title: Mechanism of action of antiplatelet drugs on decompression sickness in rats: a protective effect of anti-GPIIbIIIa therapy.
abstract: Literature highlights the involvement of disseminated thrombosis in the pathophysiology of decompression sickness (DCS). We examined the effect of several antithrombotic treatments targeting various pathways on DCS outcome: acetyl salicylate, prasugrel, abciximab, and enoxaparin. Rats were randomly assigned to six groups. Groups 1 and 2 were a control nondiving group (C; n = 10) and a control diving group (CD; n = 30). Animals in Groups 3 to 6 were treated before hyperbaric exposure (HBE) with either prasugrel (n = 10), acetyl salicylate (n = 10), enoxaparin (n = 10), or abciximab (n = 10). Blood samples were taken for platelet factor 4 (PF4), thiobarbituric acid reactive substances (TBARS), and von Willebrand factor analysis. Onset of DCS symptoms and death were recorded during a 60-min observation period after HBE. Although we observed fewer outcomes of DCS in all treated groups compared with the CD, statistical significance was reached in abciximab only (20% vs. 73%, respectively, P = 0.007). We also observed significantly higher levels of plasmatic PF4 in abciximab (8.14 ± 1.40 ng/ml; P = 0.004) and enoxaparin groups (8.01 ± 0.80 ng/ml; P = 0.021) compared with the C group (6.45 ± 1.90 ng/ml) but not CD group (8.14 ± 1.40 ng/ml). Plasmatic levels of TBARS were significantly higher in the CD group than the C group (49.04 ± 11.20 μM vs. 34.44 ± 5.70 μM, P = 0.002). This effect was prevented by all treatments. Our results suggest that abciximab pretreatment, a powerful glycoprotein IIb/IIIa receptor antagonist, has a strong protective effect on decompression risk by significantly improving DCS outcome. Besides its powerful inhibitory action on platelet aggregation, we suggest that abciximab could also act through its effects on vascular function, oxidative stress, and/or inflammation.
authors: Orphy Laboratory, Université de Bretagne Occidentale, Brest, France; Université de Toulon, LAMHESS, La Garde, France; and Université Nice Sophia Antipolis, LAMHESS, Nice, France lambrechtskate@hotmail.com.
authors: Kate
authors: K
authors: Lambrechts
authors: Diving and Hyperbaric Department, French Navy Diving School, Toulon, France;
authors: Jean-Michel
authors: JM
authors: Pontier
authors: Orphy Laboratory, Université de Bretagne Occidentale, Brest, France;
authors: Aleksandra
authors: A
authors: Mazur
authors: Orphy Laboratory, Université de Bretagne Occidentale, Brest, France;
authors: Michaël
authors: M
authors: Theron
authors: Orphy Laboratory, Université de Bretagne Occidentale, Brest, France;
authors: Peter
authors: P
authors: Buzzacott
authors: Orphy Laboratory, Université de Bretagne Occidentale, Brest, France;
authors: Qiong
authors: Q
authors: Wang
authors: Orphy Laboratory, Université de Bretagne Occidentale, Brest, France;
authors: Marc
authors: M
authors: Belhomme
authors: Orphy Laboratory, Université de Bretagne Occidentale, Brest, France;
authors: François
authors: http://orcid.org/0000-0002-0283-3503
authors: F
authors: Guerrero
mesh_terms: D000077284:Abciximab; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D003665:Decompression Sickness / Q000188:drug therapy* / Q000503:physiopathology*; D006931:Hyperbaric Oxygenation; D007140:Immunoglobulin Fab Fragments / Q000627:therapeutic use; D008297:Male; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D010978:Platelet Factor 4 / Q000032:analysis; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014841:von Willebrand Factor / Q000032:analysis
chemical_list: D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D017392:Thiobarbituric Acid Reactive Substances; D014841:von Willebrand Factor; D010978:Platelet Factor 4; D000077284:Abciximab
keywords: abciximab; decompression illness; platelet activation