Effects on blood compatibility in vitro by combining a direct P2Y12 receptor inhibitor and heparin coating of stents.
The effect of the direct platelet P2Y12 receptor inhibitor, AR-C69931MX, on activation of blood induced by stents with and without heparin coating was investigated using a whole blood Chandler loop model in vitro. Stents were deployed in Chandler loops. Fresh human blood with heparin and AR-C69931MX was rotated for 1 h at 37 degrees C and used for measurements of platelets, microparticles, thrombin-antithrombin complex (TAT), fibrinogen binding to platelets, P-selectin expression by platelets, CD11b, Prothrombin Fragment F1+2, FXIa-AT, FXIIa-AT, C3a, sC5b-9 and stent score. In the first experiment there were four study groups with unmodified stents: 1a, no AR-C69931MX; 1b, 250 nmol/L; 1c, 750 nmol/L; 1d, 2250 nmol/L of AR-C69931MX. In the second experiment the concentration of AR-C69931MX was 500 nmol/L: 2a; tubings without stent; 2b; tubings with heparin-coated stent; 2c; tubings with unmodified stents. Heparin-coated stents were used in the third experiment: 3a; no AR-C69931MX; 3b; 500 nmol/L of AR-C69931MX. In the first experiment there were significant differences in all parameters analysed except for C3a, and stent score when the group with no AR-C69931MX was compared to all the groups with AR-C69931MX. In the second experiment there were significant differences in platelet count, TAT, FXIa-AT, FXIIa-AT and stent score when unmodified stents were compared to loops with no stents and partly to loops with heparin-coated stents. In the third experiment there was a significant reduction in generation of TAT, stent score and better preservation of platelet number by combining the platelet inhibitor and heparin-coated stents as compared to heparin-coated stents alone. The conclusion is that the direct P2Y12 receptor inhibitor AR-C69931MX reduced the different aspects of activation of blood induced by both unmodified and heparin-coated stents.
Christensen
Kjeld
K
Division of Cardiology, University Hospital, Orebro, Sweden. kjeld.christensen@orebroll.se
Larsson
Rolf
R
Emanuelsson
Håkan
H
Elgue
Graciela
G
Larsson
Anders
A
D000249:Adenosine Monophosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D000704:Analysis of Variance; D000925:Anticoagulants / Q000009:adverse effects / Q000494:pharmacology; D000990:Antithrombin III / Q000032:analysis; D001792:Blood Platelets / Q000378:metabolism*; D039481:CD11b Antigen / Q000187:drug effects / Q000378:metabolism*; D003167:Complement Activation / Q000187:drug effects; D016503:Drug Delivery Systems; D015956:Factor XIIa / Q000032:analysis; D015945:Factor XIa / Q000032:analysis; D005434:Flow Cytometry; D006493:Heparin / Q000008:administration & dosage / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000187:drug effects; D010447:Peptide Hydrolases / Q000032:analysis; D015539:Platelet Activation / Q000187:drug effects* / Q000502:physiology; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2 / Q000187:drug effects; D058925:Receptors, Purinergic P2Y12; D015607:Stents
D000925:Anticoagulants; D039481:CD11b Antigen; D008565:Membrane Proteins; C548576:P2RY12 protein, human; D010975:Platelet Aggregation Inhibitors; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2; D058925:Receptors, Purinergic P2Y12; C046193:antithrombin III-protease complex; D000249:Adenosine Monophosphate; C117446:cangrelor; D000990:Antithrombin III; D006493:Heparin; D010447:Peptide Hydrolases; D015945:Factor XIa; D015956:Factor XIIa