Attenuation of shock-induced hepatic microcirculatory disturbances by the use of a starch-deferoxamine conjugate for resuscitation
Bauer, M.; Feucht, K.; Ziegenfuss, T.; Marzi, I.
Critical Care Medicine 23(2): 316-322
1995
ISSN/ISBN: 0090-3493 PMID: 7532560 Document Number: 453500
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. Design: Prospective, randomized, controlled study. Setting: Laboratory at a university hospital. Subjects: Twenty-three female, inbred Lewis rats (190 to 215 g). Interventions: 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. Measurements and Main Results: Conventional resuscitation with the starch-vehicle failed to restore sinusoidal blood flow compared with either time-matched controls (71% of control value; p lt .01) or the starch-deferoxamine-treated animals (89% of control value; p lt .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/mm-2; starch-vehicle 194.5 +- 19.0/mm-2 (p lt .01 compared with controls); starch-deferoxamine conjugate 135.9 +- 12.1/mm-2 (p lt .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.