[Deferoxamine-conjugated hydroxyethyl starch reduces reperfusion injury to the liver following hemorrhagic shock].
Deferoxamine is known to reduce the iron-dependent generation of toxic oxygen-derived radicals during reperfusion of ischaemic tissue. The present study investigates the antioxidative properties of a deferoxamine-conjugated hydroxyethyl starch solution and its effects on the hepatic microcirculation in a haemorrhagic-shock rat model.


METHODS
Anaesthetized Sprague-Dawley rats were tracheotomized, prepared for invasive haemodynamic monitoring, and subject to haemorrhagic shock (MAP = 40 mmHg during 60 min). The animals were resuscitated blood-free with lactated Ringer's (RILA, n = 10), gelatin (GELA, n = 10), hydroxyethyl starch (HES, n = 10), or deferoxamine-conjugated HES (DFO, n = 8) solution (MAP > or = 70 mmHg). After 1 h of resuscitation the hepatic microcirculation was investigated by intravital microscopy, the glutathione concentration was measured in liver homogenate, and the thiobarbituric acid reactive substances (TBARS) were determined as markers of lipid peroxidation.


RESULTS
Resuscitation resulted in restoration of MAP to > or = 70 mmHg within a short time. The volume required to stabilise the arterial pressure during 1 h of resuscitation was significantly less in the DFO group compared with HES, GELA, and RILA. Significantly higher glutathione levels in liver homogenate as well as decreased TBARS levels were observed in the DFO group. The shock-induced increase of leukocyte adhesion in liver sinusoids was significantly attenuated by DFO.


CONCLUSIONS
DFO significantly attenuates shock-induced oxidative stress, thereby reducing the early inflammatory reaction and improving the hepatic microcirculation.
Bauer
C
C
Klinik für Anaesthesiologie und Intensivmedizin, Universitätskliniken des Saarlandes, Homburg/Saar.
Marzi
I
I
Larsen
R
R
D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D001810:Blood Volume / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects; D002614:Chelating Agents / Q000627:therapeutic use*; D003676:Deferoxamine / Q000627:therapeutic use*; D005260:Female; D005978:Glutathione / Q000378:metabolism; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D006895:Hydroxyethyl Starch Derivatives / Q000627:therapeutic use*; D007962:Leukocytes / Q000187:drug effects; D008102:Liver Circulation / Q000187:drug effects; D008107:Liver Diseases / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D012771:Shock, Hemorrhagic / Q000097:blood / Q000150:complications*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D013997:Time Factors
D000975:Antioxidants; D002614:Chelating Agents; D006895:Hydroxyethyl Starch Derivatives; D017392:Thiobarbituric Acid Reactive Substances; D005978:Glutathione; D003676:Deferoxamine
Deferoxamin-konjugierte Hydroxyethylstärkelösung verringert den Reperfusions-schaden der Leber nach hämorrhagischem Schock.