Ulinastatin: A Potential Alternative to Glucocorticoid in the Treatment of Severe Decompression Sickness

Inflammatory reaction is the crux in various clinical critical diseases including decompression sickness (DCS). Ulinastatin (UTI), a potent anti-inflammatory agent, has been used clinically, including as a substitution for steroids. This study aimed to explore the potential effects of UTI upon DCS i...

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Main Authors: Wen-tao Meng, Long Qing, Chun-zhen Li, Kun Zhang, Hong-jie Yi, Xu-peng Zhao, Wei-gang Xu
Format: Article
Language:English
Published: Frontiers Media S.A. 2020-03-01
Series:Frontiers in Physiology
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fphys.2020.00273/full
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author Wen-tao Meng
Long Qing
Chun-zhen Li
Kun Zhang
Hong-jie Yi
Xu-peng Zhao
Wei-gang Xu
author_facet Wen-tao Meng
Long Qing
Chun-zhen Li
Kun Zhang
Hong-jie Yi
Xu-peng Zhao
Wei-gang Xu
author_sort Wen-tao Meng
collection DOAJ
description Inflammatory reaction is the crux in various clinical critical diseases including decompression sickness (DCS). Ulinastatin (UTI), a potent anti-inflammatory agent, has been used clinically, including as a substitution for steroids. This study aimed to explore the potential effects of UTI upon DCS in a rabbit model. Eighty-eight rabbits were subjected to simulated diving to 6 atmospheres absolute (ATA) for 60 min with 2.5-minute decompression. Three doses of UTI (15/7.5/3.75 × 105 U/kg) or saline were intravenously administered immediately following decompression. Circulating bubbles were monitored for 3 h following decompression and DCS signs were evaluated for 24 h. Blood was sampled 8 times during 72 h after decompression for inflammatory, endothelial, oxidative and routine blood indices. Lung tissues were also sampled for evaluating endothelial function. Another six rabbits were used as Normal controls. In the high dose UTI group the mortality, general morbidity and incidence of severe DCS was decreased from 31.25 to 9.38% (P = 0.030), 84.38 to 62.50% (P = 0.048) and 46.88 to 21.88% (P = 0.035), respectively. The high dose of UTI significantly postponed the occurrence of DCS (P = 0.030) and prolonged survival time (P = 0.009) compared with the Saline group, and significantly ameliorated inflammation responses, endothelial injuries and oxidative damage. The results strongly suggest the benefit of UTI on DCS, especially for severe cases. Large doses are needed to achieve significant effects. UTI may be a potential ideal pharmacological candidate for the treatment of severe DCS.
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spelling doaj.art-5a1d490dc724418d8dbad494276aed602022-12-21T18:40:50ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2020-03-011110.3389/fphys.2020.00273531829Ulinastatin: A Potential Alternative to Glucocorticoid in the Treatment of Severe Decompression SicknessWen-tao Meng0Long Qing1Chun-zhen Li2Kun Zhang3Hong-jie Yi4Xu-peng Zhao5Wei-gang Xu6Department of Diving and Hyperbaric Medicine, Naval Special Medicine Center, Naval Medical University, Shanghai, ChinaNaval Diving Medical Discipline, Naval Special Medicine Center, Naval Medical University, Shanghai, ChinaSchool of Basic Medicines, Naval Medical University, Shanghai, ChinaDepartment of Diving and Hyperbaric Medicine, Naval Special Medicine Center, Naval Medical University, Shanghai, ChinaDepartment of Diving and Hyperbaric Medicine, Naval Special Medicine Center, Naval Medical University, Shanghai, ChinaDepartment of Diving and Hyperbaric Medicine, Naval Special Medicine Center, Naval Medical University, Shanghai, ChinaDepartment of Diving and Hyperbaric Medicine, Naval Special Medicine Center, Naval Medical University, Shanghai, ChinaInflammatory reaction is the crux in various clinical critical diseases including decompression sickness (DCS). Ulinastatin (UTI), a potent anti-inflammatory agent, has been used clinically, including as a substitution for steroids. This study aimed to explore the potential effects of UTI upon DCS in a rabbit model. Eighty-eight rabbits were subjected to simulated diving to 6 atmospheres absolute (ATA) for 60 min with 2.5-minute decompression. Three doses of UTI (15/7.5/3.75 × 105 U/kg) or saline were intravenously administered immediately following decompression. Circulating bubbles were monitored for 3 h following decompression and DCS signs were evaluated for 24 h. Blood was sampled 8 times during 72 h after decompression for inflammatory, endothelial, oxidative and routine blood indices. Lung tissues were also sampled for evaluating endothelial function. Another six rabbits were used as Normal controls. In the high dose UTI group the mortality, general morbidity and incidence of severe DCS was decreased from 31.25 to 9.38% (P = 0.030), 84.38 to 62.50% (P = 0.048) and 46.88 to 21.88% (P = 0.035), respectively. The high dose of UTI significantly postponed the occurrence of DCS (P = 0.030) and prolonged survival time (P = 0.009) compared with the Saline group, and significantly ameliorated inflammation responses, endothelial injuries and oxidative damage. The results strongly suggest the benefit of UTI on DCS, especially for severe cases. Large doses are needed to achieve significant effects. UTI may be a potential ideal pharmacological candidate for the treatment of severe DCS.https://www.frontiersin.org/article/10.3389/fphys.2020.00273/fullulinastatindecompression sicknessinflammationendothelial injuryrabbit
spellingShingle Wen-tao Meng
Long Qing
Chun-zhen Li
Kun Zhang
Hong-jie Yi
Xu-peng Zhao
Wei-gang Xu
Ulinastatin: A Potential Alternative to Glucocorticoid in the Treatment of Severe Decompression Sickness
Frontiers in Physiology
ulinastatin
decompression sickness
inflammation
endothelial injury
rabbit
title Ulinastatin: A Potential Alternative to Glucocorticoid in the Treatment of Severe Decompression Sickness
title_full Ulinastatin: A Potential Alternative to Glucocorticoid in the Treatment of Severe Decompression Sickness
title_fullStr Ulinastatin: A Potential Alternative to Glucocorticoid in the Treatment of Severe Decompression Sickness
title_full_unstemmed Ulinastatin: A Potential Alternative to Glucocorticoid in the Treatment of Severe Decompression Sickness
title_short Ulinastatin: A Potential Alternative to Glucocorticoid in the Treatment of Severe Decompression Sickness
title_sort ulinastatin a potential alternative to glucocorticoid in the treatment of severe decompression sickness
topic ulinastatin
decompression sickness
inflammation
endothelial injury
rabbit
url https://www.frontiersin.org/article/10.3389/fphys.2020.00273/full
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