Nitric oxide-donating aspirin (NCX 4016) inhibits neointimal thickening in a pig model of saphenous vein-carotid artery interposition grafting: a comparison with aspirin and morpholinosydnonimine (SIN-1).
OBJECTIVE
Despite its proven value in reducing thrombotic complications in patients undergoing coronary artery bypass graft surgery, aspirin does not reduce the incidence of late vein graft failure. It was suggested, therefore, that co-administration of nitric oxide with aspirin may compensate for these limitations. A drug class that fulfills this pharmacologic criterion is nitric oxide-donating aspirin (NCX 4016).


METHODS
The effect of administration of the aspirin-nitric oxide adduct, NCX 4016, compared with those of aspirin alone and the nitric oxide donor, morpholinosydnonimine, alone (once daily for 1 month) on thickening of saphenous vein-carotid artery interposition grafts was investigated.


RESULTS
NCX 4016, at 10 mg, 30 mg, and 60 mg x kg(-1) x d(-1), inhibited neointimal thickness and area in porcine vein grafts. Aspirin alone (60 mg x kg(-1) x d(-1)) and morpholinosydnonimine alone (1 mg x kg(-1) x d(-1)), also inhibited neointimal thickness and neointimal area, although they were less potent than NCX 4016. At 30 mg x kg(-1) x d(-1), aspirin had no effect. Compared with untreated controls, NCX 4016 had little effect on medial thickness or area at 10 mg/kg or 30 mg x kg(-1) x d(-1) but had a significant effect at 60 mg x kg(-1) x d(-1). Aspirin alone and morpholinosydnonimine alone also inhibited medial thickness and area. NCX 4016 at 60 mg x kg(-1) x d(-1) and aspirin at 60 mg x kg(-1) x d(-1) increased luminal area.


CONCLUSIONS
The range of properties displayed by NCX 4016 (inhibition of neointima formation, gastroprotection, antithrombotic and antiatherogenic effects) renders them potentially useful in treating both early and late vein graft failure and indicates that a clinical study on this novel drug class in patients undergoing coronary bypass grafting is warranted.
Wan
Song
S
Department of Surgery, Prince of Wales Hospital, Chinese University of Hong Kong, Hong Kong, China.
Shukla
Nilima
N
Angelini
Gianni D
GD
Yim
Anthony P C
AP
Johnson
Jason L
JL
Jeremy
Jamie Y
JY
D000284:Administration, Oral; D000704:Analysis of Variance; D000714:Anastomosis, Surgical; D000818:Animals; D001241:Aspirin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D002339:Carotid Arteries / Q000187:drug effects / Q000473:pathology / Q000637:transplantation*; D004305:Dose-Response Relationship, Drug; D006083:Graft Occlusion, Vascular / Q000517:prevention & control; D008297:Male; D008981:Molsidomine / Q000031:analogs & derivatives* / Q000494:pharmacology; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D012501:Saphenous Vein / Q000187:drug effects / Q000473:pathology / Q000637:transplantation*; D018709:Statistics, Nonparametric; D013552:Swine; D017539:Tunica Intima / Q000187:drug effects* / Q000473:pathology
D020030:Nitric Oxide Donors; C002385:linsidomine; D008981:Molsidomine; C102148:nitroaspirin; D001241:Aspirin