Impaired Fracture Healing after Hemorrhagic Shock

Abstract

Impaired fracture healing can occur in severely injured patients with hemorrhagic shock due to decreased soft tissue perfusion after trauma. We investigated the effects of fracture healing in a standardized pressure controlled hemorrhagic shock model in mice, to test the hypothesis that bleeding is relevant in the bone healing response. Male C57/BL6 mice were subjected to a closed femoral shaft fracture stabilized by intramedullary nailing. One group was additionally subjected to pressure controlled hemorrhagic shock (HS, mean arterial pressure (MAP) of 35 mmHg for 90 minutes). Serum cytokines (IL-6, KC, MCP-1, and TNF-α) were analyzed 6 hours after shock. Fracture healing was assessed 21 days after fracture. Hemorrhagic shock is associated with a significant increase in serum inflammatory cytokines in the early phase. Histologic analysis demonstrated a significantly decreased number of osteoclasts, a decrease in bone quality, and more cartilage islands after hemorrhagic shock. μCT analysis showed a trend towards decreased bone tissue mineral density in the HS group. Mechanical testing revealed no difference in tensile failure. Our results suggest a delay in fracture healing after hemorrhagic shock. This may be due to significantly diminished osteoclast recruitment. The exact mechanisms should be studied further, particularly during earlier stages of fracture healing.

Analysis of skeletal muscle microcirculation in a porcine polytrauma model with haemorrhagic shock

“…Several studies have also shown that after resuscitation the local microcirculation disturbance appears to last for a longer period . This might be due to the post‐traumatic local and systemic increase of inflammation mediators, such as IL‐6 (Interleukin), IL‐8, IL‐10, HMGB 1 (High mobility group box 1) and TNF‐a (tumor necrosis factor alpha) . These mediators may affect the local perfusion by influencing the tone of the vessels and metabolism of the local tissue .…”

NPY and CGRP Inhibitor Influence on ERK Pathway and Macrophage Aggregation during Fracture Healing

“…Fracture healing is a complex process involving the interplay of various types of cells, cytokines, growth factors and extracellular environment [2-4]. The inflammatory response after injury also plays a significant role in bone healing by regulating endochondral ossification and bone remodeling [5]. Several investigations identifying the diverse regulatory molecules during fracture recovery have been conducted, among which the neurotransmitters were of our particular interest and have been considered as critical regulators in fracture healing.…”

Severe Hemorrhagic Shock Leads to a Delayed Fracture Healing and Decreased Bone Callus Strength in a Mouse Model

“…These findings are contrary to our results of a decreased density of bone including callus in the THFx group after 2 weeks. Biomechanical analyses by Lichte et al [16], Bumann et al [6], and Starr et al [27] showed no differences after biomechanical testing between Fx and THFx groups. Lichte et al [16] found no difference in failure strength between the Fx and THFx groups after 3 weeks.…”

“…Starr et al [27] conducted radiographic analyses on callus area and density and found analogous to our results no differences between Fx and THFx groups in weekly examinations up to 4 weeks after surgery in a goat model. Lichte et al [16] performed a lCT analysis in a study setting which was similar to our model. They observed delayed fracture healing in the THFx group after 3 weeks in mice via histologic analysis, but found no differences in bone mineral density, tissue mineral density, and bone volume versus tissue volume analyzed by lCT.…”

“…Conflicting results have been reported in experimental studies investigating fracture healing after severe blood loss in animals. Wichmann et al [28] and Lichte et al [16] reported that trauma hemorrhage leads to increased osteocyte necrosis and delayed fracture healing. By contrast, Lucas et al [17] and Bumann et al [6] reported a positive effect of trauma hemorrhage on fracture healing, including an increased rate of mineralization and osteoblast number and better vascularization of the fracture zone.…”