Protective effects of combined superoxide dismutase and deferoxamine on recovery of cerebral blood flow and function after cardiac arrest in dogs.
Oxygen free radicals generated during reoxygenation after cardiac arrest may impair recovery of cerebral blood flow and function. In a randomized study in vivo, we tested the following anti-free radical combination therapy administered at the beginning of cardiopulmonary resuscitation after apnea-induced cardiac arrest of 7 minutes: 1) ventilation with 100% nitrogen for 30 seconds to allow the delivery of therapy before oxygen, 2) 10 mg/kg i.a. superoxide dismutase followed by 10 mg/kg i.v. over 1 hour to scavenge the superoxide anion radical, and 3) 20 mg/kg i.v. deferoxamine over 1 hour to prevent membrane lipid peroxidation. We evaluated the effects of this combined treatment on the recovery of cardiovascular variables, cerebral blood flow and oxygen consumption, and somatosensory evoked potentials in 20 dogs 6 hours after resuscitation. Compared with standard treatment (n = 10), the combined treatment (n = 10) did not affect cardiovascular variables, significantly mitigated cerebral blood flow changes after cardiac arrest, and enhanced recovery of somatosensory evoked potentials. We conclude that oxygen free radicals play a role in the pathogenesis of the arrest-related derangements of cerebral blood flow and function that are effectively reduced by this combined treatment; we recommend evaluation of its components in outcome studies.
D000818:Animals; D001921:Brain / Q000378:metabolism; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D002561:Cerebrovascular Disorders / Q000517:prevention & control*; D003676:Deferoxamine / Q000627:therapeutic use*; D004285:Dogs; D005073:Evoked Potentials, Somatosensory; D005609:Free Radicals; D006323:Heart Arrest / Q000150:complications*; D008297:Male; D009584:Nitrogen / Q000627:therapeutic use; D010101:Oxygen Consumption; D012151:Resuscitation; D013482:Superoxide Dismutase / Q000627:therapeutic use*
D005609:Free Radicals; D013482:Superoxide Dismutase; D003676:Deferoxamine; D009584:Nitrogen