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The role of endothelin-1 as a mediator of the pressure response after air embolism in blood perfused lungs

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Abstract

Objective: It is well known that lung embolism is associated with an increase in pulmonary vascular resistance. Since the mechanisms of pulmonary vascular reactions during embolism are still unclear, the aim of this study was to investigate the potential involvement of endothelin-1 (ET-1) and thromboxane A2 (TXA2) as mediators of the pulmonary artery pressure (PAP) increase after embolism using the selective ETA receptor antagonist LU135252 [1], the ETB receptor antagonist BQ788 [2], and the cy-clooxygenase inhibitor diclofenac.

Design: Prospective experimental study in rabbits.

Setting: Experimental laboratory in a university teaching hospital.

Subjects: 36 adult rabbits of either sex.

Interventions: The experiments were performed in 36 isolated and ventilated rabbit lungs which were perfused with a buffer solution containing 10 % of autologous blood. Embolism was induced by the injection of 0.75 ml air into the pulmonary artery.

Measurements and results: PAP and lung weight, reflecting edema formation, were continuously recorded. Perfusate samples were drawn intermittently to determine TXA2 and ET-1 concentrations. Air injection resulted in an immediate increase in PAP up to 22.8 ± 1.4 mm Hg at 2.5 min (control, n=6), which was parallelled by an enhanced generation of TXA2. No relevant edema formation occurred during the observation period. Pretreatment with the ETA receptor antagonist LU135 252 significantly reduced the pressure reaction after air embolism (p<0.001) whereas the ETB receptor antagonist BQ788 (n=6) was without marked effects. The administration of diclofenac (n=6) did not alter the PAP increase 2.5 min after embolism, but significantly reduced the pressure reaction during the further observation period (p<0.001). The application of LU135 252 and diclofenac together (n=6) also significantly reduced the PAP increase from 2.5 min during the total observation period (p < 0.001).

Conclusions: The acute pressure reaction after air embolism is mainly mediated via ET-1 by an ETA receptor related mechanism. TXA2 seems to maintain this reaction for a longer time.

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Authors and Affiliations

  1. Institute of Anesthesiology and Operative Intensive Care Medicine, Faculty of Clinical Medicine Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer, D-68135, Mannheim, Germany

    J. Schmeck, T. Koch, A. Heller & K. van Ackern

  2. Division of Clinical Pathophysiology and Experimental Medicine, Department of Internal Medicine, University of Giessen, Germany

    B. Patt & H. Neuhof

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  1. J. Schmeck
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  2. T. Koch
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Schmeck, J., Koch, T., Heller, A. et al. The role of endothelin-1 as a mediator of the pressure response after air embolism in blood perfused lungs. Intensive Care Med 24, 605–611 (1998). https://doi.org/10.1007/s001340050622

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  • DOI: https://doi.org/10.1007/s001340050622

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