Aerosol-PFC

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

The applications mission is treatment of pulmonary diseases by aerososolized perfluorocarbon(PFC). This new technology of PFC aerosolization via an introducible jet-nebulizer (Aer-Probe, Trudell) has been demonstrated in several animal studies (Kandler, von der Hardt). Aerosol way of PFC application offers a safe and easy to handle procedure for perfluorocarbon assisted ventilation. Patients with ARDS and neonatal respiratory distress syndrome show sustained improvement in gas exchange and lung mechanics. Ventilator associated lung injury is attenuated by the applied perfluorocarbon, diminishing inflammatory induction of chronic lung disease.

Technology is dedicated to perfluorocabons relatively independent from the molecular structure. It offers the chance to register an appropriate PFC for use as respiratory drug.

Recent invetigations showed after induction of lung injury by repeated saline lung lavage due to surfactant depletion in neonatal piglets, the new ventilatory strategy with aerosolized perfluorocarbon led to a reduction of the initial pulmonary inflammatory reaction and an improvement of gas exchange.

Gene expression of IL-1ß, IL-6, IL-8 and TGF-ß1 in pulmonary tissue was significantly lower in surfactant depleted neonatal piglets with severe respiratory distress syndrome receiving aerosolized perfluorocarbon (Aerosol-PFC) than in the control group ventilated with intermittent mandatory ventilation (von der Hardt, Kandler). In this surfactant piglet model, mRNA expression of inflammation mediated adhesion molecules, such as E-Selectin, P-Selectin and ICAM-1 was effectively diminished by using aerosolized perfluorocarbon (Schoof, von der Hardt). Relative neutrophil infiltration in lung tissue was significantly reduced after treatment with aerosolized perfluorocarbon. Proinflammatory cytokines and intercellular adhesion molecules in porcine lung tissue participating in acute pulmonary inflammatory response were detected and could be modulated by a new protective respiratory support with aerosolized perfluorocarbon.

References

  • Kandler, von der Hardt: Am J Respir Crit Care Med. 2001 Jul 1;164(1):31-5 Persistent improvement of gas exchange and lung mechanics by aerosolized perfluorocarbon. (Kandler MA, von der Hardt K, Schoof E, Dotsch J, Rascher W.) Klinik fur Kinder und Jugendliche der Friedrich-Alexander-Universitat, Erlangen-Nurnberg, Germany.
  • von der Hardt, Kandler: Pediatr Res. 2002 Feb;51(2):177-82. Aerosolized perfluorocarbon suppresses early pulmonary inflammatory response in a surfactant-depleted piglet model. (von der Hardt K, Schoof E, Kandler MA, Dotsch J, Rascher W.) Klinik fur Kinder und Jugendliche der Friedrich-Alexander-Universitat Erlangen-Nurnberg, D-91054 Erlangen, Germany.
  • Schoof, von der Hardt: Eur J Pharmacol. 2002 Dec 20;457(2-3):195-200. Aerosolized perfluorocarbon reduces adhesion molecule gene expression and neutrophil sequestration in acute respiratory distress. (Schoof E, von der Hardt K, Kandler MA, Abendroth F, Papadopoulos T, Rascher W, Dotsch J.) Klinik mit Poliklinik fur Kinder und Jugendliche, Pathologisch-Anatomisches Institut der Friedrich-Alexander-Universitat Erlangen-Nurnberg, Loschgestrasse 15, D-91054 Erlangen, Germany.



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