Pharmacological Interventions to Decompression Sickness in Rats: Comparison of Five Agents

Montcalm-Smith, Elizabeth; Fahlman, Andreas; Kayar, Susan R.

doi:10.3357/asem.2071.2008

Cited by 16 publications

(14 citation statements)

References 25 publications

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“…In our study, there is no difference in DCS outcome and DCS severity between ASA pretreatment and control groups. This result corroborates previous studies in a rat model of DCS subjected to the same dose of 100 mg/kg three times daily for 2 days before hyperbaric exposure (18). However, only one study in a rat model of DCS has shown a significant decrease in DCS incidence (22% in ASA group vs. 40% in control group) and DCS severity (12% incidence of death in ASA group vs. 31% in control group) with ASA pretreatment before a hyperbaric exposure in a dry chamber and a fast decompression.…”

Section: Discussionsupporting

confidence: 94%

Pharmacological intervention against bubble-induced platelet aggregation in a rat model of decompression sickness

Pontier

Vallée

Ignatescu

et al. 2011

Journal of Applied Physiology

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Decompression sickness (DCS) with alterations in coagulation system and formation of platelet thrombi occurs when a subject is subjected to a reduction in environmental pressure. Blood platelet consumption after decompression is clearly linked to bubble formation in humans and offers an index for evaluating DCS severity in animal models. Previous studies highlighted a predominant involvement of platelet activation and thrombin generation in bubble-induced platelet aggregation (BIPA). To study the mechanism of the BIPA in DCS, we examined the effect of acetylsalicylic acid (ASA), heparin (Hep), and clopidogrel (Clo), with anti-thrombotic dose pretreatment in a rat model of DCS. Male Sprague-Dawley rats (n = 208) were randomly assigned to one experimental group treated before the hyperbaric exposure and decompression protocol either with ASA (3×100 mg·kg(-1)·day(-1), n = 30), Clo (50 mg·kg(-1)·day(-1), n = 60), Hep (500 IU/kg, n = 30), or to untreated group (n = 49). Rats were first compressed to 1,000 kPa (90 msw) for 45 min and then decompressed to surface in 38 min. In a control experiment, rats were treated with ASA (n = 13), Clo (n = 13), or Hep (n = 13) and maintained at atmospheric pressure for an equivalent period of time. Onset of DCS symptoms and death were recorded during a 60-min observation period after surfacing. DCS evaluation included pulmonary and neurological signs. Blood samples for platelet count (PC) were taken 30 min before hyperbaric exposure and 30 min after surfacing. Clo reduces the DCS mortality risk (mortality rate: 3/60 with Clo, 15/30 with ASA, 21/30 with Hep, and 35/49 in the untreated group) and DCS severity (neurological DCS incidence: 9/60 with Clo, 6/30 with ASA, 5/30 with Hep, and 12/49 in the untreated group). Clo reduced fall in platelet count and BIPA (-4,5% with Clo, -19.5% with ASA, -19,9% with Hep, and -29,6% in the untreated group). ASA, which inhibits the thromboxane A2 pathway, and Hep, which inhibits thrombin generation, have no protective effect on DCS incidence. Clo, a specific ADP-receptor antagonist, reduces post-decompression platelet consumption. These results point to the predominant involvement of the ADP release in BIPA but cannot differentiate definitively between bubble-induced vessel wall injury and bubble-blood component interactions in DCS.

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Section: Discussionsupporting

confidence: 94%

Pharmacological intervention against bubble-induced platelet aggregation in a rat model of decompression sickness

Pontier

Vallée

Ignatescu

et al. 2011

Journal of Applied Physiology

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“…The experimental design is detailed in Figure 1. Previous studies showed that bubble formation and incidence of decompression sickness were highly dependent upon body weight of the rat [24], [25], [26]. Protocols using rats with a body weight above 350 g produced severe DCS with severe neurological symptoms and death.…”

Section: Methodsmentioning

confidence: 99%

Sidenafil Pre-Treatment Promotes Decompression Sickness in Rats

Blatteau¹,

Brubakk

Gempp

et al. 2013

PLoS ONE

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Vascular bubble formation after decompression contributes to endothelial injuries which form the basis for the development of decompression sickness (DCS). Nitric oxide (NO) is a powerful vasodilator that contributes to vessel homeostasis. It has been shown that NO-releasing agent may reduce bubble formation and prevent serious decompression sickness. The use of sildenafil, a well-known, phosphodiesterase-5 blocker, which act by potentiating the vasodilatory effect on smooth muscle relaxation, has never been studied in DCS. The purpose of the present study was to evaluate the clinical effects of sildenafil pre-treatment on DCS in a rat model. 67 rats were subjected to a simulated dive at 90 msw for 45 min before staged decompression. The experimental group received 10 mg/kg of sildenafil one hour before exposure (n = 35) while controls were not treated (n = 32). Clinical assessment took place over a period of 30 min after surfacing. At the end, blood samples were collected for blood cells counts and the level of circulating bubbles in the right cavities was quantified. There were significantly more manifestations of DCS in the sildenafil group than in the controls (34.3% vs 6.25%, respectively, p = 0.012). Platelet count was more reduced in treated rats than in controls (−21.7% vs −7%, respectively, p = 0.029), whereas bubble grades did not differ between groups. We concluded that pre-treatment with sildenafil promotes the onset and severity of neurological DCS. When considering the use of phosphodiesterase-5 blockers in the context of diving, careful discussion with physician should be recommended.

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“…Bubble formation in blood induces activate the vascular endothelium, stimulate prothrombotic phenomena and induce inflammation: platelet and leukocyte activation have been observed, associated with elevated production of cytokines and cell adhesion stimulators [2], [4], [5]. It is now accepted that severe DCS is a systemic pathophysiological process that may induce tissue reaction that promotes ischemic damage in the spinal cord or the brain [6], [7], [8].…”

Section: Introductionmentioning

confidence: 99%

“…Indeed, increased levels of proinflammatory circulating cytokines especially IL-6, TNF alpha and IFN gamma have been detected in animal models of DCS, correlated with the upregulated expression of selectins in the lungs and brain [4], [23]. It has been suggested that the activation of the body’s defense system initiates a vicious cycle that leads to multiple organ failure unless the DCS is adequately treated [8].…”

Section: Introductionmentioning

confidence: 99%

Protective Effects of Fluoxetine on Decompression Sickness in Mice

Blatteau¹,

Barre²,

Pascual³

et al. 2012

PLoS ONE

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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.

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Pharmacological Interventions to Decompression Sickness in Rats: Comparison of Five Agents

Abstract: MONTCALM-SMITH

Cited by 16 publications

References 25 publications

Pharmacological intervention against bubble-induced platelet aggregation in a rat model of decompression sickness

Pharmacological intervention against bubble-induced platelet aggregation in a rat model of decompression sickness

Sidenafil Pre-Treatment Promotes Decompression Sickness in Rats

Protective Effects of Fluoxetine on Decompression Sickness in Mice

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