Autodigestion in Hemorrhagic Shock and Acute Heart.. (CelSys Shock)
Autodigestion in Hemorrhagic Shock and Acute Heart Failure: a Cell-to-System Approach to Pathophysiology and Therapy
Start date: Jan 1, 2014,
End date: Dec 31, 2016
"The relationship between hemorrhagic shock, systemic inflammatory response syndrome, and multiple organ failure has long been investigated, but no accepted tissue injury mechanism has been assessed. This shortage of understanding of the basic pathophysiology limits the clinical management of one of the most important medical conditions from a mortality point of view, with implications in anesthesia and critical care.In this proposal, a new approach to the study of the molecular triggers of shock is proposed, on the basis of the innovative framework of the ""Autodigestion Hypothesis"". The goals are to identify the root cause of hemodynamic instability and specifically of shock induced acute heart failure, and to propose therapeutic countermeasures for its prevention and treatment.An animal model of hemorrhagic shock in the rat will be used for experimental induction of hemorrhage and resuscitation, with the aim of shedding light on the potential cleavage of important receptors in the heart due to the proteolytic action of digestive enzymes and matrix metalloproteinases.A multiscale approach to data analysis will be formulated to describe the pathogenesis of shock, from the cellular and molecular phenomena to its system wide symptoms, and to predict the occurrence of hemodynamic instability, hypotension and heart failure from the information conveyed by hemodynamic vital signs which are commonly accessible in critical care or emergency settings.The training implications of this project will enable the fellow to receive high level training on state-of-the-art molecular cardiovascular physiology and disease, and to complement his current skills in hemodynamic signal processing and modeling, granting him the opportunity to expand his current interests and background and to achieve a complete profile and independence as a researcher in the cardiovascular field."
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