3, Table 1). Ventilation at both very high and low volumes can lead to VILI (Frank et al., 2002). When connective tissue and parenchymal cells are exposed to high mechanical load, an adaptation process to tensile stress can start. Once extracellular matrix provides pulmonary structural mechanical support, it can be altered in response to mechanical

stress (Parker et al., 1997). Collagen represents one of these structural proteins and the stimulus to its synthesis can be pinpointed by the expression of PCIII mRNA expression (Raghu et al., Idelalisib solubility dmso 1985). Thus, we used PCIII mRNA as a marker of tissue damage since type-III procollagen is one of the first molecules to be synthesized during the lung fibrotic process (Raghu et al., 1985). Indeed, PCIII mRNA was significantly higher in V10P2 group at the end of OLV (Fig. 4). The early response of PCIII mRNA is in line with previous two-lung ventilation studies (Garcia et al., 2004, Farias et al., 2005 and De Carvalho et al., 2007). According to De Carvalho et al. (2007), overdistension due to mechanical ventilation with high VT leads to an early response of the extracellular matrix, resulting

in a significantly increase of PCIII mRNA expression. Interestingly, the extra pressure added to the respiratory system by the 3 cm H2O difference in PEEP (from V5P2 to V5P5) increased lung volume by 0.62 ml at the beginning of OLV and by 0.35 ml Tyrosine Kinase Inhibitor Library at the end of OLV (calculated considering Csp at each instance, as depicted in Fig. 2, and EELV to calculate compliance, and, then delta volume), whereas the change in lung volume due

to the extra gas volume added to the system from V5P2 to V10P2 was about 1 ml (= 5 ml/kg BW × 200 g BW). To our knowledge, no study has examined procollagen type-III expression during OLV. Under HSP90 the translational point of view, it should be stressed that in the present study both hemithoraces were open to the atmosphere, since the animals were in the supine position, as sometimes used in median sternotomy (Asaph et al., 2000). In this context, our results suggest that the use of high or low tidal volume without PEEP should be avoided during OLV applied in the face of median sternotomy, and perhaps under other sorts of thoracotomy as well. The authors acknowledge limitations in the current study. First, we used only one ventilation mode (VCV). It would be interesting to compare the present results with those in PCV ventilation mode. Second, hemodynamic parameters were not controlled. PEEP may interfere with vascular pressure and cardiac output. Third, OLV lasted just 1 h and, thus, we cannot exclude the possibility that longer ventilation time with low tidal volume (5 ml/kg), independently of PEEP level, could increase PCIII mRNA expression. Fourth, PCIII mRNA represents an indicator of PCIII synthesis, which may not happen after all.