[en] Thromboxane A2 is considered to be partially responsible for the increase in pulmonary vascular resistance observed after endotoxin administration and to participate in proinflammatory reactions. The effects of a novel dual TXA2 synthase inhibitor and TXA2 receptor antagonist (BM-573) on pulmonary hemodynamics were investigated in endotoxic shock. 30 mins before the start of a 0.5 mg/kg endotoxin infusion, 6 pigs (Endo group) received a placebo infusion and 6 other pigs (Anta group) received a BM-573 infusion. In Endo group, pulmonary artery pressure increased from 25 +/- 1.8 (T0) to 42 +/- 2.3 mmHg (T60) (p < 0.05) after endotoxin infusion while, in Anta group, it increased from 23 +/- 1.6 (T0) to 25 +/- 1.5 mmHg (T60). This difference is due to a reduction in pulmonary vascular resistance in Anta group while pulmonary arterial compliance changes in Endo group remained comparable with the evolution in Anta group. In Endo group, PaO2 decreased from 131 +/- 21 (T0) to 74 +/- 12 mmHg (T300) (p < 0.05), while in Anta group, PaO2 was 241 +/- 31 mmHg at the end of the experimental period (T300). These results demonstrate that TXA2 plays a major role in pulmonary vascular changes during endotoxin insult. Concomitant inhibition of TXA2 synthesis and of TXA2 receptors by BM-573 inhibited the pulmonary vasopressive response during the early phase of endotoxin shock as well as the deterioration in arterial oxygenation.
Disciplines :
General & internal medicine
Author, co-author :
Lambermont, Bernard ; Centre Hospitalier Universitaire de Liège - CHU > Frais communs médecine
Ghuysen, Alexandre ; Université de Liège - ULiège > Département des sciences de la santé publique > Réanimation - Urgence extrahospitalière
Dogné, Jean-Michel ; Université de Liège - ULiège > Département de pharmacie > Département de pharmacie
Kolh, Philippe ; Université de Liège - ULiège > Services généraux (Fac. de psycho. et des sc. de l'éducat.) > Relations académiques et scientifiques (Psycho et sc.éduc.) - Relations académiques et scientifiques (Sciences)
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.
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 Bm-573, a Novel Thromboxane A2 Inhibitor, on Pulmonary Hemodynamics in Endotoxic Shock
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