Increased intracerebral excitatory amino acids and nitric oxide after hypothermic circulatory arrest

Background. Prolonged hypothermic circulatory arrest (HCA) results in neuro logic injury, but the mechanism of this injury is unknown. This study was u ndertaken to measure quantitatively intracerebral excitatory amino acids an d citrulline, an equal coproduct of nitric oxide, during HCA. We hypothesiz ed that HCA resulted in higher levels of glutamate, aspartate, glycine, cau sing increased intracellular calcium, and therefore, nitric oxide and citru lline. Methods. Ten dogs underwent intracerebral microdialysis and 2 hours of HCA at 18 degrees C. Effluent was analyzed by high performance liquid chromatog raphy with electrochemical detection. Five dogs each were sacrificed at 8 a nd 20 hours after HCA. Neuronal apoptosis was scored fl:om 0 (no injury) to 100 (severe injury). Results. Time course of HCA was divided into six periods. Peak levels of am ino acids in each period were compared with those at baseline. Glutamate, c oagonist glycine, and citrulline, an equal coproduct of nitric oxide, incre ased significantly over baseline during HCA, cardiopulmonary bypass, and 2 to 8 hours after HCA. Aspartate increased significantly during HCA and 8 to 20 hours after HCA. Apoptosis score was 65.56 +/- 5.67 at 8 hours and 30.6 3 +/- 14.96 at 20 hours after HCA. Conclusions. Our results provide direct evidence that HCA causes increased intracerebral glutamate and aspartate, along with coagonist glycine. We con clude that HCA causes glutamate excitotoxicity with subsequent nitric oxide production resulting in neurologic injury, which begins during arrest and continues until 20 hours after hypothermic circulation arrest. To provide e ffective cerebral protection, pharmacologic strategies to reduce glutamate excitotoxicity require intervention beyond the initial ischemic insult. (C) 1999 by The Society of Thoracic Surgeons.