SIN-1 reduces platelet adhesion and platelet thrombus formation in a porcine model of balloon angioplasty

Abstract

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. Methods and Results. Bilateral carotid angioplasty was performed in 20 anesthetized pigs. Animals received either SIN-1 (3-morpholino-sydnonimine; 10 μg/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×106/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×106/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/109 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.