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Brief adrenomedullin inhalation leads to sustained reduction of pulmonary artery pressure

¹ Klinik für Kinder und Jugendliche und ² Pathologisches Institut, der Friedrich-Alexander-Universität, Erlangen-Nürnberg, Germany.

CORRESPONDENCE: M.A. Kandler, Klinik für Kinder und Jugendliche, Loschgestrasse 15, D-91054 Erlangen, Germany. Fax: 49 91318535867. E-mail: michael.kandler@web.de

Keywords: Acute respiratory distress syndrome, adrenomedullin, aerosol, endothelin-1, pulmonary hypertension

Received: February 12, 2003
Accepted May 28, 2004

Supported by a grant from the IZKF (center for interdisciplinary clinical research), University Erlangen-Nürnberg, German Ministry for Education and Research, No. 01 KS 0002, Project C11.

The effect of aerosolised adrenomedullin (ADM), a potent vasodilator peptide, on pulmonary artery pressure was studied for 24 h in a surfactant-depleted piglet model.

Animals received either aerosolised ADM (50 ng·kg^–1·min^–1, ADM, n=6), or aerosolised normal saline solution (control, n=6). Aerosol therapy was performed for a 2 h treatment period followed by a 22 h observation period. Ventilator settings were adapted to keep arterial oxygen tension and carbon dioxide arterial tension between 13.3–14.6 kPa and 4.9–5.7 kPa, respectively.

Aerosolised ADM reduced mean pulmonary artery pressure (MPAP) compared with the control group (end-point median 24 h after therapy start: MPAP –14.0 versus –8.0 mmHg; 23.5 h after therapy start). After therapy start, mean systemic arterial pressure (MAP) was not significantly different between the groups (end-point median: MAP ADM 70 (61/74) versus control 72 (54/81) mmHg). Endothelin-1, a potent pulmonary vasoconstrictor, is regulated by ADM via cAMP. Twenty two hours after inhalation of aerosolised ADM, endothelin-1 mRNA in lung tissue and endothelin-1 protein expression in pulmonary arteries was reduced compared with controls (median semi-quantitative immunhistochemical score: ADM 0.21, control 0.76).

Aerosolised adrenomedullin significantly reduced mean pulmonary artery pressure independently of arterial oxygen tension.

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