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David N Herndon

Publications and source records attributed to David N Herndon.

At least 19 recordsLinked to original sources
PubMed2016

Early leukocyte gene expression associated with age, burn size, and inhalation injury in severely burned adults.

BACKGROUND: In the patient with burn injury, older age, larger percentage of total body surface area (TBS) burned, and inhalation injury are established risk factors for death, which typically results from multisystem organ failure and sepsis, implicating burn-induced immune dysregulation as a contributory mechanism. We sought to identify early transcriptomic changes in circulating leukocytes underlying increased mortality associated with these three risk factors. METHODS: We performed a retrospective analysis of the Glue Grant database. From 2003 to 2010, 324 adults with 20% or greater TBS burned were prospectively enrolled at five US burn centers, and 112 provided blood samples within 1 week after burn. RNA was extracted from pooled leukocytes for hybridization onto Affymetrix HU133 Plus 2.0 GeneChips. A multivariate regression model was constructed to determine risk factors for mortality. Testing for differential gene association associated with age, burn size, and inhalation injury was based on linear models using a fold change threshold of 1.5 and false discovery rate of 0.05. RESULTS: After adjusting for potential confounders, age greater than 60 years (relative risk [RR], 4.53; 95% confidence interval [CI], 2.93-6.99), burn size greater than 40% TBS (RR, 4.24; 95% CI, 2.61-6.91), and inhalation injury (RR, 2.08; 95% CI, 1.35-3.21) were independently associated with mortality. No genes were differentially expressed in association with age greater than 60 years or inhalation injury. Fifty-one probe sets representing 39 unique genes were differentially expressed in leukocytes from patients with burn size greater than 40% TBS; these genes were associated with platelet activation and degranulation/exocytosis, and gene-set enrichment analysis suggested increased cellular proliferation and down-regulation of proinflammatory cytokines. CONCLUSION: Among adults with large burns, older age, increasing burn size, and inhalation injury have a modest effect on the leukocyte transcriptome in the context of the "genomic storm" induced by a 20% or greater than TBS burned. The 39-gene signature we identified may provide novel targets for the development of therapies to reduce morbidity and mortality associated with burns greater than 40% TBS. LEVEL OF EVIDENCE: Epidemiologic study, level III.

Adult↗
PubMed2007

Respiratory management of inhalation injury.

Advances in the care of patients with major burns have led to a reduction in mortality and a change in the cause of their death. Burn shock, which accounted for almost 20 percent of burn deaths in the 1930s and 1940s, is now treated with early, vigorous fluid resuscitation and is only rarely a cause of death. Burn wound sepsis, which emerged as the primary cause of mortality once burn shock decreased in importance, has been brought under control with the use of topical antibiotics and aggressive surgical debridement. Inhalation injury has now become the most frequent cause of death in burn patients. Although mortality from smoke inhalation alone is low (0-11 percent), smoke inhalation in combination with cutaneous burns is fatal in 30 to 90 percent of patients. It has been recently reported that the presence of inhalation injury increases burn mortality by 20 percent and that inhalation injury predisposes to pneumonia. Pneumonia has been shown to independently increase burn mortality by 40 percent, and the combination of inhalation injury and pneumonia leads to a 60 percent increase in deaths. Children and the elderly are especially prone to pneumonia due to a limited physiologic reserve. It is imperative that a well organized, protocol driven approach to respiratory care of inhalation injury be utilized so that improvements can be made and the morbidity and mortality associated with inhalation injury be reduced.

Bronchoscopy↗
PubMed2007

Blood transfusions are associated with increased risk for development of sepsis in severely burned pediatric patients.

OBJECTIVE: To determine the risk of developing sepsis following transfusion of blood products in severely burned pediatric patients. DESIGN: Retrospective, cohort study. SETTING: Shriners Hospital for Children and University Hospital. PATIENTS: Severely burned pediatric patients with >30% total body surface area (TBSA) burn. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Two hundred seventy-seven pediatric burn patients over a period of 7 yrs (1997-2004) were included in the study, with 25 patients being septic at admission and therefore excluded. Patients were stratified according to TBSA burn and presence or absence of inhalation injury. The amounts of packed red blood cells (RBCs) and fresh frozen plasma (FFP) were recorded during hospital stay before the development of sepsis. Blood product administration was normalized for the number of surgeries and divided into two groups: high (RBCs>20/FFP>5) or low (RBCs<20/FFP<5) amount of blood products. Sepsis was diagnosed based on the criteria set by the Society of Critical Care Medicine in conjunction with positive blood culture or presence of organisms in the organs at autopsy. By stratifying the groups into low and high blood transfusion, we found that patients with >60% TBSA burn with inhalation injury have an 8% risk of developing sepsis in the low RBC group, which increases to 58% in the high RBC group (p<.05). Similar results were found for RBCs per operation, FFP, and FFP per operation (p<.05). There were no differences in age and gender between groups. CONCLUSIONS: Pediatric burn suffering from a 60% TBSA burn with concomitant inhalation injury are more likely to develop sepsis if they are given high amounts of blood products, indicating an immunocompromised state following blood transfusion.

Burns↗
PubMed2007

Serum cytokine differences in severely burned children with and without sepsis.

The aim was to determine whether serum cytokine profiling early after burn can be used to identify patients at high risk of developing and subsequently dying of sepsis. A case series study was designed to determine whether serum cytokine profiling allows identification of patients at highest risk of developing and dying of sepsis at the time of hospital admission. All patients were treated according to the standard of burn care at our facility. Forty-four children (1-19 years old) with more than 40% of total body surface area and admitted within 7 days postburn were studied. None had infections or sepsis at the time of admission. Serum was collected before the first operation, and concentrations of 17 cytokines were measured. Diagnosis of sepsis was made at autopsy with identification of the pathogen. Fifteen patients developed sepsis and died, whereas 29 patients did not develop sepsis and survived. Significant elevations in serum interleukin (IL) 6, IL-8, IL-10, granulocyte-monocyte colony-stimulating factor, interferon gamma (IFN-gamma), tumor necrosis factor (TNF), and IL-12 p70 were found at the time of admission of patients who subsequently developed and died of sepsis when compared with burned patients who did not develop sepsis (P < 0.05). Multiple logistic regression analysis revealed that patients with a combination of elevated IL-6 and IL-12 p70 and lower TNF had an elevated risk of dying of sepsis. Serum IL-6, IL-8, IL-10, granulocyte-monocyte colony-stimulating factor, IFN-gamma, TNF, and IL-12 p70 are expressed differently in patients who die of sepsis versus those who never become septic. In addition, serum IL-6, IL-12 p70, and TNF can be used to identify burned patients who are at high risk of death from sepsis.

Burns↗
PubMed2007

Insulin attenuates the cytokine response in a burn wound infection model.

A massive burn is one of the most serious injuries resulting in major imbalances of the immune system. The aftermath of a burn is frequently complicated by infections and septic events that additionally increase mortality and morbidity. The aim of the present study was to investigate if insulin attenuates the cytokine response of burned mice challenged with Pseudomonas. Male mice (C57/BL/6) received a full thickness burn of 35% of their total body surface area. Mice received 5 IU/kg insulin i.p. or an equal volume of saline for 5 days after burn. Mice were challenged with 5x10 colony forming units Pseudomonas aeruginosa intraperitoneally. Serum was harvested 6 h after the bacterial challenge, and 18 serum cytokines were measured using the Bio-Plex suspension array system (Bio-Rad, Hercules, Calif). All 18 cytokines were elevated after the Pseudomonas challenge. However, mice treated with insulin showed significantly lower proinflammatory cytokine concentrations of interleukin 5, interleukin 6, and keratinocyte-derived chemokine after the Pseudomonas infection when compared with placebo-treated mice (P<0.05). In contrast, serum concentrations of G-CSF were significantly higher in insulin-treated animals when compared with placebo (P<0.05). We conclude, that insulin treatment selectively modulates specific cytokines in a burn wound infection model.

Animals↗
PubMed2006

The effects of oxandrolone and exercise on muscle mass and function in children with severe burns.

OBJECTIVES: Severe burns are associated with a significant loss of muscle and strength. Studies have reported that oxandrolone improves lean body mass in muscle-wasting conditions. Also shown previously in burned children is that an exercise program increases lean body mass and muscle strength. We hypothesized that oxandrolone, in combination with exercise, would increase lean body mass and muscle strength in severely burned children more than oxandrolone alone or exercise alone. METHODS AND PATIENTS: Fifty-one burned children (> or = 40% total body surface area burned) were randomly assigned to receive oxandrolone alone (0.1 mg/kg per day orally; n = 9), oxandrolone and exercise (n = 14), placebo and no exercise (n = 11), or placebo and exercise (n = 17). Administration of oxandrolone was started at discharge and continued until 1 year after burn. The 12-week exercise training program was started 6 months after burn. Serum hormones, lean body mass, muscle strength, and peak cardiopulmonary capacity were assessed at 6 (baseline) and 9 months after burn. Data were analyzed using a 1-way analysis of variance, and significance was set at P < .05. RESULTS: The mean percentage of change or increase in weight and lean body mass in the oxandrolone and exercise group was significant compared with placebo and exercise, as well as with the oxandrolone alone group or placebo and no exercise group. Furthermore, lean body mass was significantly improved in the oxandrolone and exercise, oxandrolone alone, and placebo and exercise group compared with the group only receiving placebo. Muscle strength significantly increased in oxandrolone and exercise, placebo and exercise, and the oxandrolone alone group when compared with the placebo and no exercise group. The peak cardiopulmonary capacity was significantly higher in both exercise groups. Insulin-like growth factor 1 was significantly increased in the oxandrolone alone group compared with placebo and exercise and placebo and no exercise. Both exercise groups showed significant changes in insulin-like binding-protein-3 when compared with groups without exercise. CONCLUSIONS: Oxandrolone, in combination with exercise, is beneficial in severely burned children, thus improving their rehabilitation.

Adolescent↗
PubMed2006

Glycyrrhizin inhibits the manifestations of anti-inflammatory responses that appear in association with systemic inflammatory response syndrome (SIRS)-like reactions.

In association with the systemic inflammatory response syndrome (SIRS), anti-inflammatory response syndrome is commonly manifested in patients with trauma, burn injury, and after major surgery. These patients are increasingly susceptible to infection with various pathogens due to the excessive release of anti-inflammatory cytokines from anti-inflammatory effector cells. Recently, CC-chemokine ligand 2 (CCL2) found in the sera of mice with pancreatitis was identified as an active molecule for SIRS-associated anti-inflammatory response manifestation. Also, the inhibitory activity of glycyrrhizin (GL) on CCL2 production was reported. Therefore, the effect of GL on SIRS-associated anti-inflammatory response manifestation was investigated in a murine SIRS model. Without any stimulation, splenic T cells from mice 5 days after SIRS induction produced cytokines associated with anti-inflammatory response manifestation. However, these cytokines were not produced by splenic T cells from SIRS mice previously treated with GL. In dual-chamber transwells, IL-4-producing cells were generated from normal T cells cultured with peripheral blood polymorphonuclear neutrophils (PMN) from SIRS mice. However, IL-4-producing cells were not generated from normal T cells in transwell cultures performed with PMN from GL-treated SIRS mice. CCL2 was produced by PMN from SIRS mice, while this chemokine was not demonstrated in cultures of PMN from SIRS mice treated with GL. These results indicate that GL has the capacity to suppress SIRS-associated anti-inflammatory response manifestation through the inhibition of CCL2 production by PMN.

Animals↗
PubMed2006

Gut mucosal homeostasis and cellular mediators after severe thermal trauma and the effect of insulin-like growth factor-I in combination with insulin-like growth factor binding protein-3.

Increased small bowel epithelial cell apoptosis and decreased cell proliferation lead to impairment of gut mucosal integrity and function after thermal injury. Impairment of gut integrity is associated with increased bacterial translocation and incidence of sepsis. The purpose of this study was to determine whether IGF-I/IGF binding protein (IGFBP)-3 can improve small bowel homeostasis after injury and by which cellular mechanisms these changes occur and to identify changes in apoptosis-related genes after burn and the effect of bile acid on small bowel epithelial cell apoptosis after burn. Rats sustained a thermal injury and received saline or the IGF-I/IGFBP-3 complex. Serum and small intestine were taken at 1, 2, 5, and 7 d after injury and serum inflammatory cytokines and mucosal apoptosis, proliferation, villous morphology, and apoptotic and proliferative mediators were measured. Apoptosis-related gene expression and the bile acid pool were determined in separate experiments up to 6 h after burn. Gut epithelial cell apoptosis as well as apoptosis-related genes were increased after the thermal injury, whereas bile acid secretion was significantly decreased (P < 0.05). IGF-I/IGFBP-3 significantly improved villous height and cells per villous by decreasing small bowel epithelial cell apoptosis and increasing proliferation (P < 0.05). Decreased apoptosis was associated with decreased Fas, Fas-ligand, and TNF when compared with saline (P < 0.05). A severe thermal injury caused an up-regulation of apoptosis and apoptosis-related genes and down-regulation of bile acid secretion. IGF-I/IGFBP-3 decreases small bowel epithelial cell apoptosis through down-regulation of the Fas pathway, which improves gut mucosal integrity after a severe thermal injury.

Animals↗
PubMed2006

Immunohistochemical staining of transgenic beta-galactosidase in burned skin is a better indicator of transfection efficiency than histochemical techniques.

The non-mammalian reporter gene LacZ, encoding the protein beta-galactosidase (beta-Gal), has long been used to test the efficiency of gene transfer into cells in culture or tissues in vivo. Biodistribution and dose-response transfection experiments rely upon a sensitive and specific technique for accurate results. We conducted an experiment to compare two techniques of identifying beta-galactosidase expression. The presence of beta-Gal was detected by dual staining transfected murine skin by both immunohistochemical (alkaline phosphatase) as well as histochemical staining (5-bromo-indolyl-beta-o-galactopyranoside [Bluo-Gal]). We demonstrated an almost two-fold increase in beta-galactosidase transfected dermal cell staining using immunohistochemistry as compared with histochemical staining. This translates to nearly 63% cells that were transfected with LacZ but were not identified by Bluo-Gal. The superior sensitivity of immunostaining suggests that anti-beta-Gal antibody represents the preferred analytical tool for light microscopic evaluation of LacZ gene transfer, promoter analysis in transgenic animals. Thus, identification of activity as opposed to presence of the enzyme underestimates gene expression following LacZ gene transfer in skin.

Animals↗
PubMed2006

Production of pro-inflammatory polypeptides by airway mucous glands and its potential significance.

Burn patients often develop respiratory distress and ARDS several days after injury. An ovine model allows experimental study of this problem. In sheep the injury is characterized by intense acute inflammation in the trachea and bronchi from 3 to 48h after injury, with accumulation of neutrophils, fibrin and other plasma proteins, and mucus in airway lumens. We have carried out immunostaining for multiple cytokines in this model, including interleukin-8 (IL-8), Interleukin-1 beta (IL-1beta), interleukin-1 alpha (IL-1alpha), tumor necrosis factor-alpha (TNF-alpha), and vascular endothelial growth factor (VEGF). All of these show intense immunostaining in airway mucous glands. IL-1beta and VEGF show substantial constitutive staining in the serous cells of mucous glands, while IL-8, IL-1alpha, and TNF-alpha show substantially increased expression after injury. This pattern of expression of cytokines in mucous glands, and the apparent release of cytokines into the lumen after injury, are considered potentially highly significant in the progression of injury in this model. In addition, a proinflammatory function of mucous glands might prove to be important in chronic lung diseases such as chronic bronchitis and asthma.

Animals↗
PubMed2006

Resting energy expenditure in severely burned children: analysis of agreement between indirect calorimetry and prediction equations using the Bland-Altman method.

INTRODUCTION: Knowledge of a child's resting energy expenditure (REE) is essential in optimizing nutritional support for severely burned children. The provision of adequate nutritional support is vital in order to avoid the consequences of malnutrition or overfeeding. Nutritional requirements for severely burned children are often based on equations for estimates of REE. The accuracy of the predictive equations of REE has been questioned and many authors have advocated the measurement of REE. This study tests the hypothesis that estimates of REE vary significantly from measured REE (MREE) in a population of severely burned children, and are not accurate for determining nutritional requirements. METHODS: In 91 severely burned children aged between 3 and 18 years, REE was measured by indirect calorimetry (MREE) at the height of the hypermetabolic response and compared with predicted equations (PREE) from the Food and Agriculture/World Health Organization/United Nations University (FAO/WHO/UNU), Schofield-HW and Harris-Benedict. Agreement between indirect calorimetry and predicted equations was assessed following the Bland-Altman method. RESULTS: In the entire cohort group, predicted REE from all three equations were significantly lower compared to MREE (p<0.05). There was poor agreement between the MREE and predicted using all three equations. The Schofield-HW equation showed the lowest mean MREE-PREE difference: 635+/-526 kcal/day (limits of agreement -608 and 1878 kcal/day; 95% confidence interval for the bias 525-745 kcal/day). Additionally, all three equations under predicted REE and were not significantly different from one another (p=0.98). CONCLUSIONS: Until more accurate predicted equations are developed, we recommend indirect calorimetry measurements for determining resting energy expenditure in severely burned children.

Adolescent↗
PubMed2006

CCL2 as a trigger of manifestations of compensatory anti-inflammatory response syndrome in mice with severe systemic inflammatory response syndrome.

Patients with compensatory anti-inflammatory response syndrome (CARS) are at a higher risk for infection with various opportunistic pathogens. CARS develops commonly in association with the manifestation of systemic inflammatory response syndrome (SIRS). In the present study, the role of SIRS-associated soluble factors on the CARS development was examined in mice with pancreatitis, a carrier of typical SIRS. Following the production of SIRS-related cytokines [tumor necrosis factor alpha and interleukin (IL)-1beta], CC chemokine ligand 2 (CCL2), IL-4, and IL-10 (typical CARS cytokines) were detected in the sera of mice with pancreatitis. CCL2 has been described as an essential chemokine for the T helper cell type 2 manifestation. CARS effector cells (cells with an ability to produce IL-4 and IL-10) were not generated from normal T cells after stimulation with SIRS-related cytokines. However, these cells were generated from normal T cells after cultivation with peripheral blood neutrophils (PMN) from SIRS mice in a dual-chamber transwell. Normal T cells did not convert to CARS effector cells after transwell cultures with PMN from normal mice. CCL2 was detected in culture fluids of PMN from SIRS mice, and PMN from normal mice did not produce CCL2 into their culture fluids. CARS effector cells did not appear in PMN-depleted SIRS mice or SIRS mice treated with anti-CCL2 monoclonal antibody, and these cells were demonstrated in PMN-depleted SIRS mice after treatment with recombinant murine CCL2. These results indicate that CCL2 produced by PMN from SIRS mice is an active molecule on the SIRS-associated CARS manifestation.

Animals↗
PubMed2006

Comparison of carbon monoxide (CO) single breath pulmonary diffusing capacity with non-rebreathing, open-circuit CO pulmonary diffusing capacity in healthy children.

INTRODUCTION: The standard technique for assessing pulmonary diffusing capacity of the lungs (DL) for carbon monoxide (CO) is the single breath (SB) technique. SB_DLco in children can be problematic because it requires a vital capacity >1.5 L. We have developed an open-circuit technique (OC), which uses the wash-in of CO over a series of 8-10 normal breaths that does not require rebreathing. In this study, we compared the SB_DLco against the OC_DLco. METHODS: Nineteen healthy children between 7 and 18 years performed SB_DLco and OC_DLco tests. The mean SB_DLco was significantly larger than the mean OC_DLco. The mean difference OC_DLco minus SB_ DLco was: -2.92 +/- 4.21 ml/min/mm Hg, though the difference was negatively correlated with the mean of the two (r = 0.73). The lower mean OC_DLco was in part due to lower lung volume (as measured by alveolar volume (VA)) during the maneuver. In both groups there was a positive correlation between VA and DLco, and the mean VA was -2.17 +/- 1.07 L lower using OC compared to SB. The difference was again negatively correlated with the mean (r = 0.82). The mean OC minus SB difference in DLco/VA was: 6.06 +/- 1.98 ml/min/mm Hg/L, though this difference was positively correlated with the mean, r = 0.76. CONCLUSIONS: We found a good correlation between both techniques for DLco, VA, and DLco/VA. The OC offers the advantage of minimal subject cooperation, and may be preferable to use in children.

Adolescent↗
PubMed2006

Continuous nebulized albuterol attenuates acute lung injury in an ovine model of combined burn and smoke inhalation.

OBJECTIVE: Albuterol, due to its bronchodilatory and anti-inflammatory effects, is given via continuous nebulization in children with severe asthma. Combined burn and smoke inhalation injury frequently results in acute lung injury due to a combination of airway obstruction and inflammation. We hypothesized that albuterol administered via continuous nebulization would mitigate acute lung injury after smoke inhalation injury and burn. DESIGN: Randomized prospective animal model. SUBJECTS: Twenty adult female sheep (mean weight, 33.1+/-0.9 kg). INTERVENTIONS: Adult ewes were subjected to a 40% body surface area third-degree flame burn and smoke inhalation injury after tracheostomy. Sheep were allocated to a) sham group, b) saline continuous nebulization group, c) 20 mg of albuterol continuous nebulization group, or d) 40 mg of albuterol continuous nebulization group (n=5 animals per group). All groups received intravenous lactated Ringer's solution at 4 mL.kg-1.%burn(-1).24 hrs-1 for resuscitation and were equally mechanically ventilated throughout the 48-hr study period. Pulmonary and cardiac function, lung lymph flow, bronchial obstruction score, and wet/dry lung weights were recorded. RESULTS: Compared with saline and control groups, the albuterol groups had lower pause and peak inspiratory pressures, decreased pulmonary transvascular fluid flux, a significantly higher Pao2/Fio2 ratio, and decreased shunt fraction at 48 hrs postinjury. The wet-to-dry lung weight ratio and bronchial obstruction scores were lower for sheep receiving albuterol. CONCLUSIONS: Continuous nebulization of albuterol improves pulmonary function via improved airway clearance and decreased fluid flux in a combined burn/smoke inhalation injury model.

Administration, Inhalation↗
PubMed2006

Recombinant human activated protein C improves pulmonary function in ovine acute lung injury resulting from smoke inhalation and sepsis.

OBJECTIVE: To investigate the effects of recombinant human activated protein C (rhAPC) on pulmonary function in acute lung injury (ALI) resulting from smoke inhalation in association with a bacterial challenge. DESIGN: Prospective, randomized, controlled, experimental animal study with repeated measurements. SETTING: Investigational intensive care unit at a university hospital. SUBJECTS: Eighteen sheep (37.2 +/- 1.0 kg) were operatively prepared and randomly allocated to either the sham, control, or rhAPC group (n = 6 each). After a tracheotomy had been performed, ALI was produced in the control and rhAPC group by insufflation of 4 sets of 12 breaths of cotton smoke. Then, a 30 mL suspension of live Pseudomonas aeruginosa bacteria (containing 2-5 x 10(11) colony forming units) was instilled into the lungs according to an established protocol. The sham group received only the vehicle, i.e., 4 sets of 12 breaths of room air and instillation of 30 mL normal saline. The sheep were studied in the awake state for 24 hrs and were ventilated with 100% oxygen. RhAPC (24 mug/kg/hr) was intravenously administered. The infusion was initiated 1 hr post-injury and lasted until the end of the experiment. The animals were resuscitated with Ringer's lactate solution to maintain constant pulmonary artery occlusion pressure. MEASUREMENTS AND MAIN RESULTS: In comparison with nontreatment in controls, the infusion of rhAPC significantly attenuated the fall in Pao2/Fio2 ratio (control group values were 521 +/- 22 at baseline [BL], 72 +/- 5 at 12 hrs, and 74 +/- 7 at 24 hrs, vs. rhAPC group values of 541 +/- 12 at BL, 151 +/- 29 at 12 hours [p < .05 vs. control], and 118 +/- 20 at 24 hrs), and significantly reduced the increase in pulmonary microvascular shunt fraction (Qs/Qt; control group at BL, 0.14 +/- 0.02, and at 24 hrs, 0.65 +/- 0.08; rhAPC group at BL, 0.24 +/- 0.04, and at 24 hrs, 0.45 +/- 0.02 [p < .05 vs. control]) and the increase in peak airway pressure (mbar; control group at BL, 20 +/- 1, and at 24 hrs, 36 +/- 4; rhAPC group at BL, 21 +/- 1, and at 24 hrs, 28 +/- 2 [p < .05 vs. control]). In addition, rhAPC limited the increase in lung 3-nitrotyrosine (after 24 hrs [%]: sham, 7 +/- 2; control, 17 +/- 1; rhAPC, 12 +/- 1 [p < .05 vs. control]), a reliable indicator of tissue injury. However, rhAPC failed to prevent lung edema formation. RhAPC-treated sheep showed no difference in activated clotting time or platelet count but exhibited less fibrin degradation products (1/6 animals) than did controls (4/6 animals). CONCLUSIONS: Recombinant human activated protein C attenuated ALI after smoke inhalation and bacterial challenge in sheep, without bleeding complications.

Airway Obstruction↗