Modeling Acute Traumatic Hemorrhagic Shock Injury: Challenges and Guidelines for Preclinical Studies

Shock
Jordi L TremoledaKarim Brohi

Abstract

Trauma is responsible for a large proportion of the world's burden of disease, and is by far the biggest killer of young adults. Hemorrhage is the leading cause of preventable death and its effects are directly correlated with the incidence multi-organ failure in survivors. Trauma research is challenging due to patient heterogeneity, limited randomized controlled trials, and in vitro studies that fail to mimic the systemic injury response. Preclinical research remains essential for mechanistic and therapeutic discovery. Yet modeling the multifaceted nature of traumatic injury poses important experimental and welfare challenges associated with the onset of injury and prehospital and intra-operative care, the limited inter-species validation of coagulation profiles, the use of anesthesia/analgesia, and its impact on the systemic response to trauma; and the challenge of sustaining intensive care in recovery models. Proper model selection depends on the purpose of a given model and the criteria by which the experimental readouts will be clinically relevant. Such complexity warrants further refinement of experimental methodology and outcome measures to improve its clinical efficacy, while ensuring animal well-being. We review the ex...Continue Reading

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Citations

Nov 15, 2017·Shock·Matthew J Delano, Krishnan Raghavendran
Mar 15, 2018·The Journal of Trauma and Acute Care Surgery·Penny S ReynoldsRamesh Natarajan
Feb 20, 2020·Military Medicine·Penny S Reynolds, Cynthia S Garvan
Mar 19, 2020·Shock·Fatemeh FattahiPeter A Ward
Sep 29, 2020·Immunology·Jessica Katy Skelton, Robert Purcell
Sep 18, 2020·Shock·Penny S Reynolds, Cynthia W Garvan
Aug 7, 2021·Stem Cell Research & Therapy·Clotilde AusselJuliette Peltzer

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