AMPA ANTAGONIST LY293558 DOES NOT AFFECT THE SEVERITY OF HYPOXIC-ISCHEMIC INJURY IN NEWBORN PIGS

Background and Purpose LY293558 is a systemically active lpha-amino-3- hydroxy-5-methyl-4-isosazolepropionic acid (AMPA) excitatory amino aci d antagonist. AMPA antagonists have shown promise in several adult hyp oxic-ischemic brain injury models, and we wanted to see if this work c ould be extended to a newborn animal. Methods Seventy-six (beta error < .10) 0- to 3-day-old piglets under 1.5% isoflurane anesthesia underw ent placement of carotid snares and arterial and venous catheters. Whi le paralyzed with succinylcholine under 0.5% isoflurane, 50% nitrous o xide, piglets were randomly assigned to receive either 5 mg/kg or 15 m g/kg of LY293558 or saline at time -10 minutes and again 10 hours late r. At time 0, both carotid arteries were clamped, and blood was withdr awn to reduce the blood pressure to two thirds of normal. At time 15 m inutes, inspired oxygen was reduced to 6%. At time 30 minutes, the car otid snares were released, the withdrawn blood was reinfused, and the oxygen was switched to 100%. On the third day after the hypoxic-ischem ic injury, the animals were killed by perfusion of the brain with 10% formalin. Brain pathology was scored by a blinded observer. Results Th ere were no significant differences between the drug-treated and contr ol groups. Conclusions The systemically active AMPA antagonist LY29355 8, when given at a dose of 5 mg/kg or 15 mg/kg before injury and 10 ho urs later, does not affect the severity of hypoxic-ischemic brain inju ry in newborn piglets. Neither AMPA receptor activity nor NMDA recepto r activity are important in brain injury in this model.