Purpose: Current antiplatelet therapies, designed primarily to modulate biochemical pathways of platelet activation (PA), have been poorly studied in ventricular assist devices VADs. The aim of this work is to test platelet inhibition efficacy of different kinds of anti-platelet agents, such as aspirin (acetylsalicylic acid, ASA) and ticagrelor under controlled and VAD-like shear stress conditions. Methods: Gel filtered-platelets (GFP) was obtained upon collection of blood from healthy adult volunteers. GFP was subjected to constant shear stress in both physiological (3 Pa) and supraphysiological (7 Pa) ranges and also to a dynamic shear stress emulating the shear pattern of the DeBakey VAD. The hemodynamic shearing device, a cone-plate and Couette computer-controlled viscometer, was used to subject platelets to the different shear stress conditions. To evaluate antiplatelet drug efficacy, either GFP alone and GFP incubated for 10 min with drug solutions (ASA 25 and 125 uM, ticagrelor 10 and 100 uM) was tested. Samples were collected at different time points up to 10 min of shear and tested for PA through the platelet activity state (PAS) assay. Results: Results revealed that ASA is able to inhibit PA only at lower shear levels (3 Pa) under constant shear condition, and it didn't show any effect on the VAD-like shear condition. Conversely, ticagrelor showed a significant inhibition effect in all the different shearing conditions. In particular, a higher concentration (100 uM) was necessary to obtain significant inhibition under VAD-like shear condition. Conclusion: We demonstrated that anti-platelet agents effect is very dependent on the shear conditions that platelets experience. We also showed that ticagrelor provides a significant protection from shear-induced PA, while the effect of ASA was not achieved at either high constant shear and dynamic VAD-like conditions, suggesting that the latter may have a very limited efficacy in vivo in patients implanted with such devices.
Anti-Platelet Drug Efficacy In Vitro Under VAD-Like Shear Stress Conditions
CONSOLO, FILIPPO;
2017-01-01
Abstract
Purpose: Current antiplatelet therapies, designed primarily to modulate biochemical pathways of platelet activation (PA), have been poorly studied in ventricular assist devices VADs. The aim of this work is to test platelet inhibition efficacy of different kinds of anti-platelet agents, such as aspirin (acetylsalicylic acid, ASA) and ticagrelor under controlled and VAD-like shear stress conditions. Methods: Gel filtered-platelets (GFP) was obtained upon collection of blood from healthy adult volunteers. GFP was subjected to constant shear stress in both physiological (3 Pa) and supraphysiological (7 Pa) ranges and also to a dynamic shear stress emulating the shear pattern of the DeBakey VAD. The hemodynamic shearing device, a cone-plate and Couette computer-controlled viscometer, was used to subject platelets to the different shear stress conditions. To evaluate antiplatelet drug efficacy, either GFP alone and GFP incubated for 10 min with drug solutions (ASA 25 and 125 uM, ticagrelor 10 and 100 uM) was tested. Samples were collected at different time points up to 10 min of shear and tested for PA through the platelet activity state (PAS) assay. Results: Results revealed that ASA is able to inhibit PA only at lower shear levels (3 Pa) under constant shear condition, and it didn't show any effect on the VAD-like shear condition. Conversely, ticagrelor showed a significant inhibition effect in all the different shearing conditions. In particular, a higher concentration (100 uM) was necessary to obtain significant inhibition under VAD-like shear condition. Conclusion: We demonstrated that anti-platelet agents effect is very dependent on the shear conditions that platelets experience. We also showed that ticagrelor provides a significant protection from shear-induced PA, while the effect of ASA was not achieved at either high constant shear and dynamic VAD-like conditions, suggesting that the latter may have a very limited efficacy in vivo in patients implanted with such devices.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
