ATTENUATION OF SHOCK-INDUCED HEPATIC MICROCIRCULATORY DISTURBANCES BYTHE USE OF A STARCH-DEFEROXAMINE CONJUGATE FOR RESUSCITATION

Objective: To determine the effects of a hydroxyethyl starch-deferoxam ine 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 h emorrhagic shock (mean arterial pressure at 40 +/- 3 mm Hg for 45 mins ) or a time-matched sham protocol, Rats in the shock groups received e ither hydroxyethyl starch or a starch-deferoxamine conjugate for resus citation. Liver microcirculation was assessed in vivo 60 mins after on set of volume therapy by epifluorescence microscopy. Measurements and Main Results: Conventional resuscitation with the starch-vehicle faile d to restore sinusoidal blood flow compared with either time-matched c ontrols (71% of control value; p < .01) or the starch-deferoxamine-tre ated animals (89% of control value; p < .05 compared with starch-vehic le), although a comparable restoration of central hemodynamics was ach ieved 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-ve hicle 194.5 +/- 19.0/mm(2) [p < .01 compared with controls]; starch-de feroxamine conjugate 135.9 +/- 12.1/mm(2) [p < .02 compared with sham and starch-vehicle]). Conclusions: Asanguineous resuscitation with con ventional hydroxyethyl starch failed to restore hepatic microvascular blood flow, despite otherwise effective resuscitation. In contrast, th e starch-deferoxamine conjugate improved volumetric blood flow and att enuated leukocyte margination in hepatic sinusoids compared with starc h-vehicle, suggesting involvement of iron-dependent, oxygen-derived ra dicals in shock-induced hepatic microcirculatory disturbances.