Mechanisms Involved in Secondary Cardiac Dysfunction in Animal Models of Trauma and Haemorrhagic Shock.
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Clinical evidence reveals the existence of a trauma induced secondary cardiac injury (TISCI) which is associated with poor patient outcomes. The mechanisms leading to TISCI in injured patients are uncertain. Conversely, animal models of trauma haemorrhage have repeatedly demonstrated significant cardiac dysfunction following injury, and highlighted mechanisms through which this might occur. The aim of this review was to provide an overview of the animal studies describing TISCI and its pathophysiology.Basic science models of trauma show evidence of innate immune system activation via Toll-Iike receptors (TLRs), the exact protagonists of which remain unclear. Shortly following trauma and haemorrhage, cardiomyocytes upregulate gene regulatory protein and inflammatory molecule expression including Nuclear factor kappa beta (NF-κB), tumour necrosis factor alpha (TNFα) and interleukin-6 (IL-6). This is associated with expression of membrane bound adhesion molecules and chemokines leading to marked myocardial leukocyte infiltration. This cell activation and infiltration is linked to a rise in enzymes that cause oxidative and nitrative stress and subsequent protein misfolding within cardiomyocytes. Such protein damage may lead to reduced contractility and myocyte apoptosis. Other molecules have been identified as cardioprotective following injury. These include p38 mitogen-activated protein kinases (MAPK) and heat shock proteins.The balance between increasing damaging mediators and a reduction in cardio-protective molecules appears to define myocardial function following trauma. Exogenous therapeutics have been trialled in rodents with promising abilities to favourably alter this balance, and subsequently lead to improved cardiac function. (C) 2017 by the Shock Society
AuthorsWilson, NM; Wall, J; Naganathar, V; Brohi, K; De'Ath, HD
- College Publications