Study objectives: To evaluate the effects of
nonselective endothelin (ET)-receptor antagonism on the hemodynamic
changes and serum thromboxane (TX)-A2 levels after a
massive pulmonary air embolism (PAE) in dogs.
Interventions: Anesthetized mongrel dogs
(ET-receptor antagonist group; n = 6) received a bolus injection of 1
mg of the nonselective ET-A/ET-B-receptor antagonist PD 145065 (Sigma
Chemical; St. Louis, MO), and dogs in the control group
(n = 6) received saline solution. Hemodynamic data were recorded 5
min after the administration of antagonist or saline solution.
Subsequently, 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. Arterial blood samples were drawn at baseline and 15 min
after PAE for the determination of plasma TX-A2, measured
by enzyme-linked immunosorbent assay as TX-B2 (the stable
metabolite of TX-A2).
Results: PD 145065
alone produced no hemodynamic effects. However, dogs pretreated 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%,
respectively). The mean arterial pressure (MAP), cardiac index (CI),
and plasma TX-B2 levels were unaltered after PAE in the
presence of ET-receptor antagonist, whereas CI and MAP decreased 5 to
10 min after PAE, and TX-B2 concentrations increased 15 min
after PAE in control dogs (p < 0.05 in all cases).
Conclusions: Nonselective antagonism of ET receptors
attenuates the pulmonary hypertension and blunts the TX-A2
release caused by massive PAE in dogs.