This study examined whether macromol. nitroxide can work as extracellular superoxide dismutase mimetic in cancer and stroke therapy.Results suggest that VACNO and SanFlow working as SOD3-mimetics may provide a paradigm change for both stroke and cancer therapies.

01 Mar 2012·Journal of Cerebral Blood Flow & MetabolismQ2 · MEDICINE

Polynitroxyl Albumin and Albumin Therapy after Pediatric Asphyxial Cardiac Arrest: Effects on Cerebral Blood Flow and Neurologic Outcome

Q2 · MEDICINE

Article

Author: Clark, Robert S B ; Garman, Robert ; Foley, Lesley M ; Ma, Li ; Ho, Chien ; Bayır, Hülya ; Hitchens, T Kevin ; Hsia, Carleton J C ; Alexander, Henry ; Kochanek, Patrick M ; Manole, Mioara D

Postresuscitation cerebral blood flow (CBF) disturbances and generation of reactive oxygen species likely contribute to impaired neurologic outcome after pediatric cardiac arrest (CA). Hence, we determined the effects of the antioxidant colloid polynitroxyl albumin (PNA) versus albumin or normal saline (NS) on CBF and neurologic outcome after asphyxial CA in immature rats. We induced asphyxia for 9 minutes in male and female postnatal day 16 to 18 rats randomized to receive PNA, albumin, or NS at resuscitation from CA or sham surgery. Regional CBF was measured serially from 5 to 150 minutes after resuscitation by arterial spin-labeled magnetic resonance imaging. We assessed motor function (beam balance and inclined plane), spatial memory retention (water maze), and hippocampal neuronal survival. Polynitroxyl albumin reduced early hyperemia seen 5 minutes after CA. In contrast, albumin markedly increased and prolonged hyperemia. In the delayed period after resuscitation (90 to 150 minutes), CBF was comparable among groups. Both PNA- and albumin-treated rats performed better in the water maze versus NS after CA. This benefit was observed only in males. Hippocampal neuron survival was similar between injury groups. Treatment of immature rats with PNA or albumin resulted in divergent acute changes in CBF, but both improved spatial memory retention in males after asphyxial CA.

01 Feb 2011·Critical Care MedicineQ1 · MEDICINE

Normoxic versus hyperoxic resuscitation in pediatric asphyxial cardiac arrest: Effects on oxidative stress

Q1 · MEDICINE

Article

Author: Bayir, Hulya ; Kochanek, Patrick M. ; Ma, Li ; Kagan, Valerian E. ; Alexander, Henry ; Glumac, Ashley ; Tang, Minke ; Hsia, Carelton J. ; Manole, Mioara D. ; Clark, Robert S. ; Walson, Karen H.

OBJECTIVETo determine the effects of normoxic vs. hyperoxic resuscitation on oxidative stress in a model of pediatric asphyxial cardiac arrest.DESIGNProspective, interventional study.SETTINGUniversity research laboratory.SUBJECTSPostnatal day 16-18 rats (n = 5 per group).INTERVENTIONSRats underwent asphyxial cardiac arrest for 9 min. Rats were randomized to receive 100% oxygen, room air, or 100% oxygen with polynitroxyl albumin (10 mL·kg⁻¹ intravenously, 0 and 30 min after resuscitation) for 1 hr from the start of cardiopulmonary resuscitation. Shams recovered in 100% oxygen or room air after surgery.MEASUREMENTS AND MAIN RESULTSPhysiological variables were recorded at baseline to 1 hr after resuscitation. At 6 hrs after asphyxial cardiac arrest, levels of reduced glutathione and protein-thiols (fluorescent assay), activities of total superoxide dismutase and mitochondrial manganese superoxide dismutase (cytochrome c reduction method), manganese superoxide dismutase expression (Western blot), and lipid peroxidation (4-hydroxynonenal Michael adducts) were evaluated in brain tissue homogenates. Hippocampal 3-nitrotyrosine levels were determined by immunohistochemistry 72 hrs after asphyxial cardiac arrest. Survival did not differ among groups. At 1 hr after resuscitation, Pao2, pH, and mean arterial pressure were decreased in room air vs. 100% oxygen rats (59 ± 3 vs. 465 ± 46 mm Hg, 7.36 ± 0.05 vs. 7.42 ± 0.03, 35 ± 4 vs. 45 ± 5 mm Hg; p < .05). Rats resuscitated with 100% oxygen had decreased hippocampal reduced glutathione levels vs. sham (15.3 ± 0.4 vs. 20.9 ± 4.1 nmol·mg protein⁻¹; p < .01). Hippocampal manganese superoxide dismutase activity was significantly increased in 100% oxygen rats vs. sham (14 ± 2.4 vs. 9.5 ± 1.6 units·mg protein⁻¹, p < .01), with no difference in protein expression of manganese superoxide dismutase. Room air and 100% oxygen plus polynitroxyl albumin groups had hippocampal reduced glutathione and manganese superoxide dismutase activity levels comparable with sham. Protein thiol levels were unchanged across groups. Compared with all other groups, rats receiving 100% oxygen had increased immunopositivity for 3-nitrotyrosine in the hippocampus and increased lipid peroxidation in the cortex.CONCLUSIONSResuscitation with 100% oxygen leads to increased oxidative stress in a model that mimics pediatric cardiac arrest. This may be prevented by using room air or giving an antioxidant with 100% oxygen resuscitation.

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