Attenuation of shock-induced hepatic microcirculatory disturbances by the use of a starch-deferoxamine conjugate for resuscitation.
OBJECTIVE
To determine the effects of a hydroxyethyl starch-deferoxamine conjugate on hepatic microcirculation in an isobaric, anesthetized rat model of hemorrhagic shock and asanguineous resuscitation.


METHODS
Prospective, randomized, controlled study.


METHODS
Laboratory at a university hospital.


METHODS
Twenty-three female, inbred Lewis rats (190 to 215 g).


METHODS
After anesthesia (pentobarbital-sodium; 50 mg/kg), tracheotomy, and cannulation, animals were assigned to a hemorrhagic shock (mean arterial pressure at 40 +/- 3 mm Hg for 45 mins) or a time-matched sham protocol. Rats in the shock groups received either hydroxyethyl starch or a starch-deferoxamine conjugate for resuscitation. Liver microcirculation was assessed in vivo 60 mins after onset of volume therapy by epifluorescence microscopy.


RESULTS
Conventional resuscitation with the starch-vehicle failed to restore sinusoidal blood flow compared with either time-matched controls (71% of control value; p < .01) or the starch-deferoxamine-treated animals (89% of control value; p < .05 compared with starch-vehicle), although a comparable restoration of central hemodynamics was achieved with both starch preparations. Additionally, treatment with the starch-deferoxamine conjugate resulted in a significant attenuation of sinusoidal leukocyte margination (sham 72.4 +/- 11.0/mm2; starch-vehicle 194.5 +/- 19.0/mm2 [p < .01 compared with controls]; starch-deferoxamine conjugate 135.9 +/- 12.1/mm2 [p < .02 compared with sham and starch-vehicle]).


CONCLUSIONS
Asanguineous resuscitation with conventional hydroxyethyl starch failed to restore hepatic microvascular blood flow, despite otherwise effective resuscitation. In contrast, the starch-deferoxamine conjugate improved volumetric blood flow and attenuated leukocyte margination in hepatic sinusoids compared with starch-vehicle, suggesting involvement of iron-dependent, oxygen-derived radicals in shock-induced hepatic microcirculatory disturbances.
Bauer
M
M
Clinic for Anesthesiology and Critical Care Medicine, University of Saarland, Homburg/Saar, FRG.
Feucht
K
K
Ziegenfuss
T
T
Marzi
I
I
D000818:Animals; D002448:Cell Adhesion; D003676:Deferoxamine / Q000008:administration & dosage*; D004730:Endothelium, Vascular / Q000473:pathology; D005260:Female; D006400:Hematocrit; D006895:Hydroxyethyl Starch Derivatives / Q000008:administration & dosage*; D007958:Leukocyte Count; D007962:Leukocytes / Q000502:physiology; D008102:Liver Circulation; D008833:Microcirculation; D010976:Platelet Count; D011446:Prospective Studies; D011897:Random Allocation; D051381:Rats; D011917:Rats, Inbred Lew; D012151:Resuscitation; D012771:Shock, Hemorrhagic / Q000503:physiopathology / Q000628:therapy*
D006895:Hydroxyethyl Starch Derivatives; D003676:Deferoxamine