Trauma-induced secondary cardiac injury (TISCI) represents an under recognised complication of severe injury with haemorrhage. A limited number of clinical studies have supported the development of adverse cardiac events, such as arrhythmia, in association with biomarker proven TISCI. Pre-clinical studies using small animal models have provided insights into potential mechanisms and key effector molecules involved in the development of TISCI, but there remains a general lack of understanding regarding the in vivo functional implications of this indirect cardiac injury resulting from trauma-haemorrhage. This project aimed to investigate the implications of cardiac injury on myocardial systolic function. A robust, translatable model of TISCI was developed, which reflected the cardiac biomarker profile identified in clinical studies and, for the first time, demonstrated a significant, dose-dependent rise in Heart-type Fatty Acid Binding Protein (H-FABP) in response to trauma-haemorrhage. Non-invasive echocardiography was used to determine the acute myocardial response to injury and haemorrhage and also to assess the response of the left ventricle to resuscitation after an antecedent 60-minute period of trauma-haemorrhage. The functional studies presented here have enabled real time visualisation of the impact of trauma-haemorrhage upon systolic left ventricular function over 1 to 6 hours, both with and without resuscitation. Having established the trends in in vivo systolic function over time, further studies were then conducted to test the combination of adenosine, lidocaine and magnesium (ALM) as a cardiovascular rescue agent in TISCI. ALM, as an adjunct to fluid resuscitation, has shown great promise as a therapeutic agent which improves haemodynamic outcomes, reduces the volume of resuscitation fluid required and favours survival in the murine model of TISCI.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:766208 |
| Date | January 2018 |
| Creators | Wall, Johanna Martine |
| Publisher | Queen Mary, University of London |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://qmro.qmul.ac.uk/xmlui/handle/123456789/43998 |
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