Polymerized Bovine Hemoglobin Infusion Does Not Induce Lung Damage in a Rat Model

WCU Author/Contributor (non-WCU co-authors, if there are any, appear on document)
Robert Jacobs (Creator)
Western Carolina University (WCU )
Web Site: http://library.wcu.edu/

Abstract: Establishing a hemoglobin-based oxygen carrier (HBOC) has potential to improve transfusion medicine andprovide a novel intervention to minimize tissue damage during hypoxic or ischemic insults. However, in vitro studiessuggest that HBOCs have toxic effects on endothelial cell barrier function. The purpose of this study was to determine ifthe HBOC polymerized bovine hemoglobin (PBvHb) alters pulmonary endothelial barrier function in rats duringnormoxia or hypoxia. Conscious male Sprague-Dawley rats were treated with lactated Ringer’s (LR) or PBvHb (3 ml of1.3 mg PBvHb/ml in lactated Ringer’s) and exposed to 4hr of normoxia (FiO2=21%) or hypoxia (FiO2=10%). Evans bluedye (EBD) extravasation (estimate of pulmonary vascular leak), pulmonary artery (Pa) pressure, inflammatory mediators,vascular endothelial growth factor (VEGF), fms-like tyrosine kinase-1 (sFlt-1), and hypoxia inducible factor-1 (HIF-1??)were measured in the lung and/or plasma. As expected with hypoxia, Pa pressure increased (p<0.05). PBvHb also resultedin a significant increase in Pa pressure independent of hypoxia. While a significant main effect of PBvHb on EBDextravasation was observed, no differences in inflammatory cytokines or pulmonary white blood cells existed amonggroups. No pulmonary edema was present upon assessment of wet:dry lung weights or histological examination. Hypoxiadid not influence plasma VEGF, but resulted in a small but significant increase in sFlt-1. Irrespective of hypoxia, PBvHbwas associated with increased unbound VEGF and its soluble receptor sFlt-1. However, no differences in lung VEGF orHIF-1?? were observed. We conclude that in this model, acute administration of PBvHb does not have severe overalleffects on pulmonary endothelial barrier function or inflammation.

Additional Information

Language: English
Date: 2010
Hypoxia, hemoglobin, pulmonary edema, inflammation.

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This is the peer reviewed version of the following article: Jacobs RA, Tissot van Patot MC, White MP, Foreman B, Gotshall RW, Irwin DC & Hamilton KL. (2010). Polymerized Bovine Hemoglobin Infusion Does Not Induce Lung Damage in a Rat Model. The Open Physiology Journal 3, 51-59., which has been published in final form at http://benthamopen.com/ABSTRACT/TOPHYJ-3-51The described resource is a version, edition, or adaptation of the related resource.