Xenon Antiaggregant Effects
V V Udut1,2, D V Tsuran1, S A Naumov1
1E. D. Goldberg Research Institute of Pharmacology and Regenerative Medicine, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk, Russia.
Abstract:
In in vitro model of short-term therapeutic inhalation of Xe/O2 mixture, xenon in millimolar concentrations led to a pronounced decrease in induced platelet aggregation in the platelet-enriched blood plasma. The maximum and statistically significant decrease occurred in response to induction by collagen (by ≈30%, p≤0.01) and ADP (by ≈25%, p≤0.01). A slightly weaker but statistically significant reduction in aggregation appeared in response to ristocetin (by ≈12%, p≤0.01) and epinephrine (by ≈9%, p≤0.01). It should be noted that the spontaneous aggregation exceeded the reference values in the control group. Nevertheless, even at minimal absolute values, spontaneous platelet aggregation decreased by 2 times in response to xenon (p≤0.01). The reasons for the decrease of spontaneous and induced aggregation are xenon accumulation in the lipid bilayer of the membrane with subsequent nonspecific (mechanical) disassociation of membrane platelet structures and specific block of its distinct from neuronal NMDA receptor.
Insights
Xenon gas (Xe) significantly reduces platelet aggregation, both spontaneous and induced by common agonists. This finding suggests potential therapeutic applications for xenon in managing platelet-related conditions.
Area of Science:
- Biochemistry
- Pharmacology
- Hematology
Background:
- Platelet aggregation plays a crucial role in hemostasis and thrombosis.
- Disruptions in platelet function are implicated in various cardiovascular and bleeding disorders.
- Novel therapeutic agents targeting platelet activity are continuously sought.
Purpose of the Study:
- To investigate the in vitro effects of xenon (Xe) on platelet aggregation.
- To determine the impact of xenon on spontaneous and agonist-induced platelet aggregation.
Main Methods:
- An in vitro model using platelet-enriched blood plasma.
- Induction of platelet aggregation using collagen, ADP, ristocetin, and epinephrine.
- Measurement of platelet aggregation in the presence of millimolar concentrations of xenon.
Main Results:
- Xenon significantly decreased collagen-induced (≈30%) and ADP-induced (≈25%) platelet aggregation.
- Xenon also reduced ristocetin-induced (≈12%) and epinephrine-induced (≈9%) aggregation.
- Spontaneous platelet aggregation was decreased twofold by xenon.
Conclusions:
- Xenon exhibits potent anti-aggregatory effects on platelets in vitro.
- Xenon's mechanism may involve membrane lipid interactions and NMDA receptor blockade.
- These findings highlight xenon's potential as a therapeutic agent for platelet dysfunction.
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