Prevention of post-ischemic brain lipid conjugated diene production and neurological injury by hydroxyethyl starch-conjugated deferoxamine.
Hydroxyethyl starch conjugated deferoxamine (DFO) was administered to rats following resuscitation from 6.5 min cardiac arrest (CA) in an attempt to prevent the iron-catalyzed production of oxygen free radicals which may lead to neurologic injury and ultimately death following restoration of spontaneous circulation (ROSC). Brain conjugated dienes were analyzed spectrophotometrically 4 and 24 hr following ROSC, and were found to be significantly elevated when compared to non-ischemic controls. Hydroxyethyl starch-DFO treated rats demonstrated no increased conjugated diene production at either period. Neurologic injury was significantly less in drug treated rats surviving 24 or 72 hours when compared to controls. While mortality was similar in drug treated or control rats for the first 24 hours following ROSC, delayed mortality (days 1-10) was significantly less in drug treated animals, presumably as a result of neurologic protection afforded by post-ischemic drug administration. Administration of DFO conjugated to hydroxyethyl starch appears to modulate the neurologic injury which occurs during brain ischemia and reperfusion.
Rosenthal
R E
RE
Department of Emergency Medicine, George Washington University Medical Center, Washington, D.C. 20037.
Chanderbhan
R
R
Marshall
G
G
Fiskum
G
G
D000475:Alkenes / Q000378:metabolism; D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D003676:Deferoxamine / Q000494:pharmacology*; D005609:Free Radicals; D006323:Heart Arrest / Q000378:metabolism; D006895:Hydroxyethyl Starch Derivatives / Q000494:pharmacology*; D007502:Iron Chelating Agents / Q000494:pharmacology; D015227:Lipid Peroxidation; D008054:Lipid Peroxides / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D008297:Male; D008970:Molecular Weight; D051381:Rats; D011919:Rats, Inbred Strains
D000475:Alkenes; D005609:Free Radicals; D006895:Hydroxyethyl Starch Derivatives; D007502:Iron Chelating Agents; D008054:Lipid Peroxides; C068460:hydroxyethyl starch-deferoxamine conjugate; D003676:Deferoxamine