Pre-injury statins in early resuscitation of complex battlefield injuries

Poon, Henrietta (2021). Pre-injury statins in early resuscitation of complex battlefield injuries. University of Birmingham. Ph.D.

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Abstract

The Defence Medical Services faces many challenges when treating personnel injured on the battlefield. These include logistical constraints, such as limited resources, and prolonged evacuation times, as well as the physiological and immunological responses in the host as a result of traumatic injury. Injuries from explosions can include injuries caused by the shock wave that interact with the physiological and inflammatory responses to 'conventional’ trauma. The result can be an augmented inflammatory state, which may lead to systemic disease and remote organ damage. The use of pharmacological adjuncts to resuscitation may mitigate these inflammatory responses. Statins are potential candidates because of their pleiotropic properties such as organ protection and anti-inflammatory effects. The beneficial pleiotropic have been widely reported in ischaemia-reperfusion injury, and to a much lesser extent after haemorrhagic shock.

The study utilised a rat model of complex battlefield injury, which comprised femur fracture (tissue injury) and haemorrhage, with and without blast injury. The study was conducted in two strands (injury with and without blast), and within each strand the animals were randomised to receive either simvastatin or placebo. Outcome measures include DAMPS, cytokines, chemokines, circulating endothelial cells and histological changes, as well as physiological parameters such as blood pressure and acid-base status (degree of shock).

The injury, shock state and the resuscitation regimen in this model generated the expected physiological changes, and a measurable inflammatory response, which were both statistically and clinically significant. However, there was no statistically significant difference between treatment groups in either injury strand. These results suggest that treatment with simvastatin does not modify the response to trauma in either of the models of trauma used in this study.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):