Digoxin and Platelet Activation in Patients With Atrial Fibrillation: In Vivo and In Vitro Study

Figures

• 

  Figure 1. Comparison of in vivo digoxin‐induced platelet activation in HS and patients with AF. A, [Ca2+]i mobilization in platelets incubated with or without digoxin alone (2.4 ng/mL) in patients with AF (n=3) or HS (n=5) (*P<0.001). B, glycoprotein IIb/IIIa expression (PAC‐1) in platelets incubated with or without digoxin (2.4 ng/mL) in patients with AF (n=3) or HS (n=5) (*P<0.001). C, Platelet aggregation in platelet‐rich plasma incubated with or without digoxin (2.4 ng/mL) in patients with AF (n=3) or HS (n=5) (*P<0.001). AF indicates atrial fibrillation; HS, healthy subjects; PAC‐1, procaspase‐activating compound 1.

• 

  Figure 2. In vitro digoxin‐induced platelet activation in HS. A, [Ca2+]i mobilization in platelets incubated with digoxin alone (2.4 ng/mL) or prestimulated with an STC of collagen (0.25 μg/mL) and activated with scalar concentrations of digoxin (0.6–2.4 ng/mL) or ouabain in the presence or not of antibody against digoxin or EDTA (*P<0.05, **P<0.001, n=3 experiments). B, IIb/IIIb expression (PAC‐1) in platelets incubated with scalar concentrations of digoxin (0.6–2.4 ng/mL) or ouabain and prestimulated with an STC of collagen (0.25 μg/mL) in the presence or not of antibody against digoxin, EDTA, or AACOCF3 (n=3 experiments) (*P<0.05, **P<0.001). C, Platelet aggregation in platelet‐rich plasma incubated with digoxin alone (2.4 ng/mL) or prestimulated with an STC of collagen (0.25 μg/mL) and activated with scalar concentrations of digoxin (0.6–2.4 ng/mL) or ouabain and in the presence or not of antibody against digoxin, EDTA, or AACOCF3 (n=5 experiments) (*P<0.05, **P<0.001). D, Representative tracing of platelet aggregation. AACOCF3 indicates arachidonyl trifluoromethyl ketone; EDTA, ethylenediaminetetraacetic acid; HS, healthy subjects; PAC‐1, procaspase‐activating compound 1; STC,…

• 

  Figure 3. Mechanisms of digoxin‐induced platelet activation. A, 11‐dehydro‐TxB2 production from platelets incubated with scalar concentrations of digoxin (0.6–2.4 ng/mL) or ouabain and prestimulated with an STC of collagen (0.25 μg/mL) in the presence or not of antibody against digoxin, EDTA, or AACOCF3 (n=5 experiments in healthy subjects) (*P<0.05, **P<0.001). B, sP‐selectin release in platelets incubated with scalar concentrations of digoxin (0.6–2.4 ng/mL) or ouabain and prestimulated with an STC f collagen (0.25 μg/mL) in the presence or not of antibody against digoxin, EDTA, or AACOCF3 (n=3 experiments) (*P<0.05, **P<0.001). C, cPLA 2 phosphorylation was analyzed in platelets incubated with digoxin alone (2.4 ng/mL) or prestimulated with an STC of collagen (0.25 μg/mL) and activated with scalar concentrations of digoxin (0.6–2.4 ng/mL) or ouabain in the presence or not of antibody against digoxin, EDTA, or AACOCF3 (*P<0.05, **P<0.001; n=3 experiments in healthy subjects). D, Arachidonic acid production in platelets incubated with digoxin alone (2.4 ng/mL) or prestimulated with an STC of collagen (0.25 μg/mL) and activated with scalar concentrations of digoxin (0.6–2.4 ng/mL) or…