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BMC Pulmonary Medicine

, 9:33

First Online: 14 July 2009Received: 03 December 2008Accepted: 14 July 2009

Abstract

BackgroundN-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.

MethodsAnesthetized 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.

ResultsArterial 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.

ConclusionThe 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.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2466-9-33 contains supplementary material, which is available to authorized users.

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Autor: Ralf Geiger - Benedikt Treml - Anna Pinna - Linn Barnickel - Harald Prossliner - Hannes Reinstadler - Michael Pilch - Maria

Fuente: https://link.springer.com/



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