Establishment of an Experimental Mouse Model of Trauma-Hemorrhagic Shock

Abstract

This study established an experimental mouse model of trauma-hemorrhagic shock (THS). THS-induced mice (C57BL/6J, n=33) were subjected to femoral fracture, ischemia for 90 min, and resuscitation for 15 min. The sham-operated mice (C57BL/6J, n=33) underwent the same anesthetic and surgical procedures, but neither trauma-hemorrhage nor fluid resuscitation were performed. Mean arterial pressure (MAP) and microvascular tissue perfusion over the small intestine, liver, and left kidney were longitudinally measured in all mice. Blood was collected for analysis at baseline and 3, 6, 12, and 24 h post resuscitation, and the small intestine, liver, and left kidney were resected for hematoxylin and eosin staining 24 h post resuscitation. Compared with the sham group, MAP and microvascular tissue perfusion over the small intestine, liver, and left kidney were all significantly reduced in the THS group at the end of hemorrhage. Following resuscitation, no significant differences were observed between the groups. THS induction was associated with significantly increased plasma concentrations of Cr, AST, CPK, IL-6, IL-10, and TNF-α from the baseline values by two-to three-fold after the hemorrhage phase, and THS-induced mice demonstrated significantly increased histological injury scores. The rapid drop in MAP and microvascular tissue perfusion observed following THS induction, and the gradual recovery post resuscitation, reflects the successful establishment of a THS experimental mouse model.

Temporal profile of inflammatory response to fracture and hemorrhagic shock: Proposal of a novel long-term survival murine multiple trauma model

“…In the past, numerous reports describing animal models for the study of multiple trauma, incl. fracture and hemorrhagic shock have been published . These studies demonstrated dysfunction of posttraumatic immune response, changes in IL‐6 expression following multiple trauma and hemorrhagic shock or tested the efficacy of rejuvenation of the immune system by bone marrow transplantation on fracture repair .…”

“…Several authors publish hemorrhagic shock models in combination with sepsis or isolated limb injury . These studies using different models and fracture methods were restricted either to rats and mice that did either not survive the acute period (more than 72 h) or did not allow long‐term analysis of fracture healing.…”

“…In the well‐characterized hemorrhagic shock model of Tang et al multiple trauma animals did not survive longer than 24 h, again excluding long‐term study of fracture healing. The multiple trauma model of Probst et al used hemorrhagic shock induction via withdrawal of 60% blood volume by orbital puncture without macrohemodynamic and metabolic verification of shock .…”

“…However, systematic clinical trials and valid long‐term animal models that aim to study the impact of posttraumatic immune response on altered bone healing in multiple trauma are missing. Nearly all published animal models combining fracture and hemorrhagic shock do not allow analysis of completed bone healing due to limited survival . Therefore, establishment of a reliable and clinically relevant long‐term animal model closely mimicking typical injury patterns and severity are essentially needed.…”

Helping prometheus: liver protection in acute hemorrhagic shock

“…Under normotensive conditions circulating leukocytes flow freely through the sinusoids of the liver, evoking no interactions with the vascular endothelium. Circulatory disturbance results in sinusoidal congestion with increased leukocyte activation (21,22) as well as increased leukocyte endothelial interactions (7).…”