Lamotrigine attenuates cortical glutamate release during global cerebral ischemia in pigs on cardiopulmonary bypass

Background The dose-response effects of pretreatment with lamotrigine (a ph enyltriazine derivative that inhibits neuronal glutamate release) in a porc ine cerebral ischemia model during cardiopulmonary bypass were studied., Methods: Sagittal sinus catheters and cortical microdialysis catheters were inserted into anesthetized pigs, Animals undergoing normothermic cardiopul monary bypass were pretreated with lamotrigine 0, 10, 25, or 50 mg/kg (n = 10 per group). Fifteen minutes of global cerebral ischemia was produced, fo llowed by 40 min of reperfusion and discontinuation of cardiopulmonary bypa ss. Cerebral oxygen metabolism was calculated using cerebral blood flow (ra dioactive microspheres) and arterial-venous oxygen content gradients. Conce ntrations of microdialysate glutamate and aspartate were quantified; electr o-encephalographic signals were recorded. After cardiopulmonary bypass, blo od and cerebrospinal fluid were sampled for S-100B protein, and a biopsy wa s performed on the cerebral cortex for metabolic profile. Results: Lamotrigine caused dose-dependent reductions in systemic vascular resistance so that additional fluid was required to maintain venous return. Concentrations of glutamate and aspartate did not change during reperfusio n after 50 mg/kg lamotrigine in contrast to fivefold and twofold increases, respectively, with lower doses. There were no intergroup differences in ce rebral metabolism, electroencephalographic scores, cortical metabolites, br ain lactate, or S-100B protein concentrations in the cerebrospinal fluid an d blood. Conclusions: Lamotrigine 50 mg/kg significantly attenuated excitatory neuro transmitter release during normothermic cerebral ischemia during cardiopulm onary bypass without improving other neurologic parameters. Lamotrigine cau sed arterial and venous dilation, which limits its clinical usefulness.