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Introduction: Despite advances in the surgical therapy of aortic injury (AI) using endovascular prostheses, more than 60% of motor vehicle crash (MVC) induced AIs die at the scene. In 80 cases of MVC AI, both change in velocity on impact (Delta V) and impact energy (IE) were correlated with autopsy or surgical findings. Of the 34 AIs due to lateral impact MVCs (LMVC), 91% had an aortic isthmus laceration. Computer simulation is used to study the cause of LMVC AI., Methods: To delineate AI mechanism, 10 real life LMVCs (8 left, 2 right) were simulated using a computer-based finite element numerical model. Each began with the initial vehicle impact with another vehicle or fixed object, followed by the vehicle's compartment structures' impact with the patient's chest wall, causing a rise in intra-aortic pressure and the resulting location and pattern of aortic wall stresses and strains. In the real LMVCs, the Delta V ranged from 27.5 to 62 kph with impact energies of from 46,051 to 313,502 joules. In both real-life and the model, the main cause of the chest wall impact was intrusion of the car's B-pillar. Dynamic simulations delineate increased stress and strains at the aortic Isthmus. In some LMVCs, the B-pillar intrusion was also seen to impact the head in the AI cases., Results: In the simulations, aortic pressure rose from 100 mm Hg precrash to as high as 1,322 mm Hg. Both the maximum aortic longitudinal tensile strain and the von Mises Stress were proportional to the maximum force impacted on the chest wall. Aortic isthmus maximum stresses ranged from 1.1 Mega Pascal (MPa) to 3.2 MPa, with longitudinal tensile strains ranging from 8.2% to 48.5%. The simulation dynamics demonstrated that the proximal pressurized turgid aorta initially moves toward the LMVC impact. As a result, the ascending aorta and aortic arch (proximal ascending aorta) rotate about the fulcrum of the great vessels, so that this aortic unit, acting as the long-arm of an Archimedes lever system, exerts the maximum stress and strain at the aortic isthmus or short-arm, where the real-life aortic rupture occurs., Conclusion: Simulation supports the lever hypothesis that the force on the short-arm aortic isthmus is proportionally greater than at the long-arm proximal aorta. Simulation also suggests improved vehicle construction techniques, which increase the strength and resistance to deformation of the B-pillar and vehicle side structure plus a B-pillar airbag will limit the intrusion forces causing LMVC AIs and reduce the incidence of associated head injuries.

This study was performed to obtain a characterization of the changes in plasma transferrin (Tf, g/L) in sepsis. More than four hundred determinations of Tf, and of a large series of simultaneously collected blood and hemodynamic variables, were obtained in 17 patients with post-traumatic sepsis. Tf during sepsis was consistently low (mean +/- SD = 1.46 +/- 0.46) however fluctuated markedly according to changes in metabolic and hemodynamic patterns. Regression analysis showed that decreases in Tf were simultaneously correlated with the plasma lipid pattern (in particular with decreasing cholesterol and increasing triglycerides), with decreases in albumin and peripheral O2 extraction, and with increasing cardiac index (p < 0.001 for all). Decreases in Tf were moderated by increasing the parenteral amino acid dose (p < 0.001). Combinations of these variables in multiple regressions explained nearly 80% of the variability of Tf. There were no similar correlations for other acute phase proteins except ceruloplasmin, which showed opposite changes compared to those of Tf. These results show that within the hypotransferrinemia which characterizes sepsis, Tf may oscillate remaining strongly correlated with changes in metabolic and hemodynamic patterns, which may account for nearly 80% of the variability of Tf.

Objectives: Can aortic isthmus disruption occurring in a lateral motor vehicle crash (LMVC) be explained by the Archimedes Lever Hypothesis, where the intrathoracic aorta, super-pressurized by the thoracic impact force, functions as a rigid lever system? The long arm of this lever system is the proximal aorta-aortic arch, the short arm is the aortic isthmus fixed distally at the descending aorta, and the fulcrum is at the great vessels, especially the left subclavian artery., Methods: The theory was tested by a simulation technique using a computer-based finite element numerical model system. This simulation model included the dynamics of the crashed vehicles, the direction of force impact, and the structure of the thorax and intrathoracic viscera, including the entire intrathoracic aorta. The specific patient whose data were entered into the model was chosen from a study of 34 LMCV aortic injuries (AIs). The model was constrained by patient and vehicle data from this surviving case., Results: Three sequential lateral thoracic levels impacted by the vehicle side structures were selected. At each level, the maximum mean intra-aortic pressure was 50 to 100 ms after impact, the structure dynamics of the actual crash and the resultant vehicle deformation were simulated; only when the lateral impact was induced in a transverse plane including the first 4 ribs at the level of the aortic arch/isthmus system, with intra-aortic pressures from 200 to 500 mm Hg, were AI-compatible stresses and deformations in the aortic wall achieved at the isthmus., Conclusions: In LMVC AI, the simulation suggests that the aorta functions as an Archimedes Lever System in which the magnified force mediated by the long lever arm produces sufficient strain on the short lever arm to rupture the aorta at the isthmus.

Evidence is increasing that oxygen debt and its metabolic correlates are important quantifiers of the severity of hemorrhagic and post-traumatic shock and and may serve as useful guides in the treatment of these conditions. The aim of this review is to demonstrate the similarity between experimental oxygen debt in animals and human hemorrhage/post-traumatic conditions, and to examine metabolic oxygen debt correlates, namely base deficit and lactate, as indices of shock severity and adequacy of volume resuscitation. Relevant studies in the medical literature were identified using Medline and Cochrane Library searches. Findings in both experimental animals (dog/pig) and humans suggest that oxygen debt or its metabolic correlates may be more useful quantifiers of hemorrhagic shock than estimates of blood loss, volume replacement, blood pressure, or heart rate. This is evidenced by the oxygen debt/probability of death curves for the animals, and by the consistency of lethal dose (LD)25,50 points for base deficit across all three species. Quantifying human post-traumatic shock based on base deficit and adjusting for Glasgow Coma Scale score, prothrombin time, Injury Severity Score and age is demonstrated to be superior to anatomic injury severity alone or in combination with Trauma and Injury Severity Score. The data examined in this review indicate that estimates of oxygen debt and its metabolic correlates should be included in studies of experimental shock and in the management of patients suffering from hemorrhagic shock.

Objective: To examine the effect of change in velocity (DeltaV) and energy dissipation (IE) on impact, above and below the test levels for Federal MVC Safety Standards, on the incidence of spine fractures (SF), spinal cord injury (SCI)), SF mortality and the associated injury patterns in Frontal (F) and Lateral (L) MVCs. Comparison of 214 patients with SF or SCI with 938 patients who did not have SF or SCI., Methods: 1152 MVC adult drivers or front-seat passengers (701 F & 451 L) evaluated at 10 Level I CIREN study Trauma Centers together with vehicle and crash scene engineering reconstruction. Patient seat belt (SB) and/or airbag (AB) use correlated with clinical, or autopsy findings., Results: The relationship between DeltaV and IE rose exponentially as DeltaV increased. Of the 1152 patients, all with AIS> or =3 injuries, there were 214 patients with spine fractures of AIS > or =2. In FMVCs there were more SF patients with Cervical SF than in LMVCs (68F versus 64 L) and more Thoracic (35F versus 21L) and Lumbar (39F versus 16L) SF. However, the incidence of spinal cord injury was greatest in the Cervical SF (33%), compared with the Thoracic SF (18%), or Lumbar SF (2%). Most important, in FMVCs 49% of SF, 47% of SCI and 71% of the SF deaths (p < 0.05) occurred at > mean of 47.4 kph. In contrast, in LMVCs 51% of SF, 52% of SCI and 67% of the SF deaths occurred at DeltaV > mean of 35.3 kph. However, 80% of all deaths in SCI occurred in Cervical SF cases, in these 74% also had a brain injury. In contrast, the deaths in Thoracic SF were due to combinations of brain (45%), thorax (95%) or associated pelvic fracture injuries (50%). Airbag (AB), or Seat belt (SB) restraints appeared to protect FMVC SF patients from SCI at lower DeltaV, but 84% of Cervical SCI patients at DeltaV > 47 kph had AB protection and in a few cases the AB appeared responsible for the SCI. In contrast, 82% of Lumbar SF patients had SB, but in FMVCs where jackknifing due to backloading occurred, improper SB positioning may have contributed to the SF., Conclusions: The implication for SCI in both front seat drivers and passengers in either FMVC or LMVC crashes above their respective DeltaV means is that improved spine fracture protection is necessary at higher DeltaV levels. More effective safety systems to prevent Cervical SCIs should be developed using two-level frontal and side AB & SB+pretensioner devices, which protect against SF at DeltaV both at and 1SD above the FMVC (47 & 72 kph = 30 & 45 mph) and LMVC (35 & 54 kph =22 & 34 mph) means.

Objective: To examine the effect of change in velocity (MV) and energy dissipation (IE) on impact, above and below the test levels for federal motor vehicle crash (MVC) safety standards, on the incidence of aortic injury (AI) and its mortality and associated injury patterns in frontal (F) and lateral (L) MVCs. Comparison of 80 AI and 796 non-AI patients of AIS=3., Methods: Eight hundred seventy-six MVC adult drivers or front-seat passengers (552 F and 324 L) evaluated by 10 Level I CIREN study Trauma Centers together with vehicle and crash scene engineering reconstruction. Patient seatbelt and/or airbag use correlated with clinical or autopsy findings., Results: In AI, 63% of cases were dead at the scene and only 16% survived to leave hospital. The relation between IE dissipated in the MVC and the DeltaV on impact was exponential as DeltaV increased, but the rise in IE for a given DeltaV was greater in LMVC than in FMVC (p <0.05). A more rapid rise in IE/DeltaV occurred above the mean DeltaV of 48 +/- 19.7 kph (30 mph) in FMVC and above the mean DeltaV of 36 +/- 16.2 kph (23 mph) in LMVC. As DeltaV increased above these means, 65% of 46 FMVC aortic injuries (AIs) and 64% of 34 LMVC AIs occurred. In AI patients there was evidence of focusing of the point of IE impact on the upper chest with a higher incidence of rib1-4 fractures than in non-AI (p <0.01) and more brain, heart, lung and spleen injuries (p <0.01) consequent to lower seatbelt use (p <0.01), but LMVC also had more pelvic fx (p <0.05). Airbags + seatbelts in FMVC and seatbelts in LMVC reduced mortality (p <0.05) Comparison of AI incidence in three successive 4-year vehicle model year periods showed a progressive decrease as new safety devices were introduced (p < 0.05)., Conclusions: The implications for AI of the focused IE at the upper chest suggest a probable mechanism for MVC AI with the pressurized aortic arch acting as the long arm of a lever system with the fulcrum at the subclavian artery, producing maximum torsional strain at the short arm of the isthmus where 75% of the AIs occurred. AI mortality is also influenced by the associated injuries. To develop more effective safety systems to prevent AI, MVC safety testing with airbags and seatbelts should be carried out at DeltaVs of 1 SD above means for FMVC and LMVC.

An acute septic inflammatory response with access to the portal circulation was created in a rat model using an intra-abdominal abscess composed of a sterile agar pellet, or one contaminated with 102 Escherichia coli (E. coli) and 109 Bacteriodes fragilis (B. fragilis). After 3 days postimplantation, a well-formed intra-abdominal abscess occurred whose wall showed IL-6 DNA by PCR and IL-6 mRNA by in situ hybridization. Portal venous blood draining into the liver from the intra-abdominal abscess had increased levels of TNF-alpha, IL-1beta, and IL-6 in both sterile and septic groups compared with a control normal animal group. Increased levels of these cytokines were also found in suprahepatic inferior vena caval blood, but were correlated with the higher portal vein levels, suggesting a gradient from abscess wall to portal vein into the systemic circulation via the liver. Liver histology demonstrated sinusoidal congestion centering on the central vein, growing worse with progression from normal in control, to sterile, to septic. Similarly, the degree of intrahepatic myeloperoxidase-positive inflammatory cell infiltration and hepatocellular lipid deposition and apoptosis also increased from control, to sterile, to septic. Gene expression by in situ hybridization demonstrated a significant increase in IL-6 and fibrinogen mRNAs in cells surrounding the central vein in sterile and septic animals, being greatest in animals with sepsis, associated with an increased deposition of collagen in the central vein area, most prominent in the septic liver. The pericentral vein cells with IL-6 and fibrinogen mRNA increases paralleled the increases in cells containing IL-6 and fibrinogen mRNAs in the abscess walls of sterile and septic animals, respectively. The data suggest that an intra-abdominal abscess, especially when contaminated with gram-negative bacteria, induces mRNA-generated cytokine responses in the abscess wall that are related to increased portal venous levels of the inflammatory cytokines TNF-alpha, IL-1beta, and IL-6 perfusing the liver. These, in turn, induce localized production of IL-6 and fibrinogen mRNAs in cells at the central vein area with resultant outflow fibrosis and increased inflammatory cell sequestration within the liver lobular sinuses. This is associated with a generalized inflammatory response and intrahepatic portal sinusoid congestion. There is also increased hepatocellular lipid deposition and apoptosis. Thus, the cytokine production of the abscess wall itself appears to be a major mediator of the septic hepatic response.

Objective: To determine the effect of major trauma on the cytokine-producing activity of monocytes and CD4+ T cells in a homogeneous cohort of patients as well as to determine the relationship between monocyte and T-lymphocyte responses and clinical outcome., Settings: Surgical intensive care units of a trauma center and flow cytometry and experimental laboratories at a teaching hospital., Design: Prospective cohort clinical study with measurements of white cell cytokine-producing activity on days 2, 5, and 10 postinjury. The number of cytokine-producing CD14+ monocytes, CD4+, and CD8+ T cells were determined in whole blood using flow cytometry combined with the intracellular cytokine staining method. Basal and lipopolysaccharide-stimulated interleukin (IL)-12, tumor necrosis factor-alpha, IL-6, and IL-1alpha production by monocytes as well as basal and phorbol 12-myristate 13-acetate plus ionomycin-stimulated interferon-gamma, IL-4, and tumor necrosis factor-alpha production by T cells were determined on days 2, 5, and 10 postinjury and compared with similar measurements made in healthy control subjects., Patients: Twelve randomly selected black, male patients were enrolled in the study: mean injury severity score, 26; mean age, 35 yrs; mean Glasgow Coma Scale score, 13; systemic inflammatory response syndrome, 92%; sepsis, 42%; bronchial infection, 42%; and adult respiratory distress syndrome 25%., Main Results: After lipopolysaccharide stimulation, the number of IL-12-, tumor necrosis factor-alpha-, IL-1alpha-, and IL-6-producing CD14+ monocytes was 40% to 70% lower in trauma patients on postinjury days 2, 5, and 10 than in healthy control subjects. After phorbol 12-myristate 13-acetate stimulation, the number of IL-4-producing CD4+ cells increased three-fold in the trauma patients compared with healthy control subjects. In contrast, the number of interferon-gamma- or tumor necrosis factor-alpha-producing CD4+ and CD8+ T cells was not different between the patients and control subjects. The Th1/Th2 ratio was significantly lower in patients on all postinjury days than in the control subjects. A statistically significant inverse correlation was found between the number of IL-12-producing monocytes and IL-4-producing CD4+ T cells in trauma patients (p =.007, r2 =.47). This correlation was absent in control subjects. The degree of depressed capacity of monocyte IL-12 production on day 2 postinjury showed a statistically significant correlation with the development of adult respiratory distress syndrome, sepsis, or infections and also with the duration of systemic inflammatory response syndrome and sepsis., Conclusions: Major trauma results in an early and marked decrease in monocyte cytokine-producing activity. The trauma-induced depression in IL-12 production by the mononuclear phagocyte system may promote T-cell commitment toward a Th2 pattern early after trauma. The appearance of the Th2 pattern is the result of elevated numbers of IL-4-producing cells without major alterations in T-cell interferon-gamma-producing capacity. The degree of alterations in monocyte and T-cell responses on day 2 postinjury correlates with the development of adverse clinical outcomes and the subsequent duration of the inflammatory response.

Background: The effectiveness of partial resuscitation after hypovolemic hemorrhagic shock with deferment of full resuscitation is critical to successful hypotensive resuscitation., Methods: To quantitatively address this issue, 40 canines were bled under anesthesia to a mean oxygen debt (O(2)D) of 104 +/- 7.6 mL/kg over 60 minutes (mortality, 40%). Animals surviving the shock were then immediately resuscitated with 0%, 8.4%, 15%, 30%, or 120% (full resuscitation) of shed volume as 5% albumin and held for 2 hours postshock, when the remaining portion of full resuscitation volume was given. Animals were followed for 7 days postshock with hepatic and renal function studies, and then, under anesthesia, cardiac output and organ biopsy specimens were taken before the animals were killed., Results: By 2 hours postshock, 0% immediate resuscitation had an O(2)D increase of 80 mL/kg above end of shock, but O(2)D at 8.4% immediate resuscitation decreased -30 mL/kg, 15% immediate resuscitation fell -65 mL/kg, 30% immediate resuscitation decreased -80 mL/kg below end of shock, and O(2)D with 120% full resuscitation fell to preshock levels. All decreases in O(2)D were significantly (p < 0.05) below end of shock, but both 15% and 30% immediate resuscitation exceeded the 8.4% immediate resuscitation rate (p < 0.05) throughout the resuscitation, and 120% full resuscitation exceeded these (p < 0.05). The immediate resuscitation O(2)D response correlated significantly (p < 0.001) with base deficit and lactate, but blood pressure was not a significant discriminator. Seven-day biopsies showed return of bowel mucosa but a pattern of cellular injury in heart, liver, and kidney that improved from 8.4% < 15% < 30 < 120% immediate resuscitation., Conclusion: The data suggest that, compared with 120% postshock immediate resuscitation, 8.4% and 15% immediate resuscitation give poorer results, with 30% immediate resuscitation showing mild, transient, but acceptable changes in organ function allowing for a 2-hour delay until full resuscitation, with complete 7-day recovery. Base deficit and lactate, but not blood pressure, are significant indices of O(2)D.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is one of the world's most common known human genetic polymorphisms, but the pathophysiology of the defect remains largely unknown. In the present study, we compared hematology parameters and ex vivo monocyte cytokine responses in non-deficient and G6PD-deficient trauma patients. Deficient and non-deficient, moderately injured, trauma patients exhibited similar hematology profiles at the time of hospital admission. In contrast to non-deficient patients, G6PD-deficient patients were anemic 2 days post-injury. Monocytes from deficient individuals produced 50% less interleukin 10 (IL-10) in response to LPS and >90% less IL-10 in response to PMA, compared with non-deficient patients, 2 days post-injury. The presence of phenylhydrazine-treated, opsonized, autologous RBC (OX-RBC), alone had no effect on IL-10 production by non-deficient or deficient monocytes, whereas IL-10 responses to lipopolysaccharide (LPS) were augmented by OX-RBC in both groups. However, IL-10 production was markedly lower by monocytes from G6PD-deficient than non-deficient patients after stimulation with LPS plus OX-RBC. TNF-alpha production following PMA was similar in deficient and non-deficient patients, and the differences following LPS or LPS plus OX-RBC stimulation were moderate between deficient and non-deficient samples. Interferon (IFN)-gamma production ex vivo was doubled by OX-RBC treatment alone, but it was not stimulated by LPS treatment. IFN-gamma production was similar in non-deficient and G6PD-deficient patients. These data suggest that the observed differences in IL-10 responses between G6PD-deficient and non-deficient patients are not attributable to differences in TNF-alpha or IFN-gamma production. Taken together, our data suggest that a reduction in the capacity to produce IL-10 may be an intrinsic characteristic of G6PD-deficient monocytes. An attenuated IL-10 production may be a contributing mechanism in the previously observed augmented inflammatory response in severely injured G6PD-deficient compared with non-deficient trauma patients.

Objective: To examine the difference in force mechanisms between fatal and potentially survivable MVC aortic injuries (AI) compared to non-AI severe thoracic injuries (ST)., Methods: Of 324 autopsied MVC driver or front seat passenger fatalities (1997-2000), there were 43 fatal AI (36 scene deaths, 7 hospital deaths) and 5 additional AI survivors., Results: Of the 48 AI, there was only a 42% survival for those reaching hospital alive. 80% of AI survivors had isthmus lesions and all had no or minimal brain injury (GCS >= 13), no cardiac injury and only 20% ribs 1-4 fx or shock; of AI non-survivors reaching hospital alive, 67% had GCS <= 12, 50% cardiac injury, 83% ribs 1-4 fx and 83% shock; AI scene deaths had 78% severe brain injury, 56% cardiac injury, 69% lung injury and 78% ribs 1-4 fx. Quantifying forces in AI scene mortality: the Instantaneous Velocity on Impact of the subject vehicle (delta V1) and the Impact Energy Dissipated (IE) on the subject vehicle (V1) in joules demonstrated a linear regression in fatal car MVC AIs: Energy dissipated (joules) = -56.65 x (delta V1)(2) + 15972 x delta V1 - 454661, r(2) = 0.83. However, for 27 patients with non-AI but severe thoracic (ST) injury (AIS>=3), the relationship of IE to delta V1 had a linear regression of Energy dissipated (joules) = -5.0787 x (delta V1)(2) + 4282.1 x delta V1 - 57182 1, r(2) = 0.84, with the slope difference between the regression for AI scene deaths and that of ST and AI survivors being significant (p<0.05). Based on these relationships, a Critical Zone limited by MVC Impact Energy level of 336000 joules and a delta V1 of 64 kph appears to be the limit of potential survivability in MVCs producing aortic injuries. All AI above these thresholds died. In contrast, ST had greater use of seatbelts (AI 10% vs all ST 60%) and airbags (AI 50% vs all ST 72%), and an 83% survival., Conclusion: The data suggest different mechanisms of force delivery and injury patterns in fatal vs potentially survivable AI, and vs ST MVCs. They suggest that an approach to improving vehicle safety measures for AI may involve better safety devices and mechanisms for reducing that fraction of Impact Energy dissipated on V1 for a given delta V1 which is focused on the upper portion of the subject's thoracic cage between the levels of ribs1-8.