Mechanical ventilation is the determining factor in inducing an inflammatory response in a hemorrhagic shock model Karlijn J.P. van Wessem, MD, a, * Marije P. Hennus, MD, b Marjolein Heeres, MD, a,c Leo Koenderman, PhD, c and Luke P.H. Leenen, MD, PhD a a Department of Trauma Surgery, University Medical Center Utrecht, Utrecht, The Netherlands b Department of Intensive Care, Wilhelmina Children’s Hospital, Utrecht, The Netherlands c Department of Respiratory Medicine, University Medical Center Utrecht, Utrecht, The Netherlands article info Article history: Received 15 August 2012 Received in revised form 1 October 2012 Accepted 11 October 2012 Available online xxx Keywords: Hemorrhagic shock Mechanical ventilation Neutrophils Pulmonary inflammation Systemic inflammation abstract Background: Hemorrhagic shock (HS) is known to induce an inflammatory response by activating the immune system. This response is mainly caused by primed poly- morphonuclear granulocytes (PMNs). Trauma patients often require mechanical ventila- tion (MV), which can cause additional pulmonary and systemic inflammation. The aim of this study was to evaluate the role of MV in the development of systemic and pulmonary inflammation in a HS model in rats. Materials and methods: In male SpragueeDawley rats, the effect of MV and HS on the systemic and pulmonary inflammatory responses was measured and compared. In five groups (control, sham, MV, HS, and MV þ HS), the inflammation was measured at time point 300 min after the start of the experiment. Results: The systemic inflammatory response, expressed in absolute numbers of PMNs in blood and blood growth related oncogene (GRO-KC) levels, was significantly higher in MV rats compared with that in other groups. The pulmonary inflammatory response, expressed by PMNs in bronchoalveolar lavage fluid (BALF), BALF interleukin 6, BALF GRO- KC, and myeloperoxidase activity, was significantly higher in all ventilated rats compared with that in the controls or HS rats. There was, however, no additional effect of HS in MV as the inflammatory indices were similar in both groups. Conclusions: Our data show that HS alone has minimal effect on the development of inflammation. MV (alone or in combination with HS) is the determining factor in inducing an inflammatory response. These results emphasize the importance of local (pulmonary) ventilation-induced damage in the development of systemic inflammation. ª 2012 Elsevier Inc. All rights reserved. 1. Introduction Hemorrhagic shock (HS) is known to trigger the innate immune system. Primed polymorphonuclear granulocytes (PMNs) play an important role in this activation [1e3]. Primed PMNs are prone to home and become activated in the tissues when they encounter additional local inflammatory stimuli. The lung is a preferred site for homing because of the large and narrow microvascular bed and long transit times [3]. Systemic neutrophil priming can cause excessive pulmonary neutrophil activation, which damages the lung endothelium. This can lead to increased alveolarecapillary permeability, * Corresponding author. Department of Trauma Surgery, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands. Tel.: þ31 88 75 598 82; fax: þ31 88 75 550 15. E-mail address: kwessem@umcutrecht.nl (K.J.P. van Wessem). Available online at www.sciencedirect.com journal homepage: www.JournalofSurgicalResearch.com journal of surgical research xxx (2012) 1 e8 0022-4804/$ e see front matter ª 2012 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jss.2012.10.019