Mechanism of action of antiplatelet drugs on decompression sickness in rats: a protective effect of anti-GPIIbIIIa therapy

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.

Effects of Symptomatic Treatments on Cutaneous Hyperalgesia and Laser Evoked Potentials During Migraine Attack

Previously an amplitude enhancement of laser evoked potentials (LEPs) was detected during migraine attack: we further examined pain threshold to CO2 laser stimuli and LEPs during attacks, evaluating the effect of almotriptan, lysine-acetylsalicylate and placebo treatment on cutaneous hyperalgesia to thermal stimuli delivered by CO2 laser and on LEP components. Eighteen patients suffering from migraine without aura were analysed. They were divided into three groups of six patients each, randomly assigned to lysine acetyl-salicylate, almotriptan or placebo treatments. The supraorbital zones and the dorsum of the hand were stimulated on both the symptomatic and not symptomatic side in all patients. The LEPs were recorded by 25 scalp electrodes During attacks, the P2 wave was significantly enhanced; the amplitude of the P2 component obtained by the stimulation of the supraorbital zone during the attack on the side of the headache was significantly correlated with the intensity of pain and the frequency of headache. Both almotriptan and lysine acetyl-salicylate significantly reduced the P2 amplitude but they showed no effects on hyperalgesia to laser stimulation; headache relief following therapy was correlated with the reduction of the P2 amplitude. The cortical elaboration of laser-induced experimental pain seemed increased during migraine attack, and the severity of headache was mainly related to the increase of the later LEPs components expressing the attentive and emotive compounds of suffering. Reversion of this process appeared to be primarily responsible for the efficacy of drugs in treating migraine, though both almotriptan and lysine-acetil salicilate seemed to have no effect in reducing sensitization at second and third order nociceptive neurons.