Inhaled endothelin A antagonist improves arterial oxygenation in experimental acute lung injury.
OBJECTIVE
To study the effects of an inhaled endothelin A (ET(A)) receptor antagonist on hemodynamics and pulmonary gas exchange in experimental acute lung injury (ALI).


METHODS
Prospective, randomized, and controlled study in a university laboratory.


METHODS
Sixteen pigs were ventilated in a volume controlled mode during general anesthesia. ALI was induced by surfactant depletion using repetitive lung lavages until the PaO2/FIO2 ratio was below 100 mmHg. The animals were then randomly assigned to receive either a nebulized ET(A) receptor antagonist (LU-135252, 3 mg/kg, inhaled over 1 h; LU group) or nebulization of saline (5-10 ml inhaled over 1 h) with no further intervention (controls).


RESULTS
Parameters of hemodynamics and gas exchange were measured for 6 h after induction of ALI. In the LU group intrapulmonary right-left shunting (QS/QT) decreased from 58 +/- 8% at the onset of ALI to 27 +/- 12% 3 h and 24 +/- 9% 6 h after ALI (p < 0.05); PaO2 increased from 55 +/- 12 to 257 +/- 148 mmHg 3 h and 270 +/- 136 mmHg 6 h after ALI. (p < 0.05), whereas in controls QS/QT and PaO2 did not improve over the 6 h after onset of ALI. In the LU group mean pulmonary artery pressure was stable for 6 h after ALI (26-29 mmHg), while in controls it increased from 28 +/- 2 to 41 +/- 2 mmHg (p < 0.05). Inhaled LU-135252 reduced cardiac output by 31 +/- 11% (p < 0.05) and increased systemic vascular resistance by 60 +/- 29 % (p < 0.05), while these parameters remained stable in controls.


CONCLUSIONS
In this porcine model of ALI the inhalation of an ET(A) receptor antagonist improved arterial oxygenation and maintained a stable pulmonary artery pressure without inducing systemic vasodilatation.
Kaisers
U
U
Department of Anesthesiology and Operative Intensive Care Medicine, Charité, Medizinische Fakultät, Humboldt-Universität, Berlin, Germany. udo.kaisers@charite.de
Busch
T
T
Wolf
S
S
Lohbrunner
H
H
Wilkens
K
K
Hocher
B
B
Boemke
W
W
D000280:Administration, Inhalation; D000818:Animals; D004195:Disease Models, Animal; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007231:Infant, Newborn; D010666:Phenylpropionates / Q000008:administration & dosage / Q000494:pharmacology*; D011446:Prospective Studies; D011659:Pulmonary Gas Exchange / Q000187:drug effects*; D011743:Pyrimidines / Q000008:administration & dosage / Q000494:pharmacology*; D012127:Respiratory Distress Syndrome, Newborn / Q000188:drug therapy; D018709:Statistics, Nonparametric; D013552:Swine
D010666:Phenylpropionates; D011743:Pyrimidines; C107831:darusentan