The Immune Response to One-Lung Ventilation : Clinical and Experimental Studies

• Main Author: Schilling, Thomas
• Format: Doctoral Thesis
• Language: English
• Published: Uppsala universitet, Klinisk fysiologi 2009
• Subjects: One-lung ventilation; open thoracic surgery; ventilation-induced lung injury; alveolar immune response; bronchoalveolar lavage; propofol; desflurane; cytokines; animal model; mRNA; RT-PCR; Medical laboratory science; Medicinsk laboratorievetenskap
• Online Access: http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-108851; http://nbn-resolving.de/urn:isbn:978-91-554-7651-9

One-lung ventilation (OLV) as an established procedure during thoracic surgery may be injurious in terms of increased mechanical stress characterised by alveolar cell stretch and overdistension, increased cyclic tidal recruitment of alveolar units, compression of alveolar vessels and increased pulmonary vascular resistance. This may result in ventilation-induced lung injury with pro-inflammatory cytokine production, leukocyte recruitment and neutrophil-dependent tissue destruction. Despite the consequences of delivering the whole tidal volume (VT) to only a single lung, relatively high VT are used during OLV to maintain arterial oxygenation and carbon dioxide elimination. However, this may increase mechanical stress in the dependent lung and may aggravate alveolar injury. There is a lack of data on the alveolar immune consequences of OLV. Therefore, the present studies investigate the epithelial damage and pro-inflammatory response induced by mechanical ventilation and OLV. OLV induced pulmonary injury, but alveolar damage in the ventilated lung decreased by reduction of the tidal volume in patients scheduled for thoracic surgery (study I). The use of the volatile anaesthetic desflurane in OLV patients attenuated the OLV-induced alveolar immune response (study II). Furthermore, an experimental model of thoracic surgery was established to investigate the systemic and pulmonary consequences of OLV and thoracic surgery in comparison with the effects of conventional two-lung ventilation and spontaneous breathing. The experimental data indicate that beside the pulmonary immune response volatile anaesthetics have also modulated the plasma concentrations of cytokines during and after OLV (study III). In contrast, OLV and thoracic surgery increased the expression of pro-inflammatory mRNA in BAL cells and lung tissue samples. General anaesthesia did not affect this response (study 4). The results of the present studies indicate that OLV and thoracic surgery may be injurious to the lung tissue to a similar degree. The recruitment and activation of alveolar granulocytes characterise the alveolar damage. The administration of different anaesthetics modulates the activation of alveolar cells, specified by decreased inflammatory mediator release in subjects that receive desflurane anaesthesia, which does not affect the expression of cytokine mRNA in alveolar cells and lung tissue samples.