Oxygenation strategy and neurologic damage after deep hypothermic circulatory arrest. II. Hypoxic versus free radical injury

Objectives: Laboratory studies suggest that myocardial reperfusion injury i s exacerbated by free radicals when pure oxygen is used during cardiopulmon ary bypass. In phase I of this study we demonstrated that normoxic perfusio n during cardiopulmonary bypass does not increase the risk of microembolic brain injury so long as a membrane oxygenator with an arterial filter is us ed, In phase II of this study we studied the hypothesis that normoxic perfu sion increases the risk of hypoxic brain injury after deep hypothermia with circulatory arrest. Methods: With membrane oxygenators with arterial biter s, 10 piglets (8-10 kg) underwent 120 minutes of deep hypothermia and circu latory arrest at 15 degrees C, were rewarmed to 37 degrees C, and were wean ed from bypass, In 5 piglets normoxia (Pao(2) 64-181 mm Hg) was used during cardiopulmonary bypass and in 5 hyperoxia (Pao(2) 400-900 mm Hg) was used, After 6 hours of reperfusion the brain was fixed for histologic evaluation . Near-infrared spectroscopy was used to monitor cerebral oxyhemoglobin and oxidized cytochrome a,a(3) concentrations, Results: Histologic examination revealed a significant increase in brain damage in the normoxia group (sco re 12.4 versus 8.6, P = .01), especially in the neocortex and hippocampal r egions. Cytochrome a,a(3) and oxyhemoglobin concentrations tended to be low er during deep hypothermia and circulatory arrest in the normoxia group (P = .16), Conclusions: In the setting of prolonged deep hypothermia and circu latory arrest with membrane oxygenators, normoxic cardiopulmonary bypass si gnificantly increases histologically graded brain damage with respect to hy peroxic cardiopulmonary bypass. Near-infrared spectroscopy suggests that th e mechanism is hypoxic injury, which presumably overwhelms any injury cause d by increased oxygen free radicals.