PhD ceremony Ms. F.M. Wulfert: In vivo endothelial cell and neutrophil responses to shock

PhD ceremony: Ms. F.M. Wulfert

Dissertation: In vivo endothelial cell and neutrophil responses to shock

Promotors(s): prof. G. Molema, prof. J.G. Zijlstra, prof. M.M.R.F. Struys

Faculty: Medical Sciences

Multi-organ dysfunction syndrome (MODS) following shock states is still a major determinant of morbidity and mortality. Besides a package of supportive measures, which are aimed at limiting and managing the systemic, multi-system consequences of sepsis and trauma, there is until now no clinical treatment available directed at the cause of MODS. The endothelium is an important player in the pathogenesis of MODS, as it facilitates neutrophil migration in tissue, which is thought to play a pivotal role in organ dysfunction. We hypothesize that understanding the spatial-temporal pattern of endothelium activation in shock states can assist in identifying new rational targets for early therapeutic interventions to prevent the development of MODS. In this thesis, we employed mouse models to investigate the microvascular responses to shock induced stress. From our studies we concluded that during shock states there is early organ and vascular bed specific activation of the endothelium. To further investigate the role of neutrophils we used a model in which neutrophils were depleted. In the next part we employed a mechanical ventilation model since in the clinic patient are often mechanically ventilated. Because elderly are at higher risk to develop MODS we next performed our studies in young and old mice to investigate if endothelial activation is different in elderly. We concluded from our studies that it is important to investigate endothelial cells on their location in the body since their behavior is heterogenetic. Endothelial activation might have a different course in elderly, thus it is important to take this into account in future research.