PLATELET INHIBITION WITH CLOPIDOGREL AUGMENTS CUTANEOUS REACTIVE HYPEREMIA IN HEALTHY, MIDDLE-AGED SKIN
Open Access
- Author:
- Dahmus, Jessica Dorothy
- Area of Honors:
- Kinesiology
- Degree:
- Bachelor of Science
- Document Type:
- Thesis
- Thesis Supervisors:
- William Lawrence Kenney Jr., Thesis Supervisor
Lacy Alexander Holowatz, Thesis Supervisor
William Lawrence Kenney Jr., Thesis Supervisor
Stephen Jacob Piazza, Thesis Honors Advisor - Keywords:
- thermoregulation
skin blood flow
platelets
reactive hyperemia - Abstract:
- Daily low-dose aspirin (ASA, 81 mg) therapy is the gold standard for primary and secondary prevention of atherothrombotic disease. Clopidogrel (Plavix®, 75 mg) is the second most widely used prescription drug in the world for secondary atherothrombotic disease treatment. ASA and clopidogrel inhibit platelet function through cyclooxygenase- (COX) and ADP-receptor inhibition, respectively. Reflex cutaneous vasodilation (VD) is significantly impaired in humans taking ASA and clopidogrel via independent mechanisms. However, the impact of platelet inhibition on whole blood viscoelastic properties and their influence on shear-induced VD is unknown. We hypothesized that systemic low-dose aspirin and clopidogrel each would attenuate shear-induced cutaneous vasodilation by lowering whole-blood viscosity. Five healthy men and women (55±3 years) were orally-administered aspirin (81mg), clopidogrel (75mg), or placebo for 7 days in a double-blind fashion with 2 weeks of washout between treatments. A reactive hyperemia protocol was performed, utilizing bretylium-tosylate iontophoresis on one site to inhibit sympathetic adrenergic function. Skin blood flow was measured using laser-Doppler (LD) flowmetry. Cutaneous vascular conductance was calculated (CVC=LDF/MAP). Data were normalized to maximal CVC (%CVCmax: local heat to 43°C). Clopidogrel significantly increased VD through augmented area under the curve (AUC) measurements (AUCclopidogrel = 4187 ± 376 %CVCmax•s vs. Control AUC = 3559 ± 259 %CVCmax•s) (p<0.05), but there was no change with ASA (AUCASA = 3523 ± 481 %CVCmax•s). Total hyperemic response (THR) values approached significance between clopidogrel and placebo (p=0.068). Contrary to our hypothesis, clopidogrel augmented cutaneous reactive hyperemia, indicating that platelet ADP-receptor inhibition may improve endothelial function in the cutaenous microvasculature.