Protective effects of fluoxetine on decompression sickness in mice

Jean-Eric Blatteau, Sandrine Barre, Aurelie Pascual, Olivier Castagna, Jacques H Abraini, Jean-Jacques Risso, Nicolas Vallee, Jean-Eric Blatteau, Sandrine Barre, Aurelie Pascual, Olivier Castagna, Jacques H Abraini, Jean-Jacques Risso, Nicolas Vallee

Abstract

Massive bubble formation after diving can lead to decompression sickness (DCS) that can result in central nervous system disorders or even death. Bubbles alter the vascular endothelium and activate blood cells and inflammatory pathways, leading to a systemic pathophysiological process that promotes ischemic damage. Fluoxetine, a well-known antidepressant, is recognized as having anti-inflammatory properties at the systemic level, as well as in the setting of cerebral ischemia. We report a beneficial clinical effect associated with fluoxetine in experimental DCS. 91 mice were subjected to a simulated dive at 90 msw for 45 min before rapid decompression. The experimental group received 50 mg/kg of fluoxetine 18 hours before hyperbaric exposure (n = 46) while controls were not treated (n = 45). Clinical assessment took place over a period of 30 min after surfacing. At the end, blood samples were collected for blood cells counts and cytokine IL-6 detection. There were significantly fewer manifestations of DCS in the fluoxetine group than in the controls (43.5% versus 75.5%, respectively; p = 0.004). Survivors showed a better and significant neurological recovery with fluoxetine. Platelets and red cells were significantly decreased after decompression in controls but not in the treated mice. Fluoxetine reduced circulating IL-6, a relevant marker of systemic inflammation in DCS. We concluded that fluoxetine decreased the incidence of DCS and improved motor recovery, by limiting inflammation processes.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1. Flow chart describing the experimental…
Figure 1. Flow chart describing the experimental design.
Figure 2. Percents of symptomatic mice suffering…
Figure 2. Percents of symptomatic mice suffering from decompression sickness (DCS) within 30 min after surfacing.
Histogram in dark grey represents the mice treated with fluoxetine and light grey represents the controls. *denotes p

Figure 3. Percents of successful grip tests…

Figure 3. Percents of successful grip tests (suspension time ≥30 sec) in dark grey for…

Figure 3. Percents of successful grip tests (suspension time ≥30 sec) in dark grey for the mice treated with fluoxetine and light grey for the controls.
Grip tests were performed in each group to quantify forelimb involvement 15 and 30 min after surfacing. $ denotes p

Figure 4. Percents of blood cells consumption…

Figure 4. Percents of blood cells consumption after decompression from the baseline in dark grey…

Figure 4. Percents of blood cells consumption after decompression from the baseline in dark grey for the mice treated with fluoxetine and light grey for the controls.
*denotes a significant difference between pre- and post-decompression. On the right, changes (%) in circulating cytokine IL-6 levels after decompression from the baseline. $ denotes a significant difference between groups. *denotes p
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References
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    1. Francis T, Mitchell S (2003) Pathophysiology of decompression sickness. Brubbak A, Neuman T (eds): The Bennett and Elliot’s physiology and medicine of diving (5th Ed). London: WB Saunders. pp 530–556.
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Figure 3. Percents of successful grip tests…
Figure 3. Percents of successful grip tests (suspension time ≥30 sec) in dark grey for the mice treated with fluoxetine and light grey for the controls.
Grip tests were performed in each group to quantify forelimb involvement 15 and 30 min after surfacing. $ denotes p

Figure 4. Percents of blood cells consumption…

Figure 4. Percents of blood cells consumption after decompression from the baseline in dark grey…

Figure 4. Percents of blood cells consumption after decompression from the baseline in dark grey for the mice treated with fluoxetine and light grey for the controls.
*denotes a significant difference between pre- and post-decompression. On the right, changes (%) in circulating cytokine IL-6 levels after decompression from the baseline. $ denotes a significant difference between groups. *denotes p
Similar articles
References
    1. Bert P (1978) Barometric pressure (La Pression Barométrique, 1878). Bethesda, MD: Undersea Medical Society; translated by Hitchcok, MA and Hitchcok, FA in 1978. 1183 p.
    1. Francis T, Mitchell S (2003) Pathophysiology of decompression sickness. Brubbak A, Neuman T (eds): The Bennett and Elliot’s physiology and medicine of diving (5th Ed). London: WB Saunders. pp 530–556.
    1. Blatteau JE, Gempp E, Simon O, Coulange M, Delafosse B, et al. (2011) Prognostic factors of spinal cord decompression sickness in recreational diving: retrospective and multicentric analysis of 279 cases. Neurocrit Care 15: 120–127. - PubMed
    1. Ersson A, Linder C, Ohlsson K, Ekholm A (1998) Cytokine response after acute hyperbaric exposure in the rat. Undersea Hyperb Med 25: 217–221. - PubMed
    1. Broussolle B, Méliet JL (2006) Broussolle B (2e Ed) Physiologie et médecine de la plongée. Paris: Ellipses, Editions Marketing. 880 p.
Show all 44 references
MeSH terms
Grant support
There are no current external funding sources for this study.
[x]
Cite
Copy Download .nbib
Format: AMA APA MLA NLM
Figure 4. Percents of blood cells consumption…
Figure 4. Percents of blood cells consumption after decompression from the baseline in dark grey for the mice treated with fluoxetine and light grey for the controls.
*denotes a significant difference between pre- and post-decompression. On the right, changes (%) in circulating cytokine IL-6 levels after decompression from the baseline. $ denotes a significant difference between groups. *denotes p

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