Abstract

Objective: Profound hypothermia has been the only major strategy employed for protection of the brain during circulatory arrest on arch replacement. Currently, it has been reported that excitatory amino acid induces cerebral neuron injury after brain ischemia, and NMDA and AMPA/KA receptor antagonists have the potential to protect the brain during cerebral ischemia. We investigated whether a novel AMPA receptor antagonist, YM90K [6-(1H-imidazol-1-yl)-7-nitro-2,3(1H,4H)-quinoxalinedione hydrochloride], has the potential for cerebral protection with moderately hypothermic circulatory arrest.

Methods: Hypothermia was induced in sixteen piglets, 4 weeks old, weighing 9.8--11.0 kg at the tympanic temperature of 20°C (n = 3), 25°C (n = 3), 30°C (n = 10) on extracorporeal circulation and circulatory arrest was maintained for 1 hour. Rewarming was performed after 2-hour reperfusion. YM90K was given continuously into the perfusate at 10 mg/kg/h for 1 hour on 5 piglets in 30°C circulatory arrest group. Changes in high-energy phosphates and intracellular pH were observed by ³¹P magnetic resonance spectroscopy every 10 min using a two-turn surface coil of 4 cm diameter.

Results: Creatine phosphate (PCr) recovered well after 2-hour reperfusion in both 20°C (111 ± 7%) and 25°C (116 ± 26%) arrest groups. Recovery of PCr was poor in 30°C arrest group (52 ± 22%). However, in YM90K-treated 30°C arrest group PCr recovered (87 ± 19%) significantly better than the untreated group. Intracellular pH remained acidic in 30°C, YM90K untreated group, while it recovered well in other groups. Recovery of ATP was not significantly different among all groups.

Conclusion: It was confirmed that administration of YM90K improved energy metabolism and intracellular pH in cerebral tissue during moderately hypothermic circulatory arrest. YM90K has potential to protect the brain during hypothermic circulatory arrest without inducing profound hypothermia.