Assessment of microvascular integrity in the isolated perfused rat liver by contrast-enhanced MRI. Attenuation of reperfusion injury by conjugated deferoxamine.
Reperfusion of an ischemic organ can lead to microcirculatory impairment caused, in part, by the generation of reactive free radicals. The iron-catalyzed formation of these deleterious substances can be counteracted by strong metal chelators like deferoxamine. In this study, the protective effect of deferoxamine conjugate was evaluated by assessment of the hepatic microcirculation in the post-ischemic phase. Assessment of the microvasculature was performed by MRI on the isolated perfused rat liver. The restriction of sinusoids subsequent to reperfusion injury was demonstrated by the use of a particulate superparamagnetic contrast agent trapped in the microvasculature. The protective effect of conjugated deferoxamine was evaluated by both MRI and release of alanine aminotransferase. Contrast-enhanced MRI demonstrated a marked impairment of the microcirculation subsequent to the unprotected reperfusion of the ischemic tissue. This injury was attenuated by deferoxamine conjugated to hydroxyethyl-starch (HES-DFO).
Department of Organic Chemistry, University of Mons-Hainaut, Belgium.
J M
JM
Colet
E
E
Cetiner
B E
BE
Hedlund
R N
RN
Muller
D000410:Alanine Transaminase / Q000032:analysis; D000818:Animals; D002614:Chelating Agents / Q000494:pharmacology* / Q000627:therapeutic use; D003676:Deferoxamine / Q000494:pharmacology* / Q000627:therapeutic use; D006895:Hydroxyethyl Starch Derivatives / Q000494:pharmacology* / Q000627:therapeutic use; D007089:Image Enhancement / Q000379:methods; D066298:In Vitro Techniques; D008099:Liver / Q000098:blood supply*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008833:Microcirculation / Q000187:drug effects*; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000175:diagnosis / Q000517:prevention & control*
D002614:Chelating Agents; D006895:Hydroxyethyl Starch Derivatives; C068460:hydroxyethyl starch-deferoxamine conjugate; D000410:Alanine Transaminase; D003676:Deferoxamine