BMC Pulmonary Medicine (Jul 2009)

Tolerability of inhaled N-chlorotaurine in the pig model

  • Scholl-Bürgi Sabine,
  • Wemhöner Andreas,
  • Giese Thomas,
  • Steiner Hans-Jörg,
  • Walther Christoph,
  • Hauer Maria,
  • Pilch Michael,
  • Reinstadler Hannes,
  • Prossliner Harald,
  • Barnickel Linn,
  • Pinna Anna,
  • Treml Benedikt,
  • Geiger Ralf,
  • Gottardi Waldemar,
  • Arnitz Roland,
  • Sergi Consolato,
  • Nagl Markus,
  • Löckinger Alexander

DOI
https://doi.org/10.1186/1471-2466-9-33
Journal volume & issue
Vol. 9, no. 1
p. 33

Abstract

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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.