Traumatic shock and electroshock: the difficult relationship between anatomic pathology and psychiatry in the early 20th century.

In the conviction that a look at the past can contribute to a better understanding of the present in the field of science too, we discuss here two aspects of the relationship between early 20th century anatomic pathology and psychiatry that have received very little attention, in Italy at least. There was much debate between these two disciplines throughout the 19th century, which began to lose momentum in the early years of the 20th, with the arrival on the scene of schizophrenia (a disease histologically sine materia) in all its epidemiological relevance.The First World War also contributed to the separation between psychiatry and pathology, which unfolded in the fruitless attempts to identify a histopathological justification for the psychological trauma known as shell shock. This condition was defined at the time as a "strange disorder" with very spectacular symptoms (memory loss, trembling, hallucinations, blindness with no apparent organic cause, dysesthesias, myoclonus, bizarre postures, hemiplegia, and more), that may have found neuropathological grounds only some hundred years later.Among the doctors with a passed involvement in the conflict, Ugo Cerletti, the inventor of electroshock treatment, focused on the problem of schizophrenia without abandoning his efforts to identify its organic factors: if inducing a controlled electric shock, just like an experimentally-induced epileptic seizure, seems to allay the psychotic symptoms and heal the patient, then what happens inside the brain? In seeking histological proof of the clinical effects of electroconvulsive therapy ("the destruction of the pathological synapses"), and attempting to isolate molecules (that he called acroagonins) he believed to be synthesized by neurons exposed to strong electric stimulation, Cerletti extended a hand towards anatomic pathology, and took the first steps towards a neurochemical perspective. However his dedication to finding a microscopic explanation for schizophrenia - in the name of a "somatist" approach that, some years earlier, the psychiatrist Enrico Morselli had labelled "histomania" - was unable to prevent psychiatry from moving further and further away from anatomic pathology.

Efficacy of Uncross-Matched Type O Packed Red Blood Cell Transfusion to Traumatic Shock Patients: a Propensity Score Match Study.

A new blood bank system was established in our trauma bay, which allowed immediate utilization of uncross-matched type O packed red blood cells (UORBCs). We investigated the efficacy of UORBC compared to that of the ABO type-specific packed red blood cells (ABO RBCs) from before the bank was installed. From March 2016 to February 2017, data from trauma patients who received UORBCs in the trauma bay were compared with those of trauma patients who received ABO RBCs from January 2013 to December 2015. Propensity matching was used to overcome retrospective bias. The primary outcome was 24-hour mortality, while the secondary outcomes were in-hospital mortality and intensive care unit (ICU) length of stay (LOS). Data from 252 patients were reviewed and UORBCs were administered to 64 patients. The time to transfusion from emergency room admission was shorter in the UORBC group (11 [7-16] minutes vs. 44 [29-72] minutes, P < 0.001). After propensity matching, 47 patients were included in each group. The 24-hour mortality (4 [8.5%] vs. 9 [13.8%], P = 0.135), in-hospital mortality (14 [29.8%] vs. 18 [38.3%], P = 0.384), and ICU LOS (9 [4-19] days vs. 5 [0-19] days, P = 0.155) did not differ significantly between groups. The utilization of UORBCs resulted in a faster transfusion but did not significantly improve the clinical outcomes in traumatic shock patients in this study. However, the tendency for lower mortality in the UORBC group suggested the need for a large study.

[THE PRINCIPLES OF ORGANIZATION AND TREATMENT FOR SORTING OF WOUNDED PERSONS WITH A COMBAT SURGICAL TRAUMA OF EXTREMITIES ON THE IV LEVEL OF THE MEDICAL CARE PROVISION].

Experience of medical sorting of 434 injured persons with a gun-shot woundings of extremities in 2014-2015 yrs is adduced. The principles of organization and treatment for medical sorting of wounded persons were elaborated. Prognostic intrahospital, diagnostic and evacuation--transport sorting was introduced in wounded persons in the IV level hospital, concerning severity of traumatic shock and prognosis of their survival.

[PROGNOSIS OF INFECTIVE COMPLICATIONS OF THE GUN-SHOT WOUNDS OF SOFT TISSUES].

The method of prognostication of infectious complications in a gun-shot wound was elaborated, using the methods of logistic regression analysis.

Traumatic injuries to the craniovertebral junction: a review of rare events.

The craniovertebral junction is a specific region of the spine with unique anatomical and biomechanical properties that yields a wide variety of injury patterns. Junctional traumatic fractures and/or dislocations are widely reported in clinical practice, but we could identify only a subgroup of upper cervical spine traumatic injuries with very few cases reported in the literature, and for this reason may be considered rare. In some of these cases, the absence of spinal biomechanical instability, in association with moderate clinical symptoms (neck stiffness and pain) and the difficulty in fracture identification through standard cervical radiographs, leads to a high percentage of missed injuries. In other cases, traumatic events have been commonly described only in autopsy series due to the high degree of spinal biomechanical instability. Herein, we have summarized all the relevant literature concerning this issue and also included our cases, with the aim of emphasizing prompt diagnosis and correct management. We provide a guide for correctly identifying "rare" craniovertebral junction traumatic injuries.

[Expression of VCAM-1 and caspase-3 in myocardium of persons who died from viral myocarditis].

OBJECTIVE: To observe the expression and distribution of vascular cell adhesion molecule-1 (VCAM-1) and caspase-3 in myocardium of persons who died from viral myocarditis and to explore its pathogenesis and death mechanism. METHODS: Twenty cases died from viral myocarditis were selected as the experimental group. Ten cases died from traumatic shock and massive hemorrhage shock after traffic accidents were selected as the control group. The sections of myocardium were stained by immunohistochemistry for VCAM-1 and caspase-3, and observed under microscope. The positive expressions of VCAM-1 and caspase-3 of the two groups were compared with each other by image analysis and statistical analysis. RESULTS: (1) The vascular endothelial cells expressed VCAM-1 with dark-brown colors in the experimental group, and weak expression was observed in the control group. The average optical density in the experimental group was higher than that in the control group (P < 0.05). (2) The caspase-3 positive cells were mostly inflammatory cells around the myocardial vessels with brown-red granules in the experimental group. The positive cell number in the experimental group was higher than that in the control group (P < 0.05). CONCLUSION: VCAM-1 may play an important role in the inflammatory cells exudation caused by viral myocarditis, and may provide the reference for diagnosis of viral myocarditis in forensic pathology. However, the myocardial apoptosis mediated by caspase-3 doesn't affect the lethal mechanism in the late stage of viral myocarditis.

Molecular pathology of pulmonary edema after injury in forensic autopsy cases.

The lung is vulnerable to trauma; pulmonary edema starts quickly as part of the systemic responses involved in shock. The present study investigated the molecular pathology of posttraumatic alveolar damage and responses involving pulmonary edema in forensic autopsy cases of injury (n = 66) compared with acute cardiac death cases (n = 13). Intrapulmonary mRNA and immunohistochemical expressions of matrix metalloproteinases (MMPs; MMP-2 and MMP-9), intercellular adhesion molecule-1, claudin-5, and aquaporins (AQPs, AQP-1 and AQP-5) were examined. Subacute injury deaths showed an increase in lung weight similar to that in acute cardiac death, but relative mRNA quantification using the Taqman real-time PCR assay demonstrated different findings among the causes of death; higher expressions were detected for all markers, except for AQP-5 in sharp instrument injury, for MMP-2 in blunt brain injury, and for MMP-9 in non-brain blunt injury, but these expression levels were lower in acute cardiac death. In immunostaining, only MMPs showed differences among the causes of death: MMP-2 expression was evident in most subacute deaths due to blunt brain injury and sharp instrument injury, whereas MMP-9 was intensely positive in those of non-brain blunt injury and sharp instrument injury. These findings suggest significant differences in the mechanism of pulmonary edema among fatal injuries and acute cardiac death, especially between blunt and sharp instrument injury. Systematic analysis of gene expressions using real-time PCR in combination with immunohistochemistry may be useful in evaluating pulmonary damage and responses after injury in death investigations, especially in connection with posttraumatic shock.

Data driven linear algebraic methods for analysis of molecular pathways: application to disease progression in shock/trauma.

MOTIVATION: Although trauma is the leading cause of death for those below 45years of age, there is a dearth of information about the temporal behavior of the underlying biological mechanisms in those who survive the initial trauma only to later suffer from syndromes such as multiple organ failure. Levels of serum cytokines potentially affect the clinical outcomes of trauma; understanding how cytokine levels modulate intra-cellular signaling pathways can yield insights into molecular mechanisms of disease progression and help to identify targeted therapies. However, developing such analyses is challenging since it necessitates the integration and interpretation of large amounts of heterogeneous, quantitative and qualitative data. Here we present the Pathway Semantics Algorithm (PSA), an algebraic process of node and edge analyses of evoked biological pathways over time for in silico discovery of biomedical hypotheses, using data from a prospective controlled clinical study of the role of cytokines in multiple organ failure (MOF) at a major US trauma center. A matrix algebra approach was used in both the PSA node and PSA edge analyses with different matrix configurations and computations based on the biomedical questions to be examined. In the edge analysis, a percentage measure of crosstalk called XTALK was also developed to assess cross-pathway interference. RESULTS: In the node/molecular analysis of the first 24h from trauma, PSA uncovered seven molecules evoked computationally that differentiated outcomes of MOF or non-MOF (NMOF), of which three molecules had not been previously associated with any shock/trauma syndrome. In the edge/molecular interaction analysis, PSA examined four categories of functional molecular interaction relationships--activation, expression, inhibition, and transcription--and found that the interaction patterns and crosstalk changed over time and outcome. The PSA edge analysis suggests that a diagnosis, prognosis or therapy based on molecular interaction mechanisms may be most effective within a certain time period and for a specific functional relationship.

[On the problem of traumatic shock associated with a combined injury (based on the materials of one forensic medical expertise)].

The author presents the results of the critical analysis of the materials of forensic medical expertise of a case of the serious harm to health that has led to involunry manslaughter. According to the expert opinion, the death resulted from the traumatic shock associated with the combined head and the chest injury. Such conclusion levels out the difference between the two accused persons and their "contribution" to the extent and severity of the inflicted damage to the victim's body; thereby, it equalizes the degree of their guilt and criminal responsibility. The present study showed that such interpretation of tanatogenesis associated with the combined injury is erroneous. The death of the injured person resulted from cerebral coma that developed following a severe craniocerebral injury as a constituent component of the combined trauma. It is emphasized that the thorough investigation of tanatogenesis based on the reliable elucidation of the immediate cause of death makes it possible to avoid poorly substantiated expert conclusions and their potential dire legal consequences.

Hydroxyethyl Starch Improves the Prognosis of Rats with Traumatic Shock via Activation of the ERK Signaling Pathway in Lymphocytes.

OBJECTIVE: Severe traumatic shock is one of the leading causes of death in young adults. A large number of studies have shown that effective volumetry resuscitation on the basis of controlled injury can not only increase the success rate of early resuscitation but also reduce systemic inflammatory response and improve the cure rate of severe traumatic shock. The study explored the effects of hydroxyethyl starch (HES) on the survival rate, lymphocyte function and proliferation of rats with traumatic shock, and the potential mechanisms. METHODS: Traumatic shock was constructed in rats as experimental model, and liquid resuscitation was performed using HES and lactated Ringer's (LR). 24-h mortality was recorded, and lymphocytes were isolated. The expressions of signaling pathway factors was detected by qPCR and Western blot. ELISA was performed to determine the expression of interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α) in cell supernatant. RESULTS: HES for fluid resuscitation augmented the survival of traumatic shock rats, upregulated the expressions of MEK and ERK1/2, and downregulated the expressions of IL-6 and TNF-α. However, inhibition of ERK signaling pathway reversed the effect of HES on the immune improvement and the 24-h survival rate of the traumatic shock rats (P < 0.05). CONCLUSION: HES could exert the anti-inflammatory effects on lymphocytes by mediating the phosphorylation of proteins of the ERK signaling pathway. HSE demonstrated a high efficacy in effectively treating traumatic shock, thus could be used in clinical practice.

[The effect of the membrane attack complex C5b-9 on liver cells during traumatic hemorrhagic shock in rat].

OBJECTIVE: To observe whether the membrane attack complex C5b-9 would accumulate in the rats' liver after receiving the assault of traumatic hemorrhagic shock, and whether the membrane attack complex deals an impact on liver apoptosis. METHODS: Fifty male healthy Wistar rats were randomly divided into five groups: normal group, 1, 3, 6, 24 hour model groups. The model of traumatic hemorrhagic shock was reproduced by withdrawal of blood from carotid artery after a bone fracture till the blood pressure lowered to 40 mm Hg (1 mm Hg=0.133 kPa). Plasma membrane attack complex C5b-9 concentration was assayed using enzyme linked immunoadsorbent assay. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in blood was determined by Rate method. Immunohistochemistry was used to detect C5b-9 deposition in the liver. Apoptosis of liver cells was then detected by the terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) assay. The pathological changes in paraffin sections stained with hematoxylin eosin (HE) were observed under light microscope. RESULTS: A small amount of C5b 9 in plasma was found in normal group, and the values (ng/L) of 1, 3, 6 hour models were significantly higher than those of the normal group (272.91 ± 9.56, 192.01 ± 9.04, 156.78 ± 8.37 vs. 25.98 ± 5.87, all <0.05 ). ALT (U/L) in 3 hour model group and AST (U/L) in 1 hour model group were increased significantly (92.90 ± 8.83, 264.83 ± 31.4), peaked at 24 hours (184.30 ± 12.98, 647.36 ± 60.02), and there was significant difference compared with normal group (38.75 ± 5.40, 66.69 ± 19.95, all P <0.05). In the normal group and the 1 hour and 6 hour model groups, no C5b 9 was found in liver, but in the 3 hour model group a large number of liver parenchymal cells in the portal area were found to contain C5b 9 22.60 ± 1.06), however the number decreased significantly in the 24 hour model (2.20 ± 0.60, P<0.05). In normal group there was no apoptotic cell, and in 1, 6, 24 hour model groups there were scattered apoptotic cells (1.20 ± 0.25, 5.60 ± 0.37, 1.60 ± 0.26). In the 3 hour model group apoptosis of hepatic cells around the central vein was increased to the peak (20.60 ± 0.47), and there was significant difference compared with other groups (all P <0.05) . In the model groups the liver cells became edematous, and the integrity of the membrane was lost, and some cells were even lysed.The pathological damage is most serious in 24 hour model group. CONCLUSION: The membrane attack complex C5b-9 insulted the rats' liver after a traumatic hemorrhagic shock, and apoptosis of hepatic cells and the content of C5b-9 peaked in 3 hour model , though they do not occur in the same site. A low level of C5b-9 in blood 3 hours after shock predict a poor prognosis.

Poor microcirculatory flow dynamics are associated with endothelial cell damage and glycocalyx shedding after traumatic hemorrhagic shock.

BACKGROUND: Endothelial cell damage and glycocalyx shedding after trauma can increase the risk of inflammation, coagulopathy, vascular permeability, and death. Bedside sublingual video-microscopy may detect worse flow and perfusion associated with this endotheliopathy. We compared markers of endotheliopathy with physical flow dynamics after traumatic hemorrhagic shock. METHODS: Sublingual incident dark field video-microscopy was performed at three time points after injury (<10 hours, 10-30 hours, and 30-50 hours). Values for microcirculatory flow index (MFI), Point Of carE Microcirculation assessment (POEM) score, proportion of perfused vessels (PPV), microcirculatory heterogeneity index (MHI), perfused vessel density (PVD), and total vessel density (TVD) were obtained. ELISAs were performed to measure concentrations of thrombomodulin and syndecan-1 as biomarkers of endothelial cell damage and glycocalyx shedding respectively. Flow parameters were dichotomized to above and below average, and biomarkers compared between groups; below average MFI, POEM, PPV, PVD, and TVD, and above average MHI were considered poor microcirculatory flow dynamics. RESULTS: A total of 155 sublingual video-microscopy clips corresponding to 39 time points from 17 trauma patients were analyzed. Median age was 35 (IQR 25-52); 16/17 were men. Within 10 hours of injury, syndecan-1 concentrations were significantly higher compared to 17 age- and sex-matched healthy controls (30 [IQR 20-44] ng/mL) for worse TVD (78 [IQR 63-417] ng/mL), PVD (156 [IQR 63-590] ng/mL), PPV (249 [IQR 64-578] ng/mL), MFI (249 [IQR 64-578] ng/mL), MHI (45 [IQR] 38-68) ng/mL), and POEM scores (108 [IQR 44-462] ng/mL) (all p < 0.01). Thrombomodulin was also raised within 10 hours of injury when compared to healthy controls (2.9 [IQR 2.2-3.4] ng/mL) for worse PPV (4.1 [IQR 3.4-6.2] ng/mL) and MFI (4.1 [IQR 3.4-6.2] ng/mL) (both p < 0.05). CONCLUSIONS: Endothelial cell damage and glycocalyx shedding are associated with worse flow, density, and heterogeneity within microvessels after traumatic hemorrhagic shock. The clinical utility of these biomarkers and flow parameters at the bedside are yet to be elucidated. LEVEL OF EVIDENCE: Prognostic study, level III.

Relationship between disruption of the unstirred mucus layer and intestinal restitution in loss of gut barrier function after trauma hemorrhagic shock.

BACKGROUND: The factors involved in shock-induced loss of gut barrier function remain to be defined fully and studies investigating gut injury have focused primarily on the systemic side of the intestine. METHODS: Male Sprague-Dawley rats were subjected to a laparotomy (trauma) and 90 minutes of trauma sham shock (T/SS) or actual trauma (laparotomy) hemorrhagic shock (T/HS) (30 mm Hg). At 0, 30, 60, or 180 minutes after the end of shock and volume resuscitation (reperfusion), the animals were killed and samples of the ileum were collected for intestinal morphologic analysis, analysis of the unstirred mucus layer, and for barrier function by measuring permeability to flourescein dextran. RESULTS: T/HS-induced morphologic evidence of mucosal injury as well as epithelial apoptosis was present at the end of the shock period and maximal after 60 minutes of reperfusion. At 3 hours after reperfusion, the degree of villous injury and enterocyte apoptosis had decreased. In contrast to the morphologic appearance of the villi, disruption of the mucus layer became progressively more severe over time and was manifest as a decrease in mucus thickness, progressive loss of coverage of the luminal surface by the mucus layer, and a change in mucus appearance from a dense to a loose structure. Studies of intestinal permeability documented that T/HS-induced loss of gut barrier function persisted throughout the 3-hour reperfusion period and were associated with injury to the mucus layer as well as the villi. CONCLUSIONS: T/HS leads to changes in the intestinal mucus layer as well as increased villous injury, apoptosis, and gut permeability. Additionally, increased gut permeability was associated with loss of the intestinal mucus layer suggesting that T/HS-induced injury to the mucus layer may contribute to the loss of gut barrier function.

[Effect of methylene blue on traumatic shock in rabbits].

OBJECTIVE: To observe the effect of methylene blue (MB) on the changes in plasma nitric oxide (NO), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and visceral pathologic changes in rabbits with traumatic shock. METHODS: Eighteen rabbits were randomly assigned into 3 groups (n=6): sham operation group, traumatic shock with normal saline (NS) resuscitation group (NS group), and traumatic shock with MB resuscitation group (MB group). In NS group and MB group, hemodynamics was monitored, and plasma contents of NO, TNF-alpha and IL-6 were determined before shock, after shock, after resuscitation, and 0.5, 2 and 4 hours after resuscitation. In sham operation control group, hemodynamics monitoring and plasma contents of NO, TNF-alpha and IL-6 were also determined. Tissue samples of the liver and intestine were obtained after experiments for microscopic examination. RESULTS: Compared with NS group, hemodynamics was stable in MB group. The levels of plasma NO in rabbits after traumatic shock were much higher than those of before shock. In NS group, the levels of plasma NO were progressively increased after resuscitation, reaching peak level at 0.5 hour after resuscitation, then decreased thereafter but still remaining higher than those of before shock. But in MB group, the levels of plasma NO after resuscitation were obviously decreased. In sham operation group, the levels of plasma NO showed no significant changes during the whole course. The levels of plasma TNF-alpha and IL-6 in rabbits after traumatic shock were much higher than those of before shock. But after intravenous administration of MB, the levels of plasma TNF-alpha and IL-6 after resuscitation showed no significant difference compared with the baseline levels. In sham operation group, the levels of plasma TNF-alpha and IL-6 showed no significant changes during the entire course. In NS group, the organs showed prominent pathologic changes. But in MB group, less pathologic changes in the organs were milder, and in sham operation group, there was no obvious pathologic changes in the organs. CONCLUSION: NO, TNF-alpha and IL-6 play important roles in the pathologic process of traumatic shock and the administration of MB after resuscitation can decrease the levels of plasma NO, TNF-alpha and IL-6, improve hemodynamics in traumatic shock, and protect the important organs.

Large animal models: baboons for trauma, shock, and sepsis studies.

A few limited examples of large animal models are outlined, with the main emphasis on baboon models. The baboon offers all the advantages of a large animal and is comparable with humans in nearly all physiological and immunological aspects. In addition, cross-reactivity with human therapeutic and diagnostic reagents allows testing of new species-specific therapies such as antihuman antibodies, on the one hand, and monitoring with available human analytical procedures, on the other.

[Protective effects of ulinastatin on ischemia/reperfusion injury in the rabbit lung in traumatic hemorrhagic shock].

OBJECTIVE: To investigate the effects and mechanisms of ulinastatin on activities of myeloperoxidase (MPO) in lung tissue and neutrophil elastase (NE) in bronchoalveolar lavage fluid and to evaluate the protective effects of ulinastatin on rabbit lung in traumatic hemorrhagic shock. METHODS: Thirty rabbits were randomly assigned to three groups: control group, traumatic hemorrhagic shock group and ulinastatin-treatment group. The traumatic hemorrhagic shock model was reproduced by producing: femur fracture and femoral artery bleeding to reduce the mean artery pressure to (40+/-5) mmHg (1 mmHg=0.133 kPa). The hypotension was maintained 90 minutes before the shed blood and equivalent amount of Ringer's lactate was infused. Four hours after blood volume compensation, the activities of MPO in lung tissue and NE in bronchoalveolar lavage fluid (BALF) were measured, and the extravascular lung water volume was determined. RESULTS: Compared with control group, the activities of either MPO in lung tissue or NE in BALF appeared to be increased in the ulinastatin-treatment group (both P<0.05), but their levels were significantly higher in traumatic hemorrhagic shock group(both P<0.05). The extravascular lung water volume was increased significantly in the two experimental group (both P<0.05), however it was more pronounced in traumatic hemorrhagic shock group (all P<0.05). CONCLUSION: Ulinastatin can inhibit the increase in the activities of MPO in lung tissue and NE in BALF, and possesses potential protective effects on the lung tissue in traumatic hemorrhagic shock.

Increased plasma D-lactate is associated with the severity of hemorrhagic/traumatic shock in rats.

D-lactate is produced by indigenous bacteria in the gastrointestinal tract. Mammals do not have the enzyme systems to metabolize D-lactate rapidly. The present study was designed to determine the kinetics of circulating D-lactate levels and to examine whether the severity of shock affects circulating D-lactate levels in rats subjected to hemorrhagic/traumatic shock. Anesthetized rats underwent midline laparotomy (duration 30 min) and were bled to 30-35 mmHg mean arterial pressure (MAP). After the onset of decompensation, MAP was either increased to 40-45 mmHg immediately by administration of Ringer's solution (moderate shock) or after 40% of shed blood volume had been re-infused as Ringer's solution (severe shock). MAP was then maintained at 40-45 mmHg for 40 min by further administration of Ringer's solution (inadequate resuscitation). Subsequently, adequate resuscitation was performed for 60 min with shed blood and additional Ringer's solution. Metabolic acidosis was significantly more pronounced in severe than in moderate hemorrhagic/traumatic shock. Plasma D-lactate levels were already significantly increased at the end of severe hemorrhagic/traumatic shock and remained high during inadequate resuscitation. D-lactate levels were significantly higher after severe than after moderate shock. Endotoxin levels did not correlate with shock severity. Damage to the intestinal mucosa was more profound in severe shock than in moderate shock. Our data suggest that hemorrhagic/traumatic shock is associated with mucosal damage and increased plasma D-lactate levels. The severity of shock affects D-lactate concentrations in plasma. Plasma D-lactate may be a useful marker of intestinal injury after hemorrhagic/traumatic shock.

Major burn trauma in rats promotes cardiac and gastrointestinal apoptosis.

The hypothesis that cardiac functional abnormalities that occur after major burn trauma are paralleled by an increased incidence of apoptosis in cardiac myocytes was examined. Adult Sprague-Dawley rats were given a full thickness scald burn comprising 43+/-1% of the total body surface area or were manipulated identically but not exposed to burn injury (sham burn); burned rats were fluid resuscitated with lactated Ringer's solution. Tissues from burn and sham burn animals were then examined by the TUNEL (TdT-mediated dUTP nick end labeling) assay and light microscopy to determine the presence of apoptosis 24 and 48 h after burn trauma. In parallel, the mechanical function of the heart was assayed in separate groups of rats. Tissues harvested from the hearts of sham-treated animals showed essentially no apoptosis, whereas a small number of apoptotic cells were noted in the intestinal villi and liver of sham-treated animals. Twenty-four hours after burn trauma, there was a marked increase in apoptotic cells in the left ventricle (+916%), and the number of apoptotic cells remained increased by eightfold 48 h postburn. Apoptosis was noted predominately in the subendocardial tissue of the left ventricle. The appearance of apoptotic cells was paralleled by a decrease in cardiac mechanical function with significant decreases in left ventricular pressure and +/-dP/dt(max). Burn injury also increased apoptosis in the small intestine significantly, whereas apoptosis in the liver did not increase with burn trauma. These data suggest that the apoptosis of the cardiac myocytes that occurs after burn trauma may contribute, in part, to postburn cardiac mechanical dysfunction.

L-arginine attenuates endothelial dysfunction and prolongs survival in rats subjected to traumatic shock.

We investigated the effects of L-arginine administration in a rat model of traumatic shock. Pentobarbital-anesthetized rats subjected to drum trauma developed a severe shock condition characterized by marked hypotension to 55-70 mmHg, a survival time of only 90 +/- 21 min, and significant increases in ileal myeloperoxidase (MPO) activity (P < 0.01). In addition, superior mesenteric artery (SMA) rings isolated from rats subjected to traumatic shock relaxed to the endothelium-dependent vasodilator acetylcholine significantly less than rings isolated from control rats (p < 0.01). Administration of L-arginine (30 mg/kg bolus + 10 mg/kg/hr, i.v.) 10 min following trauma prolonged survival time to 213 +/- 33 min (p < 0.05) and attenuated ileal MPO activity (p < 0.01) indicative of reduced neutrophil infiltration. Furthermore, SMA endothelial function was significantly (p < 0.01) preserved in L-arginine treated traumatic shock rats. These results indicate that L-arginine plays a key role in the endothelial dysfunction associated with traumatic shock and affords significant protective effects which may be manifested by an inhibition of leukocyte-endothelial cell interactions.

Whole-body inflammation in trauma patients. An autopsy study.

In a review of autopsy specimens and reports in 35 trauma cases, we found signs of generalized inflammation and tissue damage with increases in organ weights in organs not primarily injured. These abnormalities occurred independent of the time of death and were also found in patients who died of brain injury alone. The most pronounced signs of inflammation and increases in organ weights were found when the adult respiratory distress syndrome, hypovolemic shock, or multiple organ failure were the causes of death. These findings are similar to those found in several organs of rabbits after four hours of complement activation in combination with 20 minutes of hypoxia. Therefore, the autopsy findings in this series of trauma patients might represent the morphologic features of adult respiratory distress syndrome and multiple organ failure in an early, preclinical stage.