INTRODUCTION: Perfluorocarbon (PFC) formulations can be a useful adjunct treatment for decompression sickness (DCS) when staged decompression procedures cannot be followed due to time constraints or lack of equipment. The benefit of PFC treatment is believed to result from its ability to transport more dissolved gas than can be transported by blood alone. Dodecylfluoropentane (DDFPe) is a unique nanodroplet compound that expands into a gaseous state when exposed to physiological temperatures, resulting in a higher dissolved gas-carrying capacity than standard PFC formulations.METHODS: We investigated the efficacy of DDFPe in reducing morbidity and mortality in a rat model of severe DCS. Male Sprague-Dawley rats (250-280 g) were compressed to 210 fsw for 60 min before rapid decompression. Animals were immediately injected with 2% DDFPe (0.07 ml · kg⁻¹, 0.5 ml · kg⁻¹, 1.0 ml · kg⁻¹) or saline, and were transferred to a 100% O₂ environment for 30 min.RESULTS: Of the animals in the saline group, 47% (18/38) did not survive the decompression event, while ∼98% (46/47) of the animals in the DDFPe group did not survive. Of the animals that died during the observation period, the saline group survived on average 89% longer than DDFPe treated animals. Seizures occurred in 42% of the DDFPe group vs. 16% in the saline group. Histological analysis revealed the presence of large, multifocal gas emboli in the liver and heart of DDFPe treated animals.CONCLUSIONS: We conclude that DDFPe is not an effective nonrecompressive treatment for DCS in rodents.Sheppard RL, Regis DP, Mahon RT. Dodecafluoropentane (DDFPe) and decompression sickness-related mortality in rats. Aerosp Med Hum Perform. 2015; 86(1):21–26.