AJP - Heart Calcium Transients and Cell-Sarcomere
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Am J Physiol Heart Circ Physiol 289: H2624-H2631, 2005. First published August 5, 2005; doi:10.1152/ajpheart.00308.2005
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Is hemoglobin in hemoglobin vesicles infused for isovolemic hemodilution necessary to improve oxygenation in critically ischemic hamster skin?

Jan A. Plock,1 Claudio Contaldo,1 Hiromi Sakai,2 Eishun Tsuchida,2 Michael Leunig,1 Andrej Banic,1 Michael D. Menger,3 and Dominique Erni1

1Department of Orthopedic, Plastic and Hand Surgery, Inselspital University Hospital, Berne, Switzerland; 2Advanced Research Institute for Science and Engineering, Waseda University, Tokyo, Japan; and 3Institute for Clinical and Experimental Surgery, University of Saarland, Homburg/Saar, Germany

Submitted 30 March 2005 ; accepted in final form 31 July 2005

The aim of this study was to test the influence of hemoglobin, encapsulated in phospholipid vesicles as an oxygen carrier, given in the course of isovolemic hemodilution to improve oxygenation in critically ischemic hamster flap tissue. Capillary hemodynamics and macromolecular leakage were investigated with intravital microscopy and analyzed off-line with the CapImage software. Partial tissue oxygen tension was measured with fluorescence quenching electrodes. The occurrence of apoptosis was assessed with the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay. Vesicles with (HbV) or without (V) encapsulated Hb were suspended in 6% hydroxyethyl starch (HES) used for the 33% blood exchange. In the ischemic tissue, hemodilution led to an increase in functional capillary density by 31% for HES (P < 0.01 vs. other groups), 66% for V-HES, and 62% for HbV-HES (all P < 0.01 vs. control). Capillary diameters behaved inversely proportional to capillary microhemodynamics. The 20% increase in macromolecular leakage found over time in control animals was completely abolished in the vesicles groups (P < 0.01) but not with HES. Oxygen tension was improved from 10.7 to 16.0 mmHg after HbV-HES (P < 0.01 vs. baseline and other groups). Compared with the other groups, apoptosis was significantly reduced after HbV-HES (P < 0.01). We conclude that the encapsulation of Hb was essential to attenuate hypoxia and subsequent cell death in the critically ischemic tissue. However, the effect was partly attributed to the rheological changes exerted by the vesicles.

blood substitutes; capillary hemodynamics; hypoxia; capillary leakage; apoptosis



Address for reprint requests and other correspondence: D. Erni, Division of Plastic and Reconstructive Surgery, Inselspital Univ. Hospital, CH-3010 Berne, Switzerland (e-mail: dominique.erni{at}insel.ch)




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V. Awasthi, S.-H. Yee, P. Jerabek, B. Goins, and W. T. Phillips
Cerebral oxygen delivery by liposome-encapsulated hemoglobin: a positron-emission tomographic evaluation in a rat model of hemorrhagic shock
J Appl Physiol, July 1, 2007; 103(1): 28 - 38.
[Abstract] [Full Text] [PDF]




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