Effect on biochemical markers of brain injury of therapy with deferoxamine or superoxide dismutase following cardiac arrest

Abstract

Iron-mediated lipid peroxidation by oxygen radical mechanisms is thought to be a contributing factor to neurological injury during reperfusion following resuscitation from cardiac arrest. This study was designed to examine and compare the effects of an iron chelator (deferoxamine) and superoxide dismutase (SOD) on brain lipid peroxidation and tissue ions after eight hours of reperfusion following a 15-minute cardiac arrest. This sampling time was chosen because other work with this model has shown severe ionic and ultrastructural derangement at this point. Twenty-three dogs were anesthetized with ketamine and halothane and divided into four groups. Six dogs were nonischemic controls (group I). In the remaining dogs, a 15-minute cardiac arrest was induced with KCl. Resuscitation was begun with internal cardiac massage and artificial ventilation. After five minutes of artificial perfusion, internal defibrillation was performed to restart the heart. All dogs were resuscitated and supported by a standard intensive care (SIC) protocol for eight hours. Six resuscitated dogs served as SIC controls (group II). Six were treated with deferoxamine, 200 mg/kg loading dose and 100 mg/kg/h maintenance drip (group III), and five were treated with SOD, 1,000,000 units bolus and 500,000 units/h drip (group IV). All drugs were administered intravenously immediately postresuscitation. At eight hours postresuscitation, a 3-g portion of parietal cerebral cortex was obtained through a trephine hole. The sample was assayed for tissue malondialdehyde (MDA) by the thiobarbituric acid test, the double bond content of the tissue lipids (lipid unsaturation index, LUSI), and total tissue content of K and Na. Deferoxamine treatment inhibited peroxidation of brain lipids by both the MDA and LUSI assays, and protected tissue K Na ratio. SOD treatment inhibited only MDA. Iron chelation therapy appears to be promising for the membrane component of reperfusion injury.