Reference : Effect of BM-573[N-terbutyl-N '-[2-(4 '-methylphenylamino)-5-nitro-benzenesulfonyl] u...
Scientific journals : Article
Human health sciences : Pharmacy, pharmacology & toxicology
Effect of BM-573[N-terbutyl-N '-[2-(4 '-methylphenylamino)-5-nitro-benzenesulfonyl] urea], a dual thromboxane synthase inhibitor and thromboxane receptor antagonist, in a porcine model of acute pulmonary embolism
Ghuysen, Alexandre mailto [Université de Liège - ULiège > Département des sciences de la santé publique > Réanimation - Urgence extrahospitalière]
Lambermont, Bernard mailto [Centre Hospitalier Universitaire de Liège - CHU > > Frais communs médecine >]
Dogné, Jean-Michel [Université de Liège - ULiège > Département de pharmacie > Département de pharmacie >]
Kolh, Philippe mailto [Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Service de biochimie et de physiologie humaines, normale et pathologique > >]
Tchana-Sato, Vincent [Centre Hospitalier Universitaire de Liège - CHU > > Chirurgie cardio-vasculaire >]
Morimont, Philippe mailto [Centre Hospitalier Universitaire de Liège - CHU > > Frais communs médecine >]
Magis, David mailto [Université de Liège - ULiège > Département de mathématique > Département de mathématique >]
Hanson, Julien mailto [Université de Liège - ULiège > > Chimie pharmaceutique >]
Segers, P. [> > > >]
D'Orio, Vincenzo mailto [Université de Liège - ULiège > Département des sciences cliniques > Médecine d'urgence - bioch. et phys. hum. normales et path.]
Journal of Pharmacology and Experimental Therapeutics (The)
Amer Soc Pharmacology Experimental Therapeutics
Yes (verified by ORBi)
[en] The aim of this study was to evaluate the effect of BM-573 [N-terbutyl-N'-[2-(4'-methylphenylamino)-5-nitro-benzenesulfonyl] urea], a dual thromboxane A(2) synthase inhibitor and receptor antagonist, on the hemodynamic response to acute pulmonary embolism. Six anesthetized pigs were infused with placebo ( placebo group) and compared with six other pigs receiving a continuous infusion of BM-573 ( BM group). Pulmonary embolization with 0.3 g/kg autologous blood clots was carried out 30 min after the start of the infusion. Right ventricular pressure-volume loops were recorded using a conductance catheter, and end-systolic ventricular elastance was periodically assessed by varying right ventricular preload. Pulmonary vascular properties were studied by use of a four-element wind-kessel model. Hemodynamic data, including assessment of right ventricular-arterial coupling, were collected at baseline and every 30 min for 4 h. Blood samples were collected to assess gas exchange, thromboxane A(2), and prostacyclin plasma levels and to evaluate platelet aggregation. Mean pulmonary arterial pressure in the placebo group increased significantly more than in the BM group, mainly because of an additional increase in pulmonary vascular resistance. Arterial and end-systolic ventricular elastances increased also more in the placebo group, whereas right ventricular efficiency decreased. BM-573 prevented both platelet aggregation induced by U-46619 (9,11-dideoxy-11alpha, 9alpha-epoxymethanoprostaglandin F-2alpha) or by arachidonic acid, and thromboxane A(2) overproduction, whereas prostacyclin liberation was preserved. Oxygenation, however, was not significantly improved. We conclude that in this animal model of acute pulmonary embolism, infusion of BM-573 reduced pulmonary vasoconstriction. As a result, right ventricular-vascular coupling values were maintained at a maximal efficiency level.

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