Selected Publication:

SHR Neuro Cancer Cardio Lipid Metab Microb

Tsiountsioura, M; Cvirn, G; Schlagenhauf, A; Haidl, H; Zischmeier, K; Janschitz, N; Koestenberger, M; Wonisch, W; Paar, M; Wagner, T; Weiss, EC; Hallström, S.
The Antiplatelet Action of S-Nitroso Human Serum Albumin in Whole Blood.
Biomedicines. 2022; 10(3): Doi: 10.3390/biomedicines10030649 [OPEN ACCESS]
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Leading authors Med Uni Graz

Cvirn Gerhard

Co-authors Med Uni Graz

Haidl Harald

Hallström Seth

Koestenberger Martin

Paar Margret

Schlagenhauf Axel

Wagner Thomas

Weiss Eva Christine

Wonisch Willibald

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Abstract:

Nitric oxide donors (NO-donors) have been shown to have therapeutic potential (e.g., ischemia/reperfusion injury). However, due to their release rate/antiplatelet properties, they may cause bleeding in patients. We therefore studied the antiplatelet effects of the two different NO-donors, i.e., S-NO-Human Serum Albumin (S-NO-HSA) and Diethylammonium (Z)-1-(N,N-diethylamino)diazen-1-ium-1,2-diolate (DEA-NONOate) in whole blood (WB) samples. WB samples were spiked with S-NO-HSA or DEA-NONOate (100 µmol/L or 200 µmol/L), and the NO release rate (nitrite/nitrate levels via HPLC) and antiplatelet efficacy (impedance aggregometry, platelet function analyzer, Cone-and-platelet analyzer, thrombelastometry) were assessed. S-NO-HSA had a significantly lower NO release compared to equimolar concentrations of DEA-NONOate. Virtually no antiplatelet action of S-NO-HSA was observed in WB samples, whereas DEA-NONOate significantly attenuated platelet function in WB. Impedance aggregometry measurements revealed that Amplitudes (slope: -0.04022 ± 0.01045 ohm/µmol/L, p = 0.008) and Lag times (slope: 0.6389 ± 0.2075 s/µmol/L, p = 0.0051) were dose-dependently decreased and prolonged by DEA-NONOate. Closure times (Cone-and-platelet analyzer) were dose-dependently prolonged (slope: 0.3738 ± 0.1403 s/µmol/L, p = 0.0174 with collagen/ADP coating; slope: -0.5340 ± 0.1473 s/µmol/L, p = 0.0019 with collagen/epinephrine coating) by DEA-NONOate. These results in WB further support the pharmacological potential of S-NO-HSA as an NO-donor due to its ability to presumably prevent bleeding events even at high concentrations up to 200 µmol/L.

Find related publications in this database (Keywords)

nitric oxide donors

platelet function

impedance aggregometry

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