapter are to (1) outline existing approaches to proof of concept studies for HBOCs and good laboratory practice (GLP) based studies to establish safe use in humans (2) suggest novel supportive approaches to pre-clinical evaluation using pre-existing disease state animal models and HBOC administration (3) propose novel markers of early tissue injury that may be beneficial in the study of HBOC safety and allow for additional understanding of human subject risk.

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Vorheriges Kapitel Ischemic Rescue with Hemoglobin-Based Oxygen Carriers

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Titel: Pre-clinical Evaluation of Hemoglobin Based Oxygen Carriers: Animal Models and Biomarkers
verfasst von: Paul W. Buehler
Felice D’Agnillo
Verlag: Springer Berlin Heidelberg
Buch: Hemoglobin-Based Oxygen Carriers as Red Cell Substitutes and Oxygen Therapeutics
Print ISBN: 978-3-642-40716-1

Electronic ISBN: 978-3-642-40717-8

Copyright-Jahr: 2013
DOI: https://doi.org/10.1007/978-3-642-40717-8_26

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