Deferoxamine improves early postresuscitation reperfusion after prolonged cardiac arrest in rats.
The no-reflow phenomenon and delayed hypoperfusion after transient cardiac arrest (CA) impede postischemic recovery. Activation of lipid peroxidation (LPO) after ischemia and reperfusion is considered one of the mechanisms responsible for such abnormalities. The present study investigates the influence of iron-dependent LPO inhibitor deferoxamine (DFO) on the cerebral perfusion after prolonged CA and resuscitation. Fourteen male Sprague-Dawley rats were subjected to 17 minutes of CA, induced by esmolol (an ultrashort-acting beta-blocker) and apnea, followed by resuscitation by retrograde intraaortic infusion of oxygenated donor blood mixed with a resuscitation cocktail inside a vertical-bore 9.4-T magnetic resonance imaging (MRI) magnet. Animals were randomized double-blindly into two groups to receive DFO or saline, respectively. Cerebral perfusion was measured by MRI continuously using the arterial spin-labeling method before, during, and after CA. All animals were successfully resuscitated in 1.36 +/- 0.04 minutes with well-controlled arrest time (17.99 +/- 0.03 minutes) in both groups. Deferoxamine significantly increased cerebral perfusion in hippocampus, thalamus, hypothalamus, and amygdala, but not in cortex, during the first 20 minutes of reperfusion. In the DFO-treated group, the neurologic deficit score was significantly better (400 +/- 30 vs. 250 +/- 47, out of 500 as the best, P < 0.05) and weight loss was significantly less (33 +/- 6 vs. 71 +/- 19 g, P < 0.05) 5 d after arrest. The finding supports the notion that early reperfusion immediately after resuscitation is important for long-term outcome and that LPO may be involved in microvascular disorders during the reperfusion, particularly in the brain after prolonged cardiac arrest and resuscitation.
Liachenko
Serguei
S
Department of Anesthesiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, U.S.A.
Tang
Pei
P
Xu
Yan
Y
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002560:Cerebrovascular Circulation; D003676:Deferoxamine / Q000494:pharmacology*; D006323:Heart Arrest; D006339:Heart Rate / Q000187:drug effects; D007502:Iron Chelating Agents / Q000494:pharmacology*; D015227:Lipid Peroxidation; D008279:Magnetic Resonance Imaging; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
D007502:Iron Chelating Agents; D003676:Deferoxamine