A human model of platelet-leucocyte adhesive interactions during controlled ischaemia in patients with peripheral vascular disease.
OBJECTIVE
In humans, little is known about the effects of platelet-leucocyte interactions on blood viscosity and microvascular perfusion. This study tested the hypotheses that (1) activation and interactions between platelets and leucocytes may have an impact on microvascular blood viscosity and perfusion in patients with stage II peripheral arterial occlusive disease, and (2) a powerful antiplatelet drug such as Clopidogrel might help to improve microvascular perfusion by reducing platelet-leucocyte activation and blood viscosity.


METHODS
Plasma concentrations of certain markers of leucocyte and platelet activation, in addition to low and high shear rate blood viscosity, were measured before and after a repeated exercise treadmill test. Functional parameters including maximum walking time, transcutaneous oxygen pressure, and half recovery time were also measured.


RESULTS
Blocking platelet activation only with a single dose of Clopidogrel (300 mg) did not improve microvascular blood viscosity and perfusion after repeated exercise, but a significant improvement in microvascular perfusion during controlled ischaemia and a lack of post exercise increase in low shear rate blood viscosity was achieved when both platelet and leucocyte activation were suppressed by a relatively longer treatment with Clopidogrel (four days).


CONCLUSIONS
Clopidogrel, by inhibiting platelet activation and aggregation, might also block the vicious cycle of leucocyte-platelet activation, thus improving the functioning of the microcirculation.
Pasqualini
L
L
Internal Medicine, Angiology and Arteriosclerosis Disease Clinic, Department of Clinical and Experimental Medicine, University of Perugia, 06122 Perugia, Italy.
Pirro
M
M
Lombardini
R
R
Ciuffetti
G
G
Dragani
P
P
Mannarino
E
E
D000328:Adult; D001157:Arterial Occlusive Diseases / Q000097:blood* / Q000188:drug therapy / Q000503:physiopathology; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D001809:Blood Viscosity / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects; D000077144:Clopidogrel; D004311:Double-Blind Method; D005080:Exercise Test; D006801:Humans; D007962:Leukocytes / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D008875:Middle Aged; D010100:Oxygen / Q000097:blood; D010313:Partial Pressure; D016491:Peripheral Vascular Diseases / Q000097:blood* / Q000188:drug therapy / Q000503:physiopathology; D015539:Platelet Activation / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine; D010100:Oxygen