Inhibition of thrombosis by a novel platelet selective S-nitrosothiol compound without hemodynamic side effects

Abstract

Platelet and endothelial production of bioactive nitric oxide (NO) is known to be impaired in acute coronary syndromes, thus compounds that release NO are useful candidates to restore NO-vascular functions. Objective: We have studied whether donation of NO with a novel platelet-selective S-nitrosothiol compound (LA810) at a systemic level can inhibit thrombosis elicited by damaged vessel wall (eroded and disrupted vessel wall) at hemodynamic conditions typical of patent and stenotic coronary arteries. Methods: Thrombogenicity was measured in the porcine experimental model and assessed as platelet–thrombus formation in the ex vivo Badimon perfusion chamber. After baseline perfusions, female pigs (Large White × Landrace) were given intravenous infusion of LA810 or GSNO standard S-nitrosothiol during 2 h. Changes in blood pressure, heart rate and in vitro platelet aggregation were measured. Results: LA810 significantly decreased thrombus formation at any degree of vascular damage and shear rate (pConclusions: This new anti-ischemic NO-donor (NOd) LA810 that inhibits platelet function without hypotensive side-effects seems a highly efficacious strategy to reduce acute thrombosis triggered by coronary artery disease.