Effects of maleimide-polyethylene glycol-modified human hemoglobin (MP4) on tissue necrosis in SKH1-hr hairless mice.
OBJECTIVE
Tissue hypoxia after blood loss, replantation and flap reperfusion remains a challenging task in surgery. Normovolemic hemodilution improves hemorheologic properties without increasing oxygen carrying capacity. Red blood cell transfusion is the current standard of treatment with its attendant risks. The aim of this study was to investigate the potential of the chemically modified hemoglobin, MP4, to reduce skin flap necrosis and its effect on selected blood markers and kidneys.


METHODS
Tissue ischemia was induced in the ear of hairless mice (n=26). Hemodilution was performed by replacing one third of blood volume with the similar amount of MP4, dextran, or blood. The extent of non-perfused tissue was assessed by intravital fluorescent microscopy.


RESULTS
Of all groups, MP4 showed the smallest area of no perfusion (in percentage of the ear +/- SEM: 16.3% +/- 2.4), the control group the largest (22.4% +/- 3.5). Leukocytes showed a significant increase in the MP4 and dextran group (from 8.7 to 13.6 respectively 15.4*109/l). On histology no changes of the kidneys could be observed.


CONCLUSIONS
MP4 causes an increase of leukocytes, improves the oxygen supply of the tissue and shows no evidence of renal impairment.
Goertz
Ole
O
Department of Plastic and Hand Surgery, Burn Center, Ruhr-University Bochum, Bochum, Germany. ole.goertz@rub.de
Kirschner
M H
MH
Lilienfein
H
H
Babilas
P
P
Steinau
H U
HU
Andree
C
C
Daigeler
A
A
Stachon
A
A
Homann
H
H
Langer
S
S
D000818:Animals; D015687:Cell Hypoxia / Q000187:drug effects*; D003911:Dextrans / Q000008:administration & dosage / Q000494:pharmacology; D004195:Disease Models, Animal; D004423:Ear / Q000098:blood supply / Q000473:pathology; D006438:Hemodilution; D006454:Hemoglobins / Q000008:administration & dosage / Q000494:pharmacology*; D007267:Injections; D007962:Leukocytes / Q000187:drug effects; D008301:Maleimides / Q000008:administration & dosage / Q000494:pharmacology*; D051379:Mice; D008812:Mice, Hairless; D009336:Necrosis / Q000188:drug therapy*; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000494:pharmacology*; D012039:Regional Blood Flow / Q000187:drug effects; D012867:Skin / Q000187:drug effects* / Q000473:pathology; D013524:Surgical Flaps / Q000473:pathology
D003911:Dextrans; D006454:Hemoglobins; D008301:Maleimides; C493836:maleimide-polyethylene glycol-modified hemoglobin, MP4; D011092:Polyethylene Glycols