Antithrombotic effect of a new nitric oxide donor (LA419) on experimental thrombogenesis.
BACKGROUND
The ability of nitrous compounds to donate nitric oxide (NO), an agent with vasodilating and inhibitory effects on platelet function, has been considered a useful pharmacologic strategy for cardiovascular complications. The purpose of this study was to investigate the effects of a new NO donor, LA419, on platelet interaction in an ex vivo model with human blood circulating through collagen-rich surfaces.


METHODS
Platelet adhesive and cohesive function were analyzed by morphometric procedures after perfusion techniques. Treated blood was exposed to thrombogenic surfaces and platelet interactions were morphometrically evaluated.


RESULTS
All the concentrations studied of LA419 (10 microM, 20 microM and 100 microM) reduced overall platelet interaction with a collagen surface (27.19 +/- 4.72; 25.52 +/- 3.52; and 23.44 +/- 3.01, P < 0.05, respectively, vs. 32.31 +/- 1.61% in the control). The antithrombotic effect was confirmed by results in cross-sectional studies performed in arterial vessels exposed to circulating blood. Values of thrombus and covered surface at 20 microM LA419 were, respectively, 13.67 +/- 4.97% and 19.01 +/- 5.89%; respect to controls 34.80 +/- 5.29% and 37.93 +/- 5.34% (P < 0.05). Moreover, LA419 reduced significantly thrombus area (88.45 +/- 21.97 microm(2); P < 0.05) with respect to controls (168.45 +/- 21.97 microm(2)) and thrombus height, from an average of 10.27 +/- 1.05 microm in nontreated blood to 7.16 +/- 0.6 microm in treated samples (P < 0.05).


CONCLUSIONS
From the present data we can conclude that LA419 possesses a strong antiplatelet action, as demonstrated by its ability to significantly inhibit the interaction of platelet with highly thrombogenic collagen surfaces.
Hernandez
M R
MR
Hospital Clínic i Provincial IDIBAPS, Departament de Medicina, Servei d' Hemoteràpia i Hemostàsia, Universitat de Barcelona, Barcelona, Spain. agalan@clinic.ub.es
Tonda
R
R
Arderiu
G
G
Pino
M
M
Serradell
M
M
Escolar
G
G
D000818:Animals; D001792:Blood Platelets / Q000187:drug effects* / Q000502:physiology; D003094:Collagen; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D006736:Horses; D006801:Humans; D007548:Isosorbide Dinitrate / Q000031:analogs & derivatives* / Q000494:pharmacology; D008954:Models, Biological; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D015539:Platelet Activation / Q000187:drug effects; D010973:Platelet Adhesiveness / Q000187:drug effects / Q000502:physiology; D011817:Rabbits; D013927:Thrombosis / Q000139:chemically induced* / Q000503:physiopathology
D005343:Fibrinolytic Agents; C503157:LA 419; D020030:Nitric Oxide Donors; D003094:Collagen; D007548:Isosorbide Dinitrate