S-nitrosoglutathione inhibits platelet activation and deposition in coronary artery saphenous vein grafts in vitro and in vivo.
OBJECTIVE
To investigate platelet activation and deposition in human saphenous vein and internal mammary artery grafts following coronary artery bypass in vitro and in vivo, as well as inhibition of activation by the platelet selective nitric oxide donor S-nitrosoglutathione (GSNO).


METHODS
Controlled in vitro and in vivo studies.


METHODS
Tertiary cardiac centre.


METHODS
24 patients undergoing coronary artery bypass surgery requiring vein and artery grafts.


METHODS
In vitro: human platelet rich plasma was perfused through segments of vein and artery, with or without GSNO 10(-6) M, and the platelet count was measured in the effluent. In vivo: indium-111 labelled antibody against the platelet alpha granule protein GMP-140 was injected at the end of coronary bypass grafting and gamma counts were compared between vein and artery grafts with or without systemic infusion of GSNO (40 nmol/min).


RESULTS
In vitro: platelet count in perfused vein (< 70% of baseline) decreased more than in artery segments (89-94% of baseline) (p < 0.001). The platelet count was unchanged with GSNO in vein and artery segments. In vivo: gamma counts were greater at all time points over vein than artery grafts (p < 0.05), and were reduced by infusion of GSNO (p < 0.05).


CONCLUSIONS
Platelet activation is greater in vein than in artery grafts in vitro and in vivo. Activation, which contributes to early vein graft failure, was inhibited by GSNO.
Salas
E
E
Department of Gynecology, Obstetrics and Pharmacology, University of Alberta, Edmonton, Canada.
Langford
E J
EJ
Marrinan
M T
MT
Martin
J F
JF
Moncada
S
S
de Belder
A J
AJ
D000368:Aged; D000911:Antibodies, Monoclonal; D001026:Coronary Artery Bypass; D003327:Coronary Disease / Q000601:surgery; D005260:Female; D005978:Glutathione / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D006083:Graft Occlusion, Vascular / Q000517:prevention & control; D006801:Humans; D007205:Indium Radioisotopes; D008297:Male; D008875:Middle Aged; D009204:Myocardial Revascularization; D009603:Nitroso Compounds / Q000494:pharmacology* / Q000627:therapeutic use; D019007:P-Selectin / Q000276:immunology; D015539:Platelet Activation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D026422:S-Nitrosoglutathione; D012501:Saphenous Vein / Q000637:transplantation*
D000911:Antibodies, Monoclonal; D007205:Indium Radioisotopes; D009603:Nitroso Compounds; D019007:P-Selectin; D010975:Platelet Aggregation Inhibitors; D026422:S-Nitrosoglutathione; D005978:Glutathione