THE MONOSIALOGANGLIOSIDE, GM(1), REDUCES NEUROLOGIC INJURY ASSOCIATEDWITH HYPOTHERMIC CIRCULATORY ARREST

Background. Neurologic injury associated with prolonged hypothermic ci rculatory arrest (HCA) may be mediated by calcium-dependent glutamate excitotoxicity (GE). The monosialoganglioside GM1 has been shown in vi tro to limit GE in conditions of metabolic stress. To test the hypothe sis that gangliosides can prevent HCA-induced brain injury, GM1 was us ed in a canine model of HCA. Methods. Twelve male dogs were placed on closed-chest cardiopulmonary bypass, subjected to 2 hours of HCA at 18 -degrees-C, and rewarmed to 35-degrees to 37-degrees-C on closed-chest cardiopulmonary bypass. All were mechanically ventilated and monitore d for 20 hours before extubation and survived for 3 days. Group 1 dogs (n = 6) were pretreated with GM1, 30 mg/kg/24 hr for 3 days before HC A, and received continuous infusion of GM1 during the procedure and 30 mg/kg/24 hr for 3 days after HCA. Group 2 dogs (n = 6) received vehic le only. With a species-specific behavior scale that yielded a neurode ficit score ranging from 0% (normal) to 100% (brain dead), all animals were neurologically assessed every 12 hours. After death at 72 hours, brains were examined by glutamate receptor autoradiography and by his tologic examination for patterns of selective neuronal necrosis and we re scored blindly from 0 (normal) to 100 (severe injury). Results. Gro up 1 dogs had better neurologic function compared with group 2 (neurod eficit score, 4.2% +/- 3% vs 38.4% +/- 8%; p < 0.001) and had less neu ronal injury (11.3 +/- 3 vs 48.3 +/- 9, p < 0.001). Densitometric rece ptor autoradiography revealed preservation of neuronal glutamate recep tor expression in group 1 only. Conclusions. These results provide evi dence of a role for GE in the development of HCA-induced brain injury and suggest that monosialogangliosides may have a neuroprotective capa city in prolonged periods of HCA.