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

Abstract

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 < .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.

• Authors: M Bauer, K Feucht, T Ziegenfuss, I Marzi
• Journal: Critical care medicine (Crit Care Med) Vol. 23 Issue 2 Pg. 316-22 (Feb 1995) ISSN: 0090-3493 [Print] United States
• PMID: 7532560 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Hydroxyethyl Starch Derivatives
• Deferoxamine

Topics

• Animals
• Cell Adhesion
• Deferoxamine (administration & dosage)
• Endothelium, Vascular (pathology)
• Female
• Hematocrit
• Hydroxyethyl Starch Derivatives (administration & dosage)
• Leukocyte Count
• Leukocytes (physiology)
• Liver Circulation
• Microcirculation
• Platelet Count
• Prospective Studies
• Random Allocation
• Rats
• Rats, Inbred Lew
• Resuscitation
• Shock, Hemorrhagic (physiopathology, therapy)