The free radical spin trap α-phenyl-tert-butyl nitrone attenuates the cerebral response to deep hypothermic ischemia

AbstractObjective: The aim of this study was to assess the role of reactive oxygen species in the impairment of cerebral recovery that follows deep hypothermic circulatory arrest. Methods: Twelve 1-week-old piglets were randomized to placebo (control group; n = 6) or 100 mg · kg–1 intravenous α-phenyl-tert -butyl nitrone, a free radical spin trap (PBN group; n = 6). All piglets underwent cardiopulmonary bypass, cooling to 18°C, 60 minutes of circulatory arrest followed by 60 minutes of reperfusion, and rewarming. Cerebral blood flow and metabolism were determined at baseline before deep hypothermic circulatory arrest and after 60 minutes of reperfusion. Results: In control animals, mean global cerebral blood flow (± 1 standard error) before circulatory arrest was 48.4 ± 3.6 mL · 100 g–1 · min–1 and fell to 25.1 ± 3.6 mL · 100 g–1 · min–1 after circulatory arrest (P = .001). Global cerebral metabolism fell from 3.5 ± 0.2 mL · 100 g–1 · min–1 before arrest to 2.2 ± 0.2 mL · 100 g–1 · min–1 after circulatory arrest (P = .0002). In the PBN group after circulatory arrest, the mean global cerebral blood flow and metabolism of 37.2 ± 4.9 and 3.6 ± 0.5 mL · 100 g–1 · min–1, respectively, were significantly higher than in the control group (P < .05). Recovery of cerebral blood flow in the PBN group was 78% of pre-arrest level compared with 52% in the control group (P = .002). Global cerebral metabolism after circulatory arrest was 100% of the pre-arrest value compared with 61% in the control group (P = .01). Regional recovery of cerebral metabolism in the cerebellum, brain stem, and basal ganglia was 131%, 130%, and 115%, respectively, of pre-arrest values in the PBN group compared with 85%, 78%, and 70% in the control group (P < .04). Conclusions: Reactive oxygen species contribute to the impairment of cerebral recovery that follows deep hypothermic circulatory arrest. The use of α-phenyl-tert -butyl nitrone before the arrest period attenuates the normal response to ischemia and improves recovery by affording protection from free radical–mediated damage. (J Thorac Cardiovasc Surg 2000;119:305-13