To investigate the hypothesis that the inhaled ETA receptor antagonist LU-135252 acts as selective pulmonary vasodilator, we compared inhaled LU-135252 and inhaled nitric oxide (iNO) in an experimental model of acute lung injury (ALI), in a prospective, randomized, controlled animal study. A total of 30 anaesthetized, tracheotomized and mechanically ventilated pigs underwent induction of ALI by repeated saline washout of surfactant. The animals were then randomly assigned to receive the nebulized ETA receptor antagonist LU-135252 (0.3mg·kg-1, inhaled over 20min; ETA-A group; n = 10), inhaled NO (30p.p.m. continuously; iNO group; n = 10) or nebulized saline buffer (5ml inhaled over 20min; control group; n = 10). Measurements of pulmonary gas exchange and haemodynamics were performed hourly over a 4h period after induction of ALI. In the ETA-A group, the arterial oxygen tension (Pao2) increased from 58±3 to 377±39mmHg at 4h after intervention, while the intrapulmonary shunt (QS/QT) decreased from 53±4% to 18±2% (P<0.01 compared with controls). In the iNO group, PaO2 increased from 62±4 to 224±48mmHg, and QS/QT decreased from 47±2% to 27±5%, at 4h after induction of ALI (P<0.05 compared with controls). In the ETA-A and iNO groups, the increase in mean pulmonary artery pressure was significantly attenuated compared with controls (ETA-A group, 14±4%; iNO group, 6±4%; values at 4h; P<0.01compared with controls). In contrast, there were no significant differences in changes of mean arterial pressure and cardiac output between groups. Thus, in this experimental model of ALI, both inhaled LU-135252 and iNO significantly improved gas exchange and prevented an increase in mean pulmonary artery pressure, without significant systemic effects, when compared with controls. Our results indicate the occurrence of selective pulmonary vasodilation in both treatment groups.
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September 2002
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Conference Article|
September 01 2002
The inhaled ETA receptor antagonist LU-135252 acts as a selective pulmonary vasodilator
Maria DEJA;
Maria DEJA
1Klinik für Anaesthesiologie und Operative Intensivmedizin Charité, Campus Virchow-Klinikum, Medizinische Fakultät der Humboldt-Universitaet, Augustenburger Platz 1, D-13353 Berlin, Germany
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Steffen WOLF;
Steffen WOLF
1Klinik für Anaesthesiologie und Operative Intensivmedizin Charité, Campus Virchow-Klinikum, Medizinische Fakultät der Humboldt-Universitaet, Augustenburger Platz 1, D-13353 Berlin, Germany
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Thilo BUSCH;
Thilo BUSCH
1Klinik für Anaesthesiologie und Operative Intensivmedizin Charité, Campus Virchow-Klinikum, Medizinische Fakultät der Humboldt-Universitaet, Augustenburger Platz 1, D-13353 Berlin, Germany
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Bodil PETERSEN;
Bodil PETERSEN
1Klinik für Anaesthesiologie und Operative Intensivmedizin Charité, Campus Virchow-Klinikum, Medizinische Fakultät der Humboldt-Universitaet, Augustenburger Platz 1, D-13353 Berlin, Germany
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Ursel JAGHZIES;
Ursel JAGHZIES
1Klinik für Anaesthesiologie und Operative Intensivmedizin Charité, Campus Virchow-Klinikum, Medizinische Fakultät der Humboldt-Universitaet, Augustenburger Platz 1, D-13353 Berlin, Germany
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Willehad BOEMKE;
Willehad BOEMKE
1Klinik für Anaesthesiologie und Operative Intensivmedizin Charité, Campus Virchow-Klinikum, Medizinische Fakultät der Humboldt-Universitaet, Augustenburger Platz 1, D-13353 Berlin, Germany
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Udo KAISERS
1Klinik für Anaesthesiologie und Operative Intensivmedizin Charité, Campus Virchow-Klinikum, Medizinische Fakultät der Humboldt-Universitaet, Augustenburger Platz 1, D-13353 Berlin, Germany
Dr Udo Kaisers (e-mail [email protected]).
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Publisher: Portland Press Ltd
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© 2002 The Biochemical Society and the Medical Research Society
2002
Clin Sci (Lond) (2002) 103 (s2002): 21S–24S.
Citation
Maria DEJA, Steffen WOLF, Thilo BUSCH, Bodil PETERSEN, Ursel JAGHZIES, Willehad BOEMKE, Udo KAISERS; The inhaled ETA receptor antagonist LU-135252 acts as a selective pulmonary vasodilator. Clin Sci (Lond) 1 September 2002; 103 (s2002): 21S–24S. doi: https://doi.org/10.1042/CS103S021S
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