New generation of hemoglobin-based oxygen carriers evaluated for oxygenation of critically ischemic hamster flap tissue.
OBJECTIVE
The aim of this study was to investigate and compare the effects of a traditionally formulated, low-viscosity, right-shifted polymerized bovine hemoglobin solution and a highly viscous, left-shifted hemoglobin vesicle solution (HbV-HES) on the oxygenation of critically ischemic peripheral tissue.


METHODS
Randomized, prospective study.


METHODS
University laboratory.


METHODS
A total of 40 male golden Syrian hamsters.


METHODS
Island flaps were dissected from the back skin of anesthetized hamsters. The flap included a critically ischemic, hypoxic area that was perfused via a collateralized vasculature. One hour after completion of the preparation, the animals received a 33% blood exchange with 6% hydroxyethyl starch 200/0.5 (HES, n = 9), HbV suspended in HES (HbV-HES, n = 8), or polymerized bovine hemoglobin solution (n = 9).


RESULTS
Three hours after the blood exchange, microcirculatory blood flow (laser-Doppler flowmetry) was increased to 262% of baseline for HbV-HES (p < .01) and 197% for polymerized bovine hemoglobin solution (p < .05 vs. baseline and HbV-HES). Partial tissue oxygen tension (bare fiber probes) was only improved after HbV-HES (9.4 torr to 14.2 torr, p < .01 vs. baseline and other groups). The tissue lactate/pyruvate ratio (microdialysis) was elevated to 51 in the untreated control animals, and to 34 +/- 8 after HbV-HES (p < .05 vs. control) and 38 +/- 11 after polymerized bovine hemoglobin solution (not significant).


CONCLUSIONS
Our study suggests that in critically ischemic and hypoxic collateralized peripheral tissue, oxygenation may be improved by normovolemic hemodilution with HbV-HES. We attributed this improvement to a better restoration of the microcirculation and oxygen delivery due to the formulation of the solution.
Contaldo
Claudio
C
Department of Orthopedic, Plastic, and Hand Surgery, Inselspital University Hospital, Berne, Switzerland.
Plock
Jan
J
Sakai
Hiromi
H
Takeoka
Shinji
S
Tsuchida
Eishun
E
Leunig
Michael
M
Banic
Andrej
A
Erni
Dominique
D
D000818:Animals; D001802:Blood Substitutes / Q000008:administration & dosage*; D050260:Carbohydrate Metabolism; D002417:Cattle; D006224:Cricetinae; D016638:Critical Illness; D004195:Disease Models, Animal; D004337:Drug Carriers; D005947:Glucose / Q000378:metabolism; D006438:Hemodilution / Q000379:methods; D006454:Hemoglobins / Q000008:administration & dosage / Q000378:metabolism*; D007511:Ischemia / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D019344:Lactic Acid / Q000378:metabolism; D008297:Male; D008647:Mesocricetus; D008833:Microcirculation / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D011108:Polymers / Q000008:administration & dosage; D011446:Prospective Studies; D019289:Pyruvic Acid / Q000378:metabolism; D013524:Surgical Flaps / Q000098:blood supply*; D016896:Treatment Outcome
D001802:Blood Substitutes; D004337:Drug Carriers; D006454:Hemoglobins; D011108:Polymers; C080663:polymerized bovine hemoglobin; D019344:Lactic Acid; D019289:Pyruvic Acid; D005947:Glucose; D010100:Oxygen