Nonselective endothelin-receptor antagonism attenuates hemodynamic changesafter massive pulmonary air embolism in dogs

Study objectives: To evaluate the effects of nonselective endothelin (ET)-r eceptor antagonism on the hemodynamic changes and serum thromboxane (TX)-A( 2) levels after a massive pulmonary air embolism (PAE) in dogs. Design: Prospective trial. Setting: University laboratory. Interventions: Anesthetized mongrel dogs (ET-receptor antagonist group; n = 6) received a bolus injection of 1 mg of the nonselective ET-A/ET-B-recept or antagonist PD 145065 (Sigma Chemical; St. Louis, MO), and dogs in the co ntrol group (n = 6) received saline solution. Hemodynamic data were recorde d 5 min after the administration of antagonist or saline solution. Subseque ntly, each dog received 2.5-mL air/kg via the right femoral vein (the PAE), and the hemodynamic data were recorded for up to 60 min thereafter. Arteri al blood samples were drawn at baseline and 15 min after PAE for the determ ination of plasma TX-A(2), measured by enzyme-linked immunosorbent assay as TX-B-2 (the stable metabolite of TX-A(2)). Results: PD 145065 alone produced no hemodynamic effects. However, dogs pre treated with PD 145065 had significantly lower increases in mean pulmonary arterial pressure and in pulmonary vascular resistance after the PAE (116% and 165%, respectively) compared to the control dogs (187% and 367%, respec tively). The mean arterial pressure (MAP), cardiac index (CI), and plasma T X-B-2 levels were unaltered after PAE in the presence of ET-receptor antago nist, whereas CI and MAP decreased 5 to 10 min after PAE, and TX-B-2 concen trations increased 15 min after PAE in control dogs (p < 0.05 in all cases) . Conclusions: Nonselective antagonism of ET receptors attenuates the pulmona ry hypertension and blunts the TX-A(2) release caused by massive PAE in dog s.