Abstract
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 ml inhaled over 1 h) with no further intervention (controls).
Measurements 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 (Q̇S/Q̇T) 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 Q̇S/Q̇T 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.
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An erratum to this article is available at http://dx.doi.org/10.1007/s001340000739.
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Kaisers, U., Busch, T., Wolf, S. et al. Inhaled endothelin A antagonist improves arterial oxygenation in experimental acute lung injury. Intensive Care Med 26, 1334–1342 (2000). https://doi.org/10.1007/s001340000608
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DOI: https://doi.org/10.1007/s001340000608