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Open Access Research article

Tolerability of inhaled N-chlorotaurine in the pig model

Ralf Geiger12, Benedikt Treml3, Anna Pinna4, Linn Barnickel5, Harald Prossliner3, Hannes Reinstadler3, Michael Pilch3, Maria Hauer3, Christoph Walther4, Hans-Jörg Steiner5, Thomas Giese6, Andreas Wemhöner7, Sabine Scholl-Bürgi12, Waldemar Gottardi4, Roland Arnitz4, Consolato Sergi5, Markus Nagl4* and Alexander Löckinger3

Author Affiliations

1 Department of Pediatrics, Division of Cardiology, Pulmology, Allergology and Cystic Fibrosis, Innsbruck Medical University, Innsbruck, Austria

2 Division of Neonatology, Neuropediatrics and Inborn errors of metabolism, Innsbruck Medical University, Innsbruck, Austria

3 Department of Anaesthesiology and Critical Care Medicine, Innsbruck Medical University, Innsbruck, Austria

4 Department of Hygiene, Microbiology and Social Medicine, Division of Hygiene and Medical Microbiology, Innsbruck Medical University, Innsbruck, Austria

5 Institute of Pathology, Innsbruck Medical University, Innsbruck, Austria

6 Department of Immunology, University of Heidelberg, Heidelberg, Germany

7 Technical University Dresden, University Hospital Dresden, Department for Pediatric Intensive Care and Neonatology, Dresden, Germany

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BMC Pulmonary Medicine 2009, 9:33  doi:10.1186/1471-2466-9-33

Published: 14 July 2009

Abstract

Background

N-chlorotaurine, a long-lived oxidant produced by human leukocytes, can be applied in human medicine as an endogenous antiseptic. Its antimicrobial activity can be enhanced by ammonium chloride. This study was designed to evaluate the tolerability of inhaled N-chlorotaurine (NCT) in the pig model.

Methods

Anesthetized pigs inhaled test solutions of 1% (55 mM) NCT (n = 7), 5% NCT (n = 6), or 1% NCT plus 1% ammonium chloride (NH4Cl) (n = 6), and 0.9% saline solution as a control (n = 7), respectively. Applications with 5 ml each were performed hourly within four hours. Lung function, haemodynamics, and pharmacokinetics were monitored. Bronchial lavage samples for captive bubble surfactometry and lung samples for histology and electron microscopy were removed.

Results

Arterial pressure of oxygen (PaO2) decreased significantly over the observation period of 4 hours in all animals. Compared to saline, 1% NCT + 1% NH4Cl led to significantly lower PaO2 values at the endpoint after 4 hours (62 ± 9.6 mmHg vs. 76 ± 9.2 mmHg, p = 0.014) with a corresponding increase in alveolo-arterial difference of oxygen partial pressure (AaDO2) (p = 0.004). Interestingly, AaDO2 was lowest with 1% NCT, even lower than with saline (p = 0.016). The increase of pulmonary artery pressure (PAP) over the observation period was smallest with 1% NCT without difference to controls (p = 0.91), and higher with 5% NCT (p = 0.02), and NCT + NH4Cl (p = 0.05).

Histological and ultrastructural investigations revealed no differences between the test and control groups. The surfactant function remained intact. There was no systemic resorption of NCT detectable, and its local inactivation took place within 30 min. The concentration of NCT tolerated by A549 lung epithelial cells in vitro was similar to that known from other body cells (0.25–0.5 mM).

Conclusion

The endogenous antiseptic NCT was well tolerated at a concentration of 1% upon inhalation in the pig model. Addition of ammonium chloride in high concentration provokes a statistically significant impact on blood oxygenation.