Treatment with the competitive NMDA antagonist GPI 3000 does not improve outcome after cardiac arrest in dogs
Abstract
We previously showed that treatment with a competitive N-methyl-D-aspartate (NMDA) receptor antagonist GPI-3000 (GPI) improved short-term physiological recovery after incomplete global cerebral ischemia complicated by dense acidosis. We tested the hypothesis that GPI administered after resuscitation from cardiac arrest would improve a more long-term recovery as measured by neurobehavioral assessment and neuropathology 4 days after resuscitation. Anesthetized dogs were subjected to 7 minutes of cardiac arrest followed by vest cardiopulmonary resuscitation. Neurobehavioral outcomes were scored daily on a score ranging from 0 (normal) to 500 (worst). On the fourth day, the animals were killed, and neuropathology was evaluated in a blinded manner in the hippocampus and the neocortex by hematoxylin and eosin staining and by determination of percentage of injured neurons. Three groups of animals were treated in a randomized, blinded protocol with either saline (SAL), low-dose GPI (5 mg/kg followed by 1 mg/kg per hour for 2 hours), or high-dose GPI (25 mg/kg, followed by 5 mg/kg per hour for 2 hours). The mortality rate was higher in animals receiving GPI than in saline-treated control animals (4 of 15 deaths in SAL, 6 of 15 in the lo...Continue Reading
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