Role of Hemorrhagic Shock in Experimental Polytrauma

Abstract

Hemorrhagic shock (HS) after tissue trauma increases the complication and mortality rate of polytrauma (PT) patients. Although several murine trauma models have been introduced, there is a lack of knowledge about the exact impact of an additional HS. We hypothesized that HS significantly contributes to organ injury, which can be reliably monitored by detection of specific organ damage markers. Therefore we established a novel clinically relevant PT plus HS model in C57BL/6 mice which were randomly assigned to control, HS, PT, or PT+HS procedure (n = 8 per group). For induction of PT, anesthetized animals received a blunt chest trauma, head injury, femur fracture, and soft tissue injury. HS was induced by pressure-controlled blood drawing (mean arterial blood pressure of 30 mmHg for 60 min) and mice then resuscitated with ionosterile (4 × volume drawn), monitored, and killed for blood and organ harvesting 4 h after injury. After HS and resuscitation, PT+HS mice required earlier and overall more catecholamine support than HS animals to keep their mean arterial blood pressure. HS significantly contributed to the systemic release of interleukin-6 and high mobility group box 1 protein. Furthermore, the histological lung injury score, pulmonary edema, neutrophil influx, and plasma clara cell protein 16 were all significantly enhanced in PT animals in the presence of an additional HS. Although early morphological changes were minor, HS also contributed functionally to remote acute kidney injury but not to early liver damage. Moreover, PT-induced systemic endothelial injury, as determined by plasma syndecan-1 levels, was significantly aggravated by an additional HS. These results indicate that HS adds to the systemic inflammatory reaction early after PT. Within hours after PT, HS seems to aggravate pulmonary damage and to worsen renal and endothelial function which might overall contribute to the development of early multiple organ dysfunction.

Thirty-eight-negative kinase 1 mediates trauma-induced intestinal injury and multi-organ failure

“…First, we examined whether TNK1 expression would change in response to various severe traumatic stressors using a mouse model of experimental trauma. Anesthetized mice were subjected to a sham procedure or polytrauma in the presence or absence of an additional hemorrhagic shock as described previously (37). TNK1 transcripts were significantly increased in the small intestine and colon already 4 hours after trauma induction ( Figure 5A).…”

Innate immune responses to trauma

“…Ischemic and inflammatory conditions often result in the disruption of both tight junctions (TJs) (for example, claudins) and glycocalyx components (for example, glucosaminoglycans (GAGs)), as well as their being shed into the intravascular space, as detected very early in clinical and experimental polytrauma 62–65 . In addition, the abundance of the bioactive lipid S1P, a preserver of endothelial integrity, is diminished in the plasma of patients who have suffered polytrauma; this unleashes metalloproteinase activity that contributes to damage to protective GAGs 66 .…”

“…Early after polytrauma, the interaction of innate immunity and the endothelium can become hyperactivated, especially in the presence of an additional hemorrhagic shock 65 . The defensive features of neutrophils can then result in the excessive release of proteases, massive generation of ROS, shedding of pro-inflammatory microparticles 29,30 , antiapoptotic features 37 , a prothrombotic surface 29 and immuno-metabolic changes that generate a lactate-acidic microenvironment, as has been shown both in vitro and in vivo after exposure to C5a 70 .…”

Platelets and Fibrinogen: Emerging Complexity in Trauma-Induced Coagulopathy

“…Oxidants can be generated in blood after trauma by a release of oxidative enzymes such as myeloperoxidase and nitric oxide synthase in response to inflammation and vascular shock, respectively. [27][28][29] These enzymes generate damaging oxidants such as superoxide, peroxynitrite, and hypochlorous acid (HOCL) in the blood. Platelets and several important platelet ligands are sensitive to their local redox environment and use redox signaling to support their activation, having complex effects on platelet function.…”