Mechanical ventilation is the determining factor in inducing an inflammatory response in a hemorrhagic shock model

Abstract

Background

Hemorrhagic shock (HS) is known to induce an inflammatory response by activating the immune system. This response is mainly caused by primed polymorphonuclear granulocytes (PMNs). Trauma patients often require mechanical ventilation (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 Sprague–Dawley 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 + 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.

Introduction

Hemorrhagic shock (HS) is known to trigger the innate immune system. Primed polymorphonuclear granulocytes (PMNs) play an important role in this activation [1], [2], [3]. 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 alveolar–capillary permeability, protein leakage, production of inflammatory mediators, and eventually impaired gas exchanges such as seen in acute lung injury and acute respiratory distress syndrome [1], [2], [3], [4], [5].

Mechanical ventilation (MV), as often used to support multitrauma patients in the first phase after the accident, can cause injury to the lung depending on the strategy and ventilation mode or attribute to already existing lung damage [6], [7], [8], [9]. Inflammatory effects seen in HS and ventilator-induced lung injury seem comparable [10], [11]. However, it is unknown whether a combination of HS and MV will have a synergistic effect on these inflammatory responses. If a synergistic effect could be demonstrated, a change in ventilatory regimen might attribute to an improved clinical outcome.

To determine the effects of both systemic and local injury on the systemic inflammatory response, a HS rat model combined with injurious (high pressure and high tidal volume) ventilation was designed. It was hypothesized that a combination of HS and MV would cause a more severe inflammatory response compared with either HS or MV alone. A possible synergy could be of clinical relevance as an increased inflammatory response might cause more inflammation-related complications.