Neurological outcome after experimental lung injury
Highlights
► In experimental ALI, an inflammatory response in the lung is followed by increase of systemic cytokines. ► After this animal model, lungs can effectively be recruited and animals can be weaned from the ventilator. ► Following lung injury, a testing of neurological outcome is feasible. Experimental ALI has significant effects on neurological outcome. The observed neurocognitive compromise after ALI seems due to a more pronounced inflammatory response and complex mechanical ventilation.
Introduction
Advances in the treatment of critically ill patients have led to improved survival among those admitted to an intensive care unit (ICU). Also among specific populations such as patients with acute respiratory distress syndrome (ARDS), survival rates, partly due to less invasive mechanical ventilation and new treatment options, have improved during the last years (The Acute Respiratory Distress Syndrome Network, 2000, Amato et al., 1998). As a consequence, several studies have focused on long term effects after ARDS (Hopkins et al., 2005a, Hopkins and Jackson, 2006).
Interestingly, 90% of critical care patients who underwent long-term mechanical ventilation (i.e. >5 days) exhibit a distinctive neurological impairment including memory deficits, language processing difficulties and cognitive decline (Hopkins et al., 2005b). In 70% of ARDS-survivors, these results are observed for several years (Hopkins et al., 2005a). However, the mechanisms that are of importance for this poor neurological outcome have not been fully explained yet.
It is known that cognitive decline and attenuation of memory is associated with structural changes in the hippocampus (Jackson et al., 2009, Manns et al., 2003, Hopkins et al., 1995a, Hopkins et al., 1995b). Whether or not refractory hypoxemia, which is common in ARDS, can be seen as the predominant mechanism contributing to neurological impairment, is not evident as previous studies have revealed different mechanisms independently from hypoxia (Fries et al., 2005, Bickenbach et al., 2009, Larsson et al., 2005). Hence, detailed mechanisms for the deterioration of neurologic function after ARDS remain unclear but may not only include hypoxia but also the effects of mechanical ventilation and, for example, its effects on the inflammatory response.
Regarding the acute phase after ARDS, cognitive decline has not been widely studied, and especially in an animal laboratory design, no data exists on post-experimental neurological examinations after experimental lung injury.
Thus, the purpose of this study was twofold:
First, we sought to determine the influence of two different methods for induction of hypoxia on functional neurological outcome and nervous tissues. We hypothesized that mechanical ventilation in ALI is associated with an increased neurologic deficit when being compared to hypoxia only.
Second, we wanted to establish a chronic animal model for the effects of early neurologic outcome after ALI.
Section snippets
Methods
The experimental protocol was approved by the appropriate governmental institution (Landesamt für Umwelt und Naturschutz, Recklinghausen, Germany) and the study was performed according to the Helsinki convention guidelines for the use and care of laboratory animals.
Results
For a stable lung injury in the ALI group, 8 ± 2 lavage procedures were necessary. In the HO group, a reduction of the to 0.13 ± 0.01 was needed.
Regarding neurocognitive performance, no significant differences between the two groups could be seen prior to the experiment. Over the ensuing post-experimental period, animals from the ALI group showed a significantly elongated time interval until food was found (Fig. 1).
For the NDS, significantly higher values could be shown for the ALI group at
Discussion
The present study demonstrated a significant influence of experimentally induced ALI on alteration in neurological performance as shown by a significant increase in neurocognitive testing and the NDS after the acute phase of experimental lung injury. However, these changes did only result in mild changes of histopathology in terms of perivascular inflammation in the hippocampal CA1 sector, the caudate nucleus and the putamen being not significantly different between the groups. In this regard,
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