title: Vigabatrin prevents seizure in swine subjected to hyperbaric hyperoxia.
abstract: Oxygen is the most widely used therapeutic strategy to prevent and treat decompression sickness (DCS). Oxygen prebreathe (OPB) eliminated DCS in 20-kg swine after rapid decompression from saturation at 60 feet of seawater (fsw). However, hyperbaric oxygen (HBO) has risks. As oxygen partial pressure increases, so do its toxic effects. Central nervous system (CNS) oxygen toxicity is the most severe side effect, manifesting as seizure. An adjunctive therapeutic is needed to extend OPB strategies to deeper depths and prevent/delay seizure onset. The Food and Drug Administration-approved anti-epileptic vigabatrin has prevented HBO-induced seizures in rats up to 132 fsw. This study aimed to confirm the rat findings in a higher animal model and determine whether acute high-dose vigabatrin evokes retinotoxicity symptoms seen with chronic use clinically in humans. Vigabatrin dose escalation studies were conducted 20-kg swine exposed to HBO at 132 or 165 fsw. The saline group had seizure latencies of 7 and 11 min at 165 and 132 fsw, respectively. Vigabatrin at 180 mg/kg significantly increased latency (13 and 27 min at 165 and 132 fsw, respectively); 250 mg/kg abolished seizure activity at all depths. Functional electroretinogram and histology of the retinas showed no signs of retinal toxicity in any of the vigabatrin=treated animals. In the 250 mg/kg group there was no evidence of CNS oxygen toxicity; however, pulmonary oxygen toxicity limited HBO exposure. Together, the findings from this study show that vigabatrin therapy is efficacious at preventing CNS oxygen toxicity in swine, and a single dose is not acutely associated with retinotoxicity.
authors.affiliation: Undersea Medicine Department, Naval Medical Research Center, Silver Spring, Maryland.
authors.forename: Aaron A
authors.initials: AA
authors.lastname: Hall
authors.forename: Colin
authors.initials: C
authors.lastname: Young
authors.forename: Michael
authors.initials: M
authors.lastname: Bodo
authors.forename: Richard T
authors.initials: RT
authors.lastname: Mahon
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000009:adverse effects / Q000494:pharmacology*; D003664:Decompression / Q000379:methods; D003665:Decompression Sickness / Q000517:prevention & control; D004195:Disease Models, Animal; D004242:Diving / Q000009:adverse effects; D006339:Heart Rate / Q000187:drug effects; D006931:Hyperbaric Oxygenation / Q000009:adverse effects*; D018496:Hyperoxia / Q000150:complications / Q000188:drug therapy*; D008297:Male; D051381:Rats; D012160:Retina / Q000187:drug effects / Q000502:physiology; D012640:Seizures / Q000209:etiology / Q000517:prevention & control*; D034421:Sus scrofa; D020888:Vigabatrin / Q000009:adverse effects / Q000494:pharmacology*
chemical_list: D000927:Anticonvulsants; D020888:Vigabatrin
keywords: decompression illness; oxygen prebreathe; oxygen toxicity; saturation diving