[en] We studied the effects on pulmonary hemodynamics of U-46619, a thromboxane A2 (TXA2) agonist, before and after administration of a novel TXA2 receptor antagonist and synthase inhibitor (BM-573). Six anesthetized pigs (Ago group) received 6 consecutive injections of U-46619 at 30-min interval and were compared with six anesthetized pigs (Anta group) which received an increasing dosage regimen of BM-573 10 min before each U-46619 injection. Consecutive changes in pulmonary hemodynamics, including characteristic resistance, vascular compliance, and peripheral vascular resistance, were continuously assessed during the experimental protocol using a four-element Windkessel model. At 2 mg/kg, BM-573 completely blocked pulmonary hypertensive effects of U-46619 but pulmonary vascular compliance still decreased. This residual effect can probably be explained by a persistent increase in the tonus of the pulmonary vascular wall smooth muscles sufficient to decrease vascular compliance but not vessel lumen diameter. Such molecule could be a promising therapeutic approach in TXA2 mediated pulmonary hypertension as it is the case in pulmonary embolism, hyperacute lung rejection and endotoxinic shock.
Disciplines :
Anesthesia & intensive care
Author, co-author :
Lambermont, Bernard ; Centre Hospitalier Universitaire de Liège - CHU > Frais communs médecine
Kolh, Philippe ; Département des sciences biomédicales et précliniques > Services généraux (Fac. de psycho. et des sc. de l'éducat.) > Biochimie et physiologie générales, humaines et pathologiques
Dogné, Jean-Michel ; Université de Liège - ULiège > Département de pharmacie > Département de pharmacie
Ghuysen, Alexandre ; Université de Liège - ULiège > Département des sciences de la santé publique > Réanimation - Urgence extrahospitalière
Tchana-Sato, Vincent ; Centre Hospitalier Universitaire de Liège - CHU > Chirurgie cardio-vasculaire
Morimont, Philippe ; Centre Hospitalier Universitaire de Liège - CHU > Frais communs médecine
Benoit, P.
Gérard, Paul ; Université de Liège - ULiège > Département de mathématique > Statistique (aspects expérimentaux)
Masereel, B.
Limet, Raymond ; Université de Liège - ULiège > Département des sciences cliniques > Chirurgie cardio-vasculaire et thoracique
D'Orio, Vincenzo ; Université de Liège - ULiège > Département des sciences cliniques > Médecine d'urgence - bioch. et phys. hum. normales et path.
Language :
English
Title :
Effects of U-46619 on Pulmonary Hemodynamics before and after Administration of Bm-573, a Novel Thromboxane A2 Inhibitor
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