Tolerability of N-chlorotaurine, a new endogenous antiseptic, in the bronchopulmonary system
Abstract number: P967
Pinna A., Geiger R., Treml B., Barnickel L., Walther C., Scholl-Bürgi S., Gottardi W., Arnitz R., Sergi C., Löckinger A., Nagl M.
Objective: N-chlorotaurine, an important representative of the long-lived oxidants produced by human leukocytes, can be applied in human medicine as an endogenous antiseptic. This study was designed to evaluate the tolerability of inhalative N-chlorotaurine (NCT) in the pig model.
Methods: Anesthetised pigs inhaled test solutions of 1% NCT (n = 7), 5% NCT (n = 6), or 1% NCT plus 1% ammonium chloride (n = 6), and 0.9% saline solution as a control (n = 7), respectively. Applications were performed every hour within four hours, i.e. 4 inhalations in total, with 5 ml each. Lung function, blood oxygenation, and circulation were monitored. Pharmacokinetics were investigated by oxidation capacity in bronchial fluid and by determination of taurine and chloride in serum. One hour after the last dosing the animals were euthanised, and lung samples for histology were removed.
Results: Arterial pressure of oxygen (PaO2) decreased significantly over the observation period of 4 hours in all animals. Compared to saline, only 1% NCT + 1% NH4Cl led to significantly lower PaO2 values at the 4 hours measurement (62 mmHg ± 9.6 vs. 76 mmHg ± 9.2, p = 0.014). The corresponding increase in alveolo-arterial difference of oxygen partial pressure (AaDO2) was significantly higher only in the 1% NCT + 1% NH4Cl than in the control group (P < 0.01), too. Pulmonary artery pressure increased about 9.7 mmHg by 5% NCT, about 7.8 mmHg by 1% NCT + 1% NH4Cl (P < 0.05 versus control), about 4.3 mmHg by 1% NCT (P > 0.05 versus control), and about 6.7 mmHg by saline.
Histological investigations revealed inflammatory reactions, districts with atelectasia, districts with emphysema, and districts with fragmentation of fibers in both the test groups and in the saline group with no statistical difference.
There was no systemic resorption of NCT detectable. Local inactivation of NCT below detectable levels took place within 30 min. The concentration of NCT tolerated by A549 lung epithelial cells in vitro was 0.250.5 mM, which was similar to that known from other body cells and 25-fold higher than that of chloramine T.
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 statistically significant impact on blood oxygenation, which would require adjustment of dose. These results are in accordance with previous clinical studies in man and animals.
|Session name:||18th European Congress of Clinical Microbiology and Infectious Diseases|
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