Sublethal Trauma Research Articles

Ecological Constraints on Violence Avoidance Tactics in the Prehispanic Central Andes

ABSTRACT Prehispanic agricultural populations in the central Andes exhibit some of the highest rates of lethal and sublethal trauma ever recorded. Explanations for high rates of violence focus on what factors drove proactive conflict. While it is true that incentives for proactive violence must exist for high rates of trauma to ensue, it is far less recognized how ecological conditions may promote economic activities that constrain violence avoidance tactics and thus influence rates of violence. Here, we draw on models from behavioral ecology to generate predictions about how violence co-varies with environmental gradients, related subsistence strategies, and attendant defensive tactics. We hypothesize that rates of violence will be highest in marginal and variable environments where high-mobility subsistence strategies serve to reduce subsistence risk while increasing the costs of violence avoidance. Our results show that high elevation locations with variable topography where high mobility subsistence strategies are common exhibit the highest rates of generalized interpersonal violence. These results suggest that as ecological conditions become marginal and variable, risk-reducing subsistence strategies are emphasized, which result in increased exposure to violence. This study shows that environmental influences on the efficacy of violence avoidance tactics are important for explaining variability in rates of violence.

Erythrocyte morphological symmetry analysis to detect sublethal trauma in shear flow

The viscoelastic properties of red blood cells (RBC) facilitate flexible shape change in response to extrinsic forces. Their viscoelasticity is intrinsically linked to physical properties of the cytosol, cytoskeleton, and membrane—all of which are highly sensitive to supraphysiological shear exposure. Given the need to minimise blood trauma within artificial organs, we observed RBC in supraphysiological shear through direct visualisation to gain understanding of processes leading to blood damage. Using a custom-built counter-rotating shear generator fit to a microscope, healthy red blood cells (RBC) were directly visualised during exposure to different levels of shear (10–60 Pa). To investigate RBC morphology in shear flow, we developed an image analysis method to quantify (a)symmetry of deforming ellipsoidal cells—following RBC identification and centroid detection, cell radius was determined for each angle around the circumference of the cell, and the resultant bimodal distribution (and thus RBC) was symmetrically compared. While traditional indices of RBC deformability (elongation index) remained unaltered in all shear conditions, following ~100 s of exposure to 60 Pa, the frequency of asymmetrical ellipses and RBC fragments/extracellular vesicles significantly increased. These findings indicate RBC structure is sensitive to shear history, where asymmetrical morphology may indicate sublethal blood damage in real-time shear flow.

A Flow Induced Autoimmune Response and Accelerated Senescence of Red Blood Cells in Cardiovascular Devices

Red blood cells (RBCs) passing through heart pumps, prosthetic heart valves and other cardiovascular devices undergo early senescence attributed to non-physiologic forces. We hypothesized that mechanical trauma accelerates aging by deformation of membrane proteins to cause binding of naturally occurring IgG. RBCs isolated from blood of healthy volunteers were exposed to high shear stress in a viscometer or microfluidics channel to mimic mechanical trauma and then incubated with autologous plasma. Increased binding of IgG was observed indicating forces caused conformational changes in a membrane protein exposing an epitope(s), probably the senescent cell antigen of band 3. The binding of immunoglobulin suggests it plays a role in the premature sequestration and phagocytosis of RBCs in the spleen. Measurement of IgG holds promise as a marker foreshadowing complications in cardiovascular patients and as a means to improve the design of medical devices in which RBCs are susceptible to sublethal trauma.

Ultrastructural changes in red blood cells in aortic dissection patients under extracorporeal circulation: Atomic force microscopy study.

During extracorporeal circulation in heart surgery, blood is exposed to non-physiological conditions, such as high shear stress, foreign surfaces, turbulence, and hypothermia. These factors cause damage to the red blood cells, which is manifested by immediate and delayed hemolysis or some changes in the mechanical properties of red blood cells, defined as sublethal trauma. Unfortunately, sublethal trauma is hard to detect, and there is not enough morphological evidence regarding red blood cell sublethal trauma. In this study, red blood cell sublethal trauma was observed after extracorporeal circulation by describing ultrastructural changes in red blood cell membranes using atomic force microscopy and scanning electron microscopy. Venous blood (2 mL) was collected into heparin tubes from preoperative, intraoperative and postoperative aortic dissection patients for comparison with blood from healthy patients. The red blood cell morphological study (malformations percentage, diameter, height, concavity, and roughness) was performed with scanning electron microscopy and atomic force microscopy. Scanning electron microscopy and atomic force microscopy imaging analysis revealed that the red blood cell shape changed during extracorporeal circulation and that the red blood cell malformation percentage in the postoperative group was higher than those in the preoperative and intraoperative groups. Most morphological parameters had no obvious changes, except roughness (Ra and Rq) in aortic dissection patients. Atomic force microscopy quantitative analysis indicated that the roughness of red blood cell membranes increased during extracorporeal circulation. This study demonstrates that ultrastructural morphological damage occurs to red blood cells membranes due to extracorporeal circulation in aortic dissection patients. In addition, we provided a new parameter (Ra and Rq) to evaluate red blood cell sublethal trauma.

Mechanical blood trauma in assisted circulation: sublethal RBC damage preceding hemolysis.

After many decades of improvements in mechanical circulatory assist devices (CADs), blood damage remains a serious problem during support contributing to variety of adverse events, and consequently affecting patient survival and quality of life. The mechanisms of cumulative cell damage in continuous-flow blood pumps are still not fully understood despite numerous in vitro, in vivo, and in silico studies of blood trauma. Previous investigations have almost exclusively focused on lethal blood damage, namely hemolysis, which is typically negligible during normal operation of current generation CADs. The measurement of plasma free hemoglobin (plfHb) concentration to characterize hemolysis is straightforward, however sublethal trauma is more difficult to detect and quantify since no simple direct test exists. Similarly, while multiple studies have focused on thrombosis within blood pumps and accessories, sublethal blood trauma and its sequelae have yet to be adequately documented or characterized. This review summarizes the current understanding of sublethal trauma to red blood cells (RBCs) produced by exposure of blood to flow parameters and conditions similar to those within CADs. It also suggests potential strategies to reduce and/or prevent RBC sublethal damage in a clinically-relevant context, and encourages new research into this relatively uncharted territory.

Sublethal Trauma Model With Systemic Endotoxemia for the Study of Microcirculatory Disorders After the Second Hit

Experimental models often cannot simulate the clinical situation in traumatized patients where the septic second hit finally leads to multiple organ dysfunction syndrome and death. We present an experimental animal model combining initial standardized soft tissue trauma to the left hindlimb of rats with subsequent sublethal systemic endotoxemia. This study characterizes the influence of trauma and systemic endotoxemia on nutritive blood flow, inflammatory cell-cell interaction and tissue cell integrity in the traumatized region. At 24 h after local tissue contusion, in vivo analysis of the skeletal muscle microcirculation by means of high resolution fluorescence microscopy revealed intravascular leukocyte accumulation and impairment of nutritive perfusion with tissue hypoxia. Moreover, muscle tissue damage was characterized by myocyte cell apoptosis. Additional systemic exposure of animals to E. coli lipopolysaccharide at 6 h after soft tissue contusion caused a drop in arterial blood pressure as well as coagulatory disorders, as given by marked thrombocytopenia and reduced thromboplastin times. In double-hit exposed animals, skeletal muscle microcirculation presented with an aggravation of inflammation, perfusion failure, and apoptotic cell death after 24 h. This model more closely resembles the scenario of polytraumatized patients with the risk of secondary infections and, thus, is suited to characterize anti-inflammatory drugs with respect to their potential to interfere with microcirculatory disorders and elaboration of disseminated intravascular coagulation after trauma.

Pulmonary alveolar macrophage lysosomal enzyme activity after sublethal rotational trauma

The purpose of this study was to determine changes in pulmonary alveolar macrophage (PAM) lysosomal enzyme activity after sublethal trauma. PAMs from rats were isolated, and the activity of PAM lysosomal enzymes measured in control rats and rats subjected to Noble-Collip drum (NCD) sublethal trauma. Rats subjected to NCD trauma had a decrease in PAMs recovered; as well as total lysosomal enzyme activity compared to control PAMs analyzed immediately after isolated or after incubation in vitro. This decrease in lysosomal activity was seen in the 1600 g and lysosome-rich 10,000 g subcellular fractions. No immediate increase in lysosomal activity in the bronchopulmonary lavage was found. After the PAMs were incubated in vitro for 120 min, there was a significant release of enzyme activity into the incubation medium. Electron microscopic study of PAMs from the rats supported the biochemical observations. We feel that the reduction in PAM lysosomal enzyme activity after sublethal trauma may be an important mechanism which predisposes the animal to pulmonary infection.

Phagocytic and bactericidal activities of pulmonary macrophages following sublethal traumatic shock.

SummaryThe in vitrophagocytic and bactericidal responses of rat alveolar macrophages were investigated following sublethal traumatic shock. Phagocytosis of relabeled Pseudomonas aeruginosa by lung macrophages was elevated 1 hr post-trauma in the absence of bacterial opsonins. This response was transient with a return to normal by 24 hr. Bacterial phagocytosis by control and trauma alveolar macrophages was doubled in the presence of serum obtained either prior to or following trauma. In association with this acute phagocytic activation, resting 02consumption as well as bactericidal activity was stimulated in isolated alveolar macrophages harvested at 60 min post-traumatic injury. In contrast, the recoverable yields of lung macrophages following traumatic injury were significantly reduced at both the 1-hr and 24-hr postinjury period. Alveolar macrophage phagocytosis and metabolism are thus rapidly and transiently activated following host defense mechanisms following sublethal trauma. This response is in dir...

Correlation of plasma lysosomal enzyme levels with hepatic reticuloendothelial function after trauma.

Plasma lysosomal enzyme levels and hepatic phagocytosis were determined following Noble-Collip drum trauma in the rat. Circulating cathepsin and acid phosphatase activity increased after sublethal trauma (300 rev), reaching maximal levels at 1-3 hr and returning to pretrauma levels at 24 hr after trauma. Hepatic phagocytosis was decreased maximally at 1 hr and recovered to control levels at 24 hr after sublethal trauma. Increasing trauma intensity (100-500 rev) resulted in a progressive failure in hepatic Kupffer cell phagocytosis and a progressive increase in plasma lysosomal enzyme levels when tested at 60-min post-trauma. A significant inverse correlation was found between the plasma lysosomal enzyme levels and Kupffer cell phagocytosis after trauma. The functional significance of the relationship between these two parameters and its importance in shock survival remain to be determined.

Comparative effect of heparin and other agents on traumatic shock in the rat.

The effect of heparin and Aureomycin on Noble-Collip drum shock in rats was compared with that of autonomic blocking agents. Intravenous Dibenzyline (0.5 and 1.0 mg/kg) and Mecamylamine (2 mg/kg) notably reduced mortality when given 15–30 minutes prior to drumming. Heparin (2.5–10 mg/kg) and Aureomycin by mouth (150 mg/kg/day for 3 days) had no effect on mortality. Repeated sublethal trauma induced marked protection against drum shock. Concurrent administration of Dibenzyline did not prevent the development of this resistance. Repeated nonspecific stress and exercise failed to protect rats against drum shock suggesting that the development of ‘induced resistance’ is not related to elevated plasma catechol amines. The increased mortality of rats to drum shock incident to reticulo-endothelial blockade was mitigated if Dibenzyline was injected before blockade although not if given after.