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Histology
and Ultrastructure of Liver and Kidney Following Blood Exchange with Ultrapurified,
Polymerised Bovine Hemoglobin in Comparison with Hydroxyethyl Starch |
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Bettina Lipfert,
Thomas Standl, Jochen Düllmann, Udo Helmchen, Jochen Schulte am Esch,
and Dietrich Ernst Lorke |
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Department
of Anesthesiology (BL, TS, JSE), Anatomical Institute, Department of Neuroanatomy
(BL, JD, DEL), and Institute of Pathology (UH), University Hospital Eppendorf,
Hamburg, Germany |
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Because of their oxygen
binding capacity, cell-free hemoglobin solutions are promising blood substitutes.
However, their clinical use has so far been limited by toxic side effects
on liver and kidney until ultrapurification and chemical modifications have
been established in the production process of hemoglobin-based oxygen carriers.
The present study has been designed to examine structural changes of liver
and kidney by light and electron microscopy after complete isovolemic blood
exchange with a new ultrapurified bovine hemoglobin solution (UPBH-2) in
eight beagle dogs. The results have been compared with a sham-operated control
and eight animals having undergone blood exchange with hydroxyethyl starch
(HES), a clinically used colloidal volume substitute. In the kidney, no
changes were observed after blood exchange with UPBH-2 as compared with
the sham control. These findings indicate sufficient tissue oxygenation
and lack of renal toxicity. In contrast, histological signs of severe proximal
tubular damage, eg, wide lumina, cytoplasmic protrusions, brush-border defects,
and tubular necroses, were seen after blood exchange with HES. These changes
are consistent with hypoxic tissue damage. In the liver, a slight increase
in the number of single cell necroses was observed after UPBH-2 treatment
as well as after blood exchange with HES. At the ultrastructural level,
partial loss of microvilli and cytoplasmic protrusions of hepatocytes as
well as swelling of endothelial cells were present in both groups, but slightly
more pronounced in the UPBH-2 group. In all UPBH-2-treated animals, a marked
diminution of glycogen-granula in hepatocytes was observed indicating an
influence of UPBH-2 upon glycogen metabolism. Whereas the alterations of
hepatocytes after nearly complete blood exchange with HES can be interpreted
as a consequence of tissue hypoxia, the ultrastructural changes after UPBH-2
treatment cannot be attributed to hypoxic conditions, because improved tissue
oxygenation has been demonstrated during treatment with UPBH-2. Hepatocyte
damage was very discrete and comparable with the alterations observed after
HES treatment. Hence, major hepatotoxicity can be excluded. The absence
of significant adverse effects on the ultrastructural integrity of the kidney
indicates that UPBH-2, owing to ultrapurification and polymerization, is
an oxygen-carrying hemoglobin without acute renal toxicity. (Lab Invest,
79:573-582). |
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