Article (Scientific journals)
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; Lambermont, Bernard; Dogné, Jean-Michel et al.
2004In Journal of Pharmacology and Experimental Therapeutics, 310 (3), p. 964-972
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Abstract :
[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.
Disciplines :
Pharmacy, pharmacology & toxicology
Author, co-author :
Ghuysen, Alexandre ;  Université de Liège - ULiège > Département des sciences de la santé publique > Réanimation - Urgence extrahospitalière
Lambermont, Bernard  ;  Centre Hospitalier Universitaire de Liège - CHU > Frais communs médecine
Dogné, Jean-Michel ;  Université de Liège - ULiège > Département de pharmacie > Département de pharmacie
Kolh, Philippe  ;  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 ;  Centre Hospitalier Universitaire de Liège - CHU > Frais communs médecine
Magis, David ;  Université de Liège - ULiège > Département de mathématique > Département de mathématique
Hanson, Julien  ;  Université de Liège - ULiège > Chimie pharmaceutique
Segers, P.
D'Orio, Vincenzo ;  Université de Liège - ULiège > Département des sciences cliniques > Médecine d'urgence - bioch. et phys. hum. normales et path.
Language :
English
Title :
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
Publication date :
September 2004
Journal title :
Journal of Pharmacology and Experimental Therapeutics
ISSN :
0022-3565
eISSN :
1521-0103
Publisher :
Amer Soc Pharmacology Experimental Therapeutics, Bethesda, United States - Maryland
Volume :
310
Issue :
3
Pages :
964-972
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 23 December 2008

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