Xenon reduces neurohistopathological damage and improves the early neurological deficit after cardiac arrest in pigs.

Objective: Treatment options to ameliorate brain damage following cardiopulmonary resuscitation from cardiac arrest are limited.

Design: In a porcine model, we evaluated the effects of xenon treatment on neuropathologic and functional outcomes after cardiopulmonary resuscitation.

Setting: Prospective, randomized laboratory animal study.

Subjects: Male pigs.

Interventions: Following successful resuscitation from 8 mins of cardiac arrest and 5 mins of cardiopulmonary resuscitation, 24 pigs were randomized to one of three groups receiving either 70% xenon for 1 or 5 hrs or untreated controls receiving 70% nitrogen.

Measurements And Main Results: Gas exchange, hemodynamics, and lactate and glucose levels were measured at baseline and in the postresuscitation period. On four postoperative days, neurocognitive and overall neurologic deficits were assessed before day 5, when the brains were harvested for histologic analysis of predefined regions using a semiquantitative score (0-10% = 1, 10-20% = 2, 20-50% = 3, 50-80% = 4, 80-100% = 5). No differences in gas exchange, hemodynamics, or lactate and glucose levels were observed among the groups. Animals exposed to 1 and 5 hrs of xenon showed significantly reduced scores for necrotic neurons in the putamen (1.25 +/- 0.5 and 1.25 +/- 0.5 vs. 2.5 +/- 1.2; p < 0.05), accompanied by significantly lesser scores for perivascular inflammation in putamen (0.8 +/- 0.5 and 1.1 +/- 0.8 vs. 2.1 +/- 1.1; p < 0.05) and caudate nucleus (1.0 +/- 0.8 and 0.6 +/- 0.7 vs. 2.0 +/- 1.1; p < 0.05). This resulted in improved neurocognitive and neurologic function on day 1 to 3 after cardiopulmonary resuscitation in xenon-treated animals.

Conclusions: In this experimental study of cardiac arrest-induced neurologic damage, xenon conferred neurohistopathologic protection, translating in transiently improved functional outcome.