SIN-1 reduces platelet adhesion and platelet thrombus formation in a porcine model of balloon angioplasty.
BACKGROUND
Nitric oxide inhibits platelet adhesion and platelet aggregation in vivo. In this study, we investigated the effects of the nitric oxide donor SIN-1 on platelet adhesion and platelet-thrombus formation following experimental angioplasty.


RESULTS
Bilateral carotid angioplasty was performed in 20 anesthetized pigs. Animals received either SIN-1 (3-morpholino-sydnonimine; 10 micrograms/kg/min; n = 8) or placebo (n = 8) before and during angioplasty. An additional control group of pigs received trimetaphan (n = 4), which induced hemodynamic changes similar to those that followed treatment with SIN-1. Platelet deposition was quantified by the injection of autologous 111In-labeled platelets. SIN-1 reduced platelet deposition after deep arterial injury compared with placebo (mean +/- SEM, 10.870 +/- 2.415 versus 40.326 +/- 9.889 platelets x 10(6)/cm2, p < 0.05). SIN-1 reduced platelet adhesion after superficial injury compared with both placebo and trimetaphan (2.231 +/- 0.333 versus 5.278 +/- 0.606 versus 5.022 +/- 1.136 platelets x 10(6)/cm2, respectively; p < 0.005). Scanning electron microscopy confirmed that platelets were deposited in the form of an adherent monolayer following superficial endothelial denudation and were reduced in number following treatment with SIN-1. The effects of SIN-1 on platelet function were associated with a significant increase in platelet cyclic GMP concentration from baseline (3.15 +/- 0.88 versus 1.58 +/- 0.73 pmol/10(9) platelets, p < 0.005).


CONCLUSIONS
SIN-1 reduces platelet adhesion and platelet-thrombus formation following experimental angioplasty. The antiadhesive effects of SIN-1 are independent of changes in systemic hemodynamics. These results imply that the administration of a nitric oxide donor may prove effective in modifying the pathophysiological response to angioplasty injury.
Groves
P H
PH
Department of Cardiology, University of Wales College of Medicine, Cardiff, UK.
Lewis
M J
MJ
Cheadle
H A
HA
Penny
W J
WJ
D000800:Angioplasty, Balloon; D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects*; D006439:Hemodynamics; D008855:Microscopy, Electron, Scanning; D008981:Molsidomine / Q000031:analogs & derivatives* / Q000494:pharmacology; D010973:Platelet Adhesiveness / Q000187:drug effects*; D010979:Platelet Function Tests
C002385:linsidomine; D008981:Molsidomine