Prothrombotic responses to exercise are little influenced by clopidogrel treatment.
OBJECTIVE
Adenosine diphosphate (ADP) is involved in shear-induced platelet activation, which may be important for platelet responses to stress. We therefore tested the hypothesis that ADP receptor antagonism by clopidogrel treatment would attenuate exercise-induced platelet activation.


RESULTS
Fifteen healthy volunteers performed exhaustive exercise without and with clopidogrel pretreatment (75 mg/day; 7 days) in a randomised crossover study. Filtragometry readings (reflecting platelet aggregability in vivo) and 11-dehydro-thromboxane B(2) (TxM) in plasma were determined before and after exercise. Platelet and leukocyte activity, platelet-platelet (PPA), and platelet-leukocyte aggregates (PLAs) in vivo and their responsiveness to agonist stimulation in vitro were assessed by flow cytometry. Clopidogrel treatment inhibited ADP-induced platelet P-selectin expression by 72% (54-85%). Exercise increased platelet aggregation (filtragometry and PPAs), elevated plasma TxM, increased single platelet P-selectin expression, elevated circulating PLAs, and enhanced ADP and thrombin-stimulated P-selectin expression. Clopidogrel prolonged filtragometry readings and attenuated agonist stimulated P-selectin expression at rest, but did not influence TxM in plasma or urine or attenuate platelet or leukocyte responses to exercise. Clopidogrel treatment did not influence plasma CD40L (ligand) at rest or after exercise.


CONCLUSIONS
Clopidogrel treatment attenuates platelet activity in vivo at rest, but exercise counteracts the platelet stabilizing effects of clopidogrel. The hypothesis that ADP is involved in stress-induced platelet activation was not supported.
Perneby
C
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Clinical Pharmacology Unit, Department of Medicine, Karolinska University Hospital and Institute, Stockholm 171 76, Sweden.
Wallén
N H
NH
Hu
H
H
Li
N
N
Hjemdahl
P
P
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000328:Adult; D001792:Blood Platelets / Q000737:chemistry / Q000166:cytology; D002448:Cell Adhesion; D000077144:Clopidogrel; D018592:Cross-Over Studies; D015444:Exercise / Q000502:physiology*; D006801:Humans; D007962:Leukocytes / Q000166:cytology; D008297:Male; D019007:P-Selectin / Q000032:analysis; D010974:Platelet Aggregation; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D019851:Thrombophilia / Q000188:drug therapy* / Q000209:etiology; D013929:Thromboxane B2 / Q000031:analogs & derivatives* / Q000097:blood / Q000652:urine; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*
D019007:P-Selectin; D010975:Platelet Aggregation Inhibitors; D013929:Thromboxane B2; D000244:Adenosine Diphosphate; C049235:11-dehydro-thromboxane B2; D000077144:Clopidogrel; D013988:Ticlopidine