• Critical care medicine · Feb 1995

    Attenuation of shock-induced hepatic microcirculatory disturbances by the use of a starch-deferoxamine conjugate for resuscitation.

    • M Bauer, K Feucht, T Ziegenfuss, and I Marzi.
    • Clinic for Anesthesiology and Critical Care Medicine, University of Saarland, Homburg/Saar, FRG.
    • Crit. Care Med. 1995 Feb 1;23(2):316-22.

    ObjectiveTo determine the effects of a hydroxyethyl starch-deferoxamine conjugate on hepatic microcirculation in an isobaric, anesthetized rat model of hemorrhagic shock and asanguineous resuscitation.DesignProspective, randomized, controlled study.SettingLaboratory at a university hospital.SubjectsTwenty-three female, inbred Lewis rats (190 to 215 g).InterventionsAfter 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.Measurements And Main ResultsConventional 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]).ConclusionsAsanguineous 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.

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