ONLINE DATA SUPPLEMENT
Discussion
Interestingly, the microscopic findings showed an increased inflammatory infiltrate in the lung parenchyma in all ventilated groups. Our results are in line with the studies of Conrad et al. [1], Uhlig [2] and Wolthuis et al. [3], who have found that even a careful ventilation strategy can lead to an inflammatory response and be potentially injurious to the lungs. However, it should be noted that the dangerous effects of MV were more evident in the HP group, followed by the HV group. The high peak inspiratory flow observed during pressure controlled ventilation was associated with more pronounced lung damage when compared to a low flow of volume-controlled ventilation with the same tidal volume, which can be explained by the increased shear stress during inspiration [4]. Additionally, we found the highest blood lactate levels in the HV and HP groups after the MV protocol. Increased lactate production has been described as a systemic effect of VILI and may reflect tissue hypoxia [5]. We inferred that increase in lactate came possibly from a whole body response to changes in hemodynamic in response to a possible decrease in cardiac output mediated by the increase in intrathoracic pressure imposed by high pressure ventilation.
References
1. Conrad SA, Zhang S, Arnold TC, Scott K, Carden DL (2005) Protective effects of low respiratory frequency in experimental ventilator-associated lung injury. Crit Care Med 33(4):835-840. doi: 10.1097/01.CCM.0000159532.56865.8A
2. Uhlig S (2002) Ventilation-induced lung injury and mechanotransduction: stretching it too far? Am J Physiol Lung Cell Mol Physiol 282:L892-L896. doi:10.1152/ajplung.00124.2001
3. Wolthuis EK, Vlaar AP, Choi G, Roelofs JJ, Juffermans NP, Schultz MJ (2009) Mechanical ventilation using non-injurious ventilation settings causes lung injury in the absence of pre-existing lung injury in healthy mice. Crit Care 13(1):R1. doi:10.1186/cc7688
4. Maeda Y, Fujino Y, Uchiyama A, Matsuura N, Mashimo T, Nishimura M (2004) Effects of peak inspiratory flow on development of ventilator-induced lung injury in rabbits. Anesthesiology 101(3):722-728
5. Slutsky AS, Tremblay LN (1998) Multiple System Organ Failure. Is Mechanical Ventilation a Contributing Factor? Am J Respir Crit Care Med 157:1721–1725
Additional figures
Fig. 1 Macroscopic analysis of ventilated rabbit lungs
The lungs of the control and the Low Volume groups were macroscopically identical (A and B) and appeared completely normal with no hemorrhage, atelectasis, or areas of consolidation. Lungs treated with high volume ventilation (C) showed spotty areas of hemorrhage and localized areas of atelectasis but no regions of obvious consolidation. Lungs treated with high pressure ventilation (D) at necropsy appeared cherry red with large areas of hemorrhagic consolidation. Lung inflation was maintained by providing 20 cm H2O of continuous positive airway pressure.
Fig. 2 Polymorphonuclear infiltrate
Representative histology of rabbit lung parenchyma in the control (A), Low Volume (B), High Volume (C) and High Pressure (D) groups (H&E 400X). Arrows indicate polymorphonuclear cells. Lung inflation was maintained by providing 20 cm H2O of continuous positive airway pressure. Bar = 100 µm
Fig. 3 Mucosubstance on tracheal epithelia
Images of mucus cells in rabbit tracheal epithelia of the control (A), Low Volume (B), High Volume (C) and High Pressure (D) groups (PAS/AB 400X). Black arrows indicate representative neutral mucus, white arrows indicate representative acid mucus and spotted black arrows indicate residual neutral mucus. Bar = 100 µm