Summary
Platelets are involved in the clinical presentations of ischemic heart disease. Our
objective was to study the antithrombotic effects of a new nitric oxide donor (LA419),
a neutral sugar organic nitrate with a protected thiol group in its molecular structure.
Animals were randomly distributed in three groups: I) oral administration of LA419
(0.9-1.8-3.6-5 mg/kg/d, 10 days); II) oral administration of standard IS-5-MN (0.9-1.8
mg/kg/d, 10 days); III) non-treated group (control). In catheterized pigs, thrombosis
was studied under controlled rheological condi- tions by radioisotopic evaluation
of deposited platelets on damaged vessel wall, placed in an extracorporeal perfusion
chamber. Changes in blood pressure, heart rate, and platelet aggregation were evaluated.
Results have shown that LA419 significantly decreased thrombus formation according
to the degree of vascular damage, and shear rate conditions in a dose- dependent manner
(p<0.005), without significant modifications on blood pressure and/or elevation of
liver enzymes. In contrast, IS-5-MN only showed a significant reduction on plate-
let deposition at the high dose, that was associated to hypoten- sion and elevation
of liver enzymes. Therefore, we conclude that this new anti-ischemic NO-donor (NOd)
LA419 that inhibits platelet function without modifying blood pressure may be a highly
efficacious strategy to passivate platelet activation induced by a damaged vessel
wall.
Keywords
Platelets - thrombosis - nitric oxide - blood pressure - pigs
