Journal of Applied Physiology Fuel your research with LabChart
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

J Appl Physiol 103: 28-38, 2007; doi:10.1152/japplphysiol.00136.2006
8750-7587/07 $8.00
This Article
Right arrow Full Text Free
Right arrow Full Text (PDF) Free
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Awasthi, V.
Right arrow Articles by Phillips, W. T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Awasthi, V.
Right arrow Articles by Phillips, W. T.

Cerebral oxygen delivery by liposome-encapsulated hemoglobin: a positron-emission tomographic evaluation in a rat model of hemorrhagic shock

Vibhudutta Awasthi,1 Seong-Hwan Yee,2 Paul Jerabek,2 Beth Goins,1 and William T. Phillips1

1Department of Radiology and 2Research Imaging Center, University of Texas Health Science Center at San Antonio, San Antonio, Texas

Submitted 22 February 2006 ; accepted in final form 16 January 2007

Liposome-encapsulated Hb (LEH) is being developed as an artificially assembled, low-toxicity, and spatially isolated Hb-based oxygen carrier (HBOC). Standard methods of evaluating oxygen carriers are based on surrogate indicators of physiology in animal models of shock. Assessment of actual delivery of oxygen by HBOCs and resultant improvement in oxygen metabolism at the tissue level has been a technical challenge. In this work, we report our findings from 15O-positron emission tomographic (15O-PET) evaluation of LEH in a rat model of 40% hypovolemic shock. In vitro studies showed that PEGylated LEH formulation containing ~7.5% Hb and consisting of neutral lipids (distearoylphosphatidylcholine:cholesterol:{alpha}-tocopherol, 51.4:46.4:2.2) efficiently picks up 15O-labeled oxygen gas. The final preparation of LEH contained 5% human serum albumin to provide oncotic pressure. Cerebral PET images of anesthetized rats inhaling 15O-labeled O2 gas showed efficient oxygen-carrying and delivery capacity of LEH formulation. From the PET images, we determined cerebral metabolic rate of oxygen (CMRO2) as a direct indicator of oxygen-carrying capacity of LEH as well as oxygen delivery and metabolism in rat brain. Compared with control fluids [saline and 5% human serum albumin (HSA)], LEH significantly improved CMRFormula to ~80% of baseline level. Saline and HSA resuscitation could not improve hypovolemia-induced decrease in CMRFormula. On the other hand, resuscitation of shed blood was the most efficient in restoring oxygen metabolism. The results suggest that 15O-PET technology can be successfully employed to evaluate potential oxygen carriers and blood substitutes and that LEH resuscitation in hemorrhage enhances oxygen delivery to the cerebral tissue and improves oxygen metabolism in brain.

oxygen carriers; blood substitutes; cerebral metabolic rate of oxygen; oxygen-15


Address for reprint requests and other correspondence: V. Awasthi, Dept. of Pharmaceutical Sciences, College of Pharmacy, Univ. of Oklahoma Health Science Center, 1110 N. Stonewall Ave., Oklahoma City, OK 73117 (e-mail: vawasthi{at}ouhsc.edu)






HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online
Copyright © 2007 by the American Physiological Society.