Further studies on the mechanism for the antithrombotic effects of naroparcil, an orally active thiozyloside compound.

The antithrombotic beta-D-xyloside, naroparcil, has previously been shown to induce a dose-related increase of circulating glycosaminoglycans (GAGs) together with an antithrombin activity (anti-IIa) via heparin cofactor II (HCII) in the rabbit. In order to go further in the mechanisms, the relationship between the antithrombotic activity, the HCII-mediated anti-IIa activity and the plasma GAG content was investigated. We showed that the in vitro specific activity on the inhibition of thrombin by HCII of the plasma GAG extract from naroparcil-treated rabbits was increased by a factor of 60 when compared to controls.

The effect of the beta-D-xyloside naroparcil on circulating plasma glycosaminoglycans. An explanation for its known antithrombotic activity in the rabbit.

Beta-D-Xylosides are known to initiate or prime free glycosaminoglycan (GAG) chain synthesis in cell and tissue culture. As such, the effect of the venous antithrombotic beta-D-xyloside, naroparcil, was investigated on the plasma GAG profile in the rabbit after oral administration. Using dose-response experiments, we showed that antithrombin activity via antithrombin III and heparin cofactor II was increased in parallel with GAG plasma levels compared to control.

[The effect of slight to moderate stenoses on the coronary reserve and hemodynamics].

The effect of slight to moderate stenosis (less than or equal to 50% of external diameter) on the coronary reserve and coronary hemodynamics has been studied in 8 pigs. The coronary reserve was measured by the technique of reactive hyperemia, which consists of brief total occlusion of the artery concerned and sudden relaxation. The decrease in coronary reserve is directly proportional to the degree of stenosis.