BENEFICIAL ACTIONS OF THROMBOXANE RECEPTOR ANTAGONISM IN HEMORRHAGIC-SHOCK

  • 1 January 1986
    • journal article
    • research article
    • Vol. 20  (1) , 1-11
Abstract
The new specific thromboxane receptor antagonist, BM-13505, was infused intravenously (1 mg/kg bolus and 1 mg/kg hr continuous infusion) to determine its effect in a feline model of hemorrhagic shock. Hemorrhaged cats treated with BM-13505 maintained postreinfusion mean arterial blood pressure and superior mesenteric artery flow at significantly higher values compared to cats receiving only the vehicle. BM-13505 was also found to attenuate the increase in plasma cathepsin D activity in hemorrhaged cats as well as to curtail plasma proteolysis to values not significantly different from sham shock animals at the end of the post-reinfusion period. Furthermore, the plasma activity of a myocardial depressant factor (MDF) was significantly lower in BM-13505-treated shocked cats than in the vehicle group (37 .+-. 4 vs 71 .+-. 7 U/ml, P < .01). Additionally, BM-13505 was shown to antagonize thromboxane-induced vasoconstriction in isolated perfused cat coronary arteries and to exert an anti-aggregatory effect in platelet-rich cat plasma induced by the endoperoxide analog, U-46619. However, BM-13505 failed to show a direct antiproteolytic effect in cat pancreatic homogenates. Thus, the beneficial effects of BM-13505 in hemorrhagic shock are likely due to both its prevention of thromboxane-induced vasoconstriction and its ability to attenuate thromboxane-induced platelet aggregation. Our results further substantiate the role of thromboxane A2 as a mediator of hemorrhagic shock and suggest that antagonism of thromboxane receptors may be useful in the treatment of hemorrhagic shock.