Inhaled endothelin A antagonist improves arterial oxygenation in experimental acute lung injury

Objectives: To study the effects of an inhaled endothelin A (ETA) receptor antagonist on hemodynamics and pulmonary gas exchange in experimental acute lung injury (ALI). Design and setting: Prospective, randomized, and controlled study in a university laboratory. Participants and interventions: 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 ETA receptor antagonist (LU-135252, 3 mg/kg, inhaled over 1 h; LU group) or nebulization of saline (5-10 mi inhaled over 1 h) with no further intervention (controls). Measurement and results: Parameters of hemodynamics and gas exchange were measured for 6 h after induction of ALI. In the LU group intrapulmonary right-left shunting (Q(S)/Q(T)) 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 Q(S)/Q(T) 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. Conclusion: In this porcine model of ALI the inhalation of an ETA receptor antagonist improved arterial oxygenation and maintained a stable pulmonary artery pressure without inducing systemic vasodilatation.