Diaspirin cross-linked hemoglobin effectively restores pancreatic microcirculatory failure in hemorrhagic shock.
BACKGROUND
Microvascular reperfusion failure of splanchnic organs is a crucial hallmark in organ damage induced by hemorrhagic shock, which should be prevented by a resuscitation solution. Because the vasoactive properties of the hemoglobin-based oxygen carrier diaspirin cross-linked hemoglobin (DCLHb) could adversely influence restoration of pancreatic capillary perfusion during resuscitation, the authors investigated its effects on the microcirculation of the rat pancreas in comparison with whole blood and 6% hydroxyethylstarch resuscitation from severe hemorrhagic shock.


METHODS
Twenty-eight pentobarbital-anaesthetized rats were bled to a mean arterial pressure (MAP) of 40 mmHg and maintained at this level for 1 h. Using an intravital microscope, mean arterial pressure, the length of erythrocyte-perfused pancreatic capillaries per observation area (functional capillary density), the adherence of leukocytes in postcapillary venules, and pancreatic lipid peroxidation, measured as thiobarbituric acid-reactive material in pancreatic tissue, were determined in animals resuscitated by volumes of hydroxyethylstarch, DCLHb, and whole blood (WB) equivalent to the shed blood volume or in control animals without shock induction for a period of 2 h after resuscitation.


RESULTS
Compared with control animals (366+/-28 cm(-1)), animals resuscitated with DCLHb (294+/-45 cm(-1)), WB (306+/-11 cm(-1)), and hydroxyethylstarch (241+/-34 cm(-1)) showed a significant reduction of functional capillary density after 2 h of resuscitation. DCLHb was as effective as WB and superior to hydroxyethylstarch in restoring functional capillary density and mean arterial pressure. Leukocyte adherence in postcapillary venules was not enhanced by DCLHb (369+/-148/mm2) infusion when compared with hydroxyethylstarch- (615+/-283/mm2) and WB-treated (510+/-415/mm2) animals. Lipid peroxidation of pancreatic tissue was significantly elevated after treatment with both oxygen-carrying solutions compared with hydroxyethylstarch.


CONCLUSIONS
DCLHb is as effective as WB for preservation of the pancreatic microcirculation.
von Dobschuetz
E
E
Institute for Surgical Research, Klinikum Grosshadern Ludwig-Maximilians-University, Munich, Germany. edobschu@icf.med.uni-muenchen.de
Hoffmann
T
T
Messmer
K
K
D000136:Acid-Base Equilibrium / Q000187:drug effects; D000818:Animals; D001241:Aspirin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D001802:Blood Substitutes / Q000737:chemistry / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D003432:Cross-Linking Reagents / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D006400:Hematocrit; D006454:Hemoglobins / Q000737:chemistry / Q000494:pharmacology*; D019344:Lactic Acid / Q000097:blood; D007962:Leukocytes / Q000187:drug effects / Q000502:physiology; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D010179:Pancreas / Q000098:blood supply* / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D012771:Shock, Hemorrhagic / Q000139:chemically induced* / Q000503:physiopathology; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D001802:Blood Substitutes; D003432:Cross-Linking Reagents; D006454:Hemoglobins; D017392:Thiobarbituric Acid Reactive Substances; D019344:Lactic Acid; C030830:succinyldisalicylic acid; D001241:Aspirin