Postconditioning with a volatile anesthetic in alveolar epithelial cells in vitro

¹ Institute of Anesthesiology, University of Zurich, Zurich, Switzerland
² Institute of Physiology and Zurich Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland
³ Dept of Anesthesiology, Orthopedic University Clinic Zurich Balgrist, Zurich, Switzerland
⁴ Institute of Anesthesiology, University of Zurich, Zurich, Switzerland; and Institute of Physiology and Zurich Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland

^* To whom correspondence should be addressed. E-mail: Beatrice_Beck.Schimmer{at}access.uzh.ch.

	Abstract

Acute lung injury (ALI) is a common complication in critically ill patients. We examined possible immunomodulating effects of the volatile anesthetic sevoflurane on lipopolysaccharide (LPS)-stimulated alveolar epithelial cells (AEC) in vitro.

Sevoflurane was applied after the onset of injury, simulating a "postconditioning" scenario. Rat AEC were stimulated with LPS for 2 h, followed by a 4 h co-exposure to a CO₂/air mixture with sevoflurane 2.2 Vol %, control cells were exposed to the CO₂/air mixture only. Cytokine-induced neutrophil chemoattractant-1 (CINC-1), monocyte chemoattractant protein-1 (MCP-1), intercellular adhesion molecule-1 (ICAM-1), as well as the potential protective mediators inducible nitric oxide synthase 2 (iNOS2), and heat shock protein-32 (HSP-32) were analyzed. Additionally, functional assays (chemotaxis, adherence and cytotoxicity assay) were performed.

A significant reduction of inflammatory mediators in LPS-stimulated, sevoflurane-exposed AEC was found, leading to reduced chemotaxis, neutrophil adherence, and neutrophil-induced AEC killing. While iNOS2 was increased in the sevoflurane group, blocking experiments with iNOS2 inhibitor did not affect sevoflurane-induced decrease of inflammatory mediators and AEC killing. Interestingly, sevoflurane treatment also resulted in an enhanced expression of HSP-32.

The data presented in this study provide strong evidence that anesthetic postconditioning with sevoflurane mediates cytoprotection in the respiratory compartment in an in vitro model of ALI.