Nonselective endothelin-receptor antagonism attenuates hemodynamic changes after massive pulmonary air embolism in dogs.
OBJECTIVE
To evaluate the effects of nonselective endothelin (ET)-receptor antagonism on the hemodynamic changes and serum thromboxane (TX)-A(2) levels after a massive pulmonary air embolism (PAE) in dogs.


METHODS
Prospective trial.


METHODS
University laboratory.


METHODS
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-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 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-B(2) 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-B(2) 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-A(2) release caused by massive PAE in dogs.
Tanus-Santos
J E
JE
Department of Pharmacology, State University of Campinas, Campinas, São Paulo, Brazil.
Gordo
W M
WM
Udelsmann
A
A
Cittadino
M H
MH
Moreno
H
H
D000818:Animals; D004285:Dogs; D004618:Embolism, Air / Q000503:physiopathology*; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000502:physiology; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology*; D011446:Prospective Studies; D011655:Pulmonary Embolism / Q000503:physiopathology*; D013931:Thromboxanes / Q000097:blood*
D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D009842:Oligopeptides; D013931:Thromboxanes; C082887:PD 145065