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PubMed1992

The effect of burn wound size on hemostasis: a correlation of the hemostatic changes to the clinical state.

The effect of burn wound size on the activation of fibrinolysis, coagulation, and contact factors was analyzed in 60 thermal injury patients. Blood samples from 47 male patients and 13 female patients, (average age 37 years; range 1.5-70 years) were collected within the first 36 hours and at 5-7 days following injury. The patient population was categorized by percentage of burn (second degree and/or third degree): less than 20%, n = 22; 20%-40%, n = 18; greater than 40%, n = 20. The average percentage of burn was 32% (range, 4%-95%). The mechanism of injury was by flame (25), explosion and flame (19), scald (12), electric (3), or chemicals (1). An associated inhalation injury was present in 12 patients. The overall mortality rate was 13% (8). Sepsis or serious infection occurred in 23% (14) of the patients. On admission, 83% of the patients had normal prothrombin times (PT) and activated partial thromboplastin times (APTT). However, specific hemostatic variables showed marked changes. Admission hemostatic markers that correlated with the severity of injury were: tissue-plasminogen activator (tPA), plasminogen activator inhibitor (PAI), D-dimer (D-di), plasminogen (Plg), proteins C and S (PrC and PrS), antithrombin III (ATIII), thrombin-antithrombin complex (TAT), kallikrein (Kal:c), kinin (Kin), C1 esterase inhibitor (C1Inh), and factor VII clotting and antigen (FVII:c, FVII:ag). These data suggest that during the early course following burn injury, thrombogenicity is increased (TAT increases) because of a decrease in ATIII, PrC, and PrS; and fibrinolysis activation (D-di increases) occurs via an increase in tPA with a p value increase in PAI.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Noninvasive assessment of metabolism in wounded skin by 31P-NMR in vivo.

Phosphorus-31 nuclear magnetic resonance techniques using shallow penetrating coils have been used to noninvasively monitor severity and metabolic changes over time in skin wounds in rats. Ratios of phosphocreatine (PCr) to inorganic phosphate (Pi) indicate energy status in both thermal wounds and surgical flaps. In partial and full-thickness scald wounds, reductions in PCr/Pi ratios correlated with burn depth and improved over time postinjury, suggesting wound revascularization. No decrease in intracellular pH was noted in these wounds; the phosphate shifts may be primarily the result of tissue degradation followed by restoration of the microvasculature. Distal regions of caudally based dorsal 3 x 10 cm full-thickness skin flaps reveal progressively lower PCr/Pi ratios to 3-6 hours after elevation as well as drops in pH up to 0.5 units, presumably as a result of anaerobic glycolysis in these tissues. After 24 hours, the intracellular pH returned to normal (7.1-7.2) and the PCr/Pi ratios approached 70%-90% of the well-perfused proximal regions within 3-7 days. These results indicate the establishment of a microvasculature from the underlying bed as the distal regions survive as free grafts. The data demonstrate the potential usefulness of the technique in noninvasive measurement of the biochemical response to injury and wound healing in living organisms.

Animals↗
PubMed1994

Alpha-Trinositol inhibits edema generation and albumin extravasation in thermally injured skin.

Pharmacologic attempts to reduce edema generation and albumin extravasation into thermally injured skin have until recently been disappointing unless the drugs (usually antiphlogistic or anti-inflammatory drugs) were given before injury. We have studied the effect of alpha-trinositol (PP56, i.e., 1D-myo-inositol-1,2,6-trisphosphate) given after the injury in an experimental full-thickness 10% TBSA scald burn in anesthetized rats. Total tissue water content (TTW) and albumin extravasation (Ealb) were determined in injured and noninjured skin (series I, n = 12). Interstitial fluid hydrostatic pressure (Pif) was measured in injured skin (series II, n = 14). alpha-Trinositol was administered (alpha-trinositol groups) as an i.v. bolus (40 mg/kg) at 5 minutes after injury followed by an i.v. infusion (1.3 mg/kg/min). In both series a placebo group received burn injury and normal saline in equal volumes instead of alpha-trinositol. Compared with placebo, alpha-trinositol reduced TTW and Ealb as well as the increased negatively of Pif in injured tissue significantly. The effect on Ealb was most prominent, with a reduction from 153.9 +/- 35.6 (SEM) microL/g in the NaCl group to 23.1 +/- 6.3 after alpha-trinositol (p < 0.005). Total tissue water was reduced from 2.51 +/- 0.13 to 2.17 +/- 0.06 mL/g (p < 0.05) and Pif (measured between 21 and 40 minutes postinjury) from -24.7 +/- 4.1 to -3.2 +/- 1.1 mm Hg (p < 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Albumins↗
PubMed1994

Marrow granulocyte-macrophage progenitor cell response to burn injury as modified by endotoxin and indomethacin.

The production and release of granulocytes and macrophages are significantly impaired following burn injury and infection. In an attempt to determine the factors responsible for these adverse effects and their potential treatments, we performed a series of studies in mice analyzing the bone marrow response to burn wound infection. The proliferative response of the marrow granulocyte-macrophage progenitor cell (GM-CFC) in male BDF1 mice undergoing a dorsal scald burn or burn wound seeding with 1000 colony forming units of Pseudomonas aeruginosa was determined on day 3 postburn using a clonal culture of GM-CFC. Mice with infected burn wounds had a rate of GM-CFC proliferation that was 50% that of noninfected animals and levels of circulating colony stimulating activity (CSA) 30% those of controls (p = 0.006). Similar suppression of marrow proliferative status could be replicated with the administration of endotoxin to normal or burned animals as had been observed for burn-infected animals. The administration of indomethacin (5 mg/kg.day) substantially restored the GM-CFC proliferation in mice with infected burns as well as in animals given endotoxin. Indomethacin-treated animals had CSA values 244% those of untreated burn-infected animals (p = 0.016). We take these observations to suggest that suppression of myelopoiesis in burn-infected animals is related in part to endotoxin-stimulated production of prostaglandin mediators that altered myeloid proliferation and was responsive to cyclooxygenase blockade.

Animals↗
PubMed1995

Delayed hypertonic saline dextran administration after burn injury.

OBJECTIVE AND DESIGN: Experimental studies in our laboratory showed that hypertonic saline dextran (HSD; 7.5 NaCl in 6% dextran 70) given as a small bolus (4 mL/kg) immediately after burn injury in guinea pigs improved cardiac contractile performance and reduced the total fluids requirements. Although these data confirm the cardioprotective effects of HSD given immediately postburn, prehospital and early inhospital management of severely burned patients consists of aggressive crystalloid fluid resuscitation to correct intravascular volume deficits. The question arose as to whether delaying HSD for several hours after initiating crystalloid resuscitation would provide cardioprotection. MATERIALS AND METHODS: Third-degree scald burns comprising 45 +/- 1% of the total body surface area (burn groups, n = 40) or 0% for controls (group 1, n = 12) were produced; in groups 2 to 5, lactated Ringer's (LR) resuscitation was initiated immediately postburn according to the Parkland formula, 4 mL/kg/% burn. In group 2, (n = 12), LR was continued for 24 hours. HSD was administered as an i.v. bolus at either 1 hour (group 3, n = 10), 4 hours (group 4, n = 9), or 8 hours postburn (group 5, n = 9); immediately after HSD administration, LR was continued (1 mL/kg/% burn) until 24 hours postburn. RESULTS: Compared to sham burn controls, hearts from burned animals treated with LR alone had significant cardiac dysfunction, as indicated by a lower left ventricular pressure and +/- dP/dt. Compared with hearts from LR-treated animals, hearts from burned animals treated with HSD 1 hour (HSD-1) and 4 hours (HSD-4) after burn injury had significantly higher LVP and +/- dP/dt. Ventricular function curves calculated for HSD-1 and HSD-4 groups were comparable to those calculated for hearts from sham burns. Delaying HSD administration until 8 hours after burn provided little cardioprotection. CONCLUSIONS: Our data indicate that HSD effectively maintains cardiac function and reduces overall total fluid requirements if administered within 4 hours after burn injury.

Animals↗
PubMed1996

Direct current reduces wound edema after full-thickness burn injury in rats.

OBJECTIVE: To observe the effect of 4 and 40 microA direct current (DC) on edema formation after burn injury in rats. DESIGN, MATERIALS, AND METHODS: Silver-nylon wound dressings were used as either anodes (-) or cathodes (+) on 20% total body surface area full-thickness scalds in anesthetized male Sprague-Dawley rats. Untreated burned rats and rats treated with silver-nylon dressings without current were used as controls. MEASUREMENTS AND MAIN RESULTS: Immediately applied, continuous DC reduced burn edema by 17 to 48% at different times up to 48 hours postburn (p < 0.001). Neither reversal of electrode polarity nor change in current density had any significant effect on the results of treatment. Starting treatment during the first 8 hours postburn produced the least edema accumulation, but the reduction was significant even when DC was applied 36 hours afterburn. If started immediately after injury, treatment had to be continued a minimum of 8 hours to be most effective. CONCLUSIONS: Direct electric current has a beneficial effect in reducing wound edema after burn injury.

Animals↗
PubMed1996

Direct current reduces plasma protein extravasation after partial-thickness burn injury in rats.

OBJECTIVE: To observe the effect of 40 microA direct current (DC) on plasma albumin extravasation after burn injury. DESIGN, MATERIALS, AND METHODS: Silver-nylon wound dressings were used as anodes (-) on anesthetized male Sprague-Dawley rats with 20% total body surface partial-thickness scald burns. Burned rats with no treatment, or treated with silver-nylon dressing without current, were used as controls. Quantitative analysis of fluorescein isothiocyanate (FITC)-albumin leakage and accumulation in the wound tissue was performed using confocal fluorescence microscopy. MEASUREMENTS AND MAIN RESULTS: In controls, the rate of albumin leakage was maximal at 1 hour postburn (PB) and then decreased, but remained higher than normal for 48 hours PB. The accumulation of FITC-albumin was maximal 4 to 6 hours PB and substantial for 48 hours. When DC was applied, leakage was reduced by 30 to 45% and approached normal control rates by 8 hours PB. FITC-albumin concentration peaked 4 hours PB, was 18 to 48% less then in burned control, and approached the level observed in unburned control by 18 hours PB. CONCLUSIONS: DC has a beneficial effect in reducing plasma protein extravasation after burn injury.

Animals↗
PubMed1996

Combined insulin-like growth factor-1 and growth hormone improves weight loss and wound healing in burned rats.

UNLABELLED: The anabolic effects of growth hormone (GH) in burned patients appear to act both directly and through insulin-like growth factor-1 (IGF-1). We, therefore, hypothesize that exogenous GH plus IGF-1 will attenuate increases in metabolism and lean muscle wasting while promoting wound healing. MATERIALS AND METHODS: Rats, each weighing 440-470 g, were given a 35% total body surface area, full-thickness scald burn and divided into four groups to receive placebo (burned controls), bovine GH (2.5 mg/kg/day), IGF-1 (2.0 mg/kg/day), or bovine GH plus rhIGF-1 (2.5 + 2.0 mg/kg/day), respectively, for 8 weeks. RESULTS: Total body weight gain after 8 weeks averaged 110 g for GH plus IGF-1 compared with gains of 49 and 11 g for GH or IGF-1 alone, respectively. Burned controls lost 24 g. Metabolic rates were significantly reduced in all groups receiving growth hormones. Gastrocnemius muscle dry weight was significantly increased in those receiving GH plus IGF-1 compared with GH and IGF-1 alone or burned controls (p < .01). CONCLUSIONS: Data show that GH plus IGF-1 synergistically increased lean muscle weight, total body weight, and was more effective in re-epithelialization of the burn wound than either GH or IGF-1 alone.

Animals↗
PubMed1997

Down-regulation of tissue specific tumor necrosis factor-alpha in the liver and lung after burn injury and endotoxemia.

Burn injury and endotoxin lead to the development of a systemic inflammatory response. Because tumor necrosis factor-alpha (TNF-alpha) is a component of the proinflammatory response, we have determined the effect of burn injury and endotoxin in a murine model of thermal on tissue specific TNF-alpha levels in the liver and lung. Male mice were divided into four groups and injected with endotoxin (ETX) (2.5 mg/kg intraperitoneally) or saline (CNTL) or subjected to a 16% full-thickness scald burn (B), or ETX administration 72 hours after burn injury (B+ETX). Animals were killed at 0 to 24 hours after ETX or CNTL, 0 to 72 hours after B, and 72 to 96 hours after B+ETX (ETX administration 72 hours after B). TNF-alpha mRNA by Northern blot and protein analysis by enzyme-linked immunosorbent assay were determined and protein expressed as nanogram per gram of tissue. Statistical analysis was performed using analysis of variance with significance at p < 0.05. Burn injury did not result in detectable levels of liver or lung TNF protein or mRNA. Endotoxin administration resulted in a near six-fold rise in liver TNF protein compared with controls at 1, 2, and 6 hours after ETX (p < 0.05 to p < 0.001). Liver mRNA remained elevated from 20 minutes to 24 hours after ETX versus CNTL (p < 0.05). Endotoxin injection produced a persistent lung TNF protein elevation reaching significance at 1 and 2 hours (p < 0.001) and a rise in mRNA at 40 minutes to 6 hours (p < 0.05) versus CNTL. The liver showed a trend of reduced mRNA after B+ETX versus ETX (p = NS), whereas protein levels were reduced by 50 to 60% at 1 and 2 hours (p < 0.01). Lung mRNA values after B+ETX were only 40% compared with ETX at nearly all time points (p < 0.001) but were 15 times above CNTL values at 2 hours (p < 0.05). Based on these results, we conclude that burn injury did not cause an increase in liver or lung tissue specific TNF-alpha. However, the presence of a preexisting burn injury dramatically altered the response to endotoxin and the primary point of regulation appears to be at the posttranscriptional level.

Animals↗
PubMed1997

Induction of glutamine synthetase expression after major burn injury is tissue specific and temporally variable.

BACKGROUND: Major burn injury results in a translocation of amino acids from peripheral tissues to the abdominal viscera. Glutamine is a major participant in this event. Thermal injury causes a depletion of plasma and muscle glutamine pools as well as activation of proteolysis and release of glutamine from skeletal muscle. De novo synthesis of glutamine is regulated by the expression of the enzyme glutamine synthetase (GS). We studied the tissue-specific regulation of GS expression after thermal injury. METHODS: Burn injury of rats was produced by scalding of 25 or 40% of skin surface. In normal rats, four organs, including lung, muscle, kidney, and liver were assayed for relative GS messenger RNA content by Northern blotting 8 and 24 hours after 40% area burn. The effect of adrenalectomy on GS mRNA induction in muscle was assessed 24 hours after 25% area burn injury. RESULTS: GS mRNA levels were increased 2.3-fold in lung at 8 hours and 7.3-fold in muscle at 24 hours after burn injury. No appreciable increase in GS mRNA level was observed in kidney or liver. Muscle GS mRNA levels were lower than sham-operated controls in both burned and unburned adrenalectomized rats. However, adrenalectomy did not attenuate relative GS mRNA induction in muscle at 24 hours after burn injury. CONCLUSIONS: Burn injury causes an induction in GS mRNA levels in a tissue-specific fashion. Adrenalectomy greatly reduced GS mRNA levels, but did not completely block the induction of GS express in muscle after burn injury. This finding suggests that glucocorticoid hormones together with a unknown factor of nonadrenal origin influence this metabolic response to burn injury.

Adrenalectomy↗
PubMed1997

Influence of selective decontamination of the digestive tract on cell-mediated immune function and bacteria/endotoxin translocation in thermally injured rats.

OBJECTIVE: To determine the influence of pretreatment with selective decontamination of the digestive tract (SDD) on systemic immunosuppression, and the relationship between bacteria/endotoxin translocation and abnormalities of immune function in thermally injured rats. DESIGN, MATERIALS, AND METHODS: Animals were subjected to a 40% full-thickness scald injury, and divided into SDD-treated and control groups. The treatment group received SDD (polymyxin E, tobramycin, and 5-flucytosine) by gavage twice daily for 3 days before the experiment and continued for 5 days after thermal injury. The control group was given the same amount of water. The parameters reflecting cell-mediated immunity, including splenocyte proliferation in response to mitogens, interleukin 2 (IL-2) production, and lymphocyte subpopulation, were measured before injury and 1 and 5 days after burn, respectively. MEASUREMENTS AND MAIN RESULTS: Thermal injury resulted in marked reduction in splenocyte proliferative response to T-cell mitogens, IL-2 production, and T-helper/suppressor cells (CD4/CD8) ratio. Prophylactic treatment with SDD significantly decreased the incidences of bacterial translocation and endotoxemia, prevented suppressive mitogenic response and inadequate IL-2 production (p < 0.05-0.01) but did not affect the abnormal ratio of CD4 to CD8 T lymphocytes in blood (p > 0.05). CONCLUSIONS: These results suggest that bacteria/endotoxin translocation from the gut appears to be involved in cell-mediated immune dysfunction as a consequence of thermal injury. Pretreatment with SDD might attenuate postburn immunosuppression by preventing translocation events.

Animals↗
PubMed1997

Effects of burns on inhalation injury.

BACKGROUND: There are few studies of smoke injury combined with thermal burn. METHODS: Seven sheep (G1) received smoke injury alone; eight (G2) received a 40% full-thickness scald burn immediately after smoke injury. All animals were resuscitated with lactated Ringer's solution and killed 48 hours after injury. Cardiopulmonary variables and blood gases were measured serially. Ventilation perfusion distribution was analyzed using the multiple inert gas elimination technique. Lung wet to dry weight ratio and malondialdehyde levels were determined. RESULTS: G2 resulted in early significant hemodynamic changes. Serum total protein concentration was significantly lower and malondialdehyde significantly higher in G2. However, PaO2, lung wet to dry weight ratio, and ventilation perfusion mismatching in G2 did not differ from those in G1. CONCLUSIONS: Although the addition of burn injury exaggerated the lung lipid peroxidation and hypoproteinemia in the presence of more pronounced hemodynamic changes, the pulmonary dysfunction was not accentuated.

Animals↗
PubMed1998

Protein kinase C inhibition improves ventricular function after thermal trauma.

OBJECTIVE: To examine the effect of protein kinase C (PKC) inhibition on cardiac performance and intracellular Ca2+ homeostasis. DESIGN: Previous studies have shown that trauma impairs cardiac mechanical function, and recent studies suggest that PKC activation and subsequent perturbations in Ca2+ sequestration/release contribute to this cardiac dysfunction. In this study, anesthetized guinea pigs were given third-degree scald burns over 43 +/- 1% of the total body surface area and resuscitated with lactated Ringer's solution (LR) 4 mL/kg per percent of burn, Parkland formula. Animals with sham burns served as controls (n = 18). Burns were randomly divided into two groups: LR alone (N = 18) or LR + PKC inhibitor, calphostin C (0.1 mg/kg, intravenous bolus), given 30 minutes and 3, 6, and 21 hours after burn (n = 18). MATERIALS AND METHODS: Cardiac function was assessed by Langendorff preparation 24 hours after burn in 8 to 12 animals per group. Intracellular calcium concentration ([Ca2+]i) was measured in cardiac myocytes (collagenase digestion) from additional animals in each experimental group (n = 5-9 per group) after Fura-2 AM loading of myocytes; fluorescence ratios were measured with a Hitachi spectrofluorometer. RESULTS: Cardiac dysfunction occurred 24 hours after burn in LR burns as indicated by lower left ventricular pressure and a reduced rate of left ventricular pressure rise and fall, +/-dP/dt (61 +/- 3 mm Hg, 1,109 +/- 44 mm Hg/s, and 880 +/- 40 mm Hg/s, respectively) compared with values measured in sham-burned animals (86 +/- 2 mm Hg, 1365 +/- 43 mm Hg/s, and 1183 +/- 30 mm Hg/s, respectively; p < 0.05). Ventricular function curves confirmed significant postburn contractile depression despite aggressive fluid resuscitation. Cardiac injury in burned animals was indicated by an increase in perfusate creatine kinase and lactate dehydrogenase, and Ca2+ dyshomeostasis was confirmed by increased myocyte [Ca2+]i (sham 151 +/- 6 vs. burn 307 +/- 20 nmol/L, p < 0.05). PKC inhibition improved all indices of cardiac performance, producing left ventricular pressure (82 +/- 3 mm Hg), +/-dP/dt (1,441 +/- 48 and 1,294 +/- 32 mm Hg/s), and left ventricular function curves that were comparable with those of sham-burned animals. In addition, [Ca2+]i in calphostin-treated burned animals (154 +/- 11 nmol/L) was identical to values in sham-burned animals. CONCLUSION: Our data suggest that PKC may serve as a final common pathway in signal transduction events mediating postburn cardiac dysfunction.

Animals↗
PubMed1998

Epidemiology of childhood injury.

A review of childhood injuries at the Wesley Guild Hospital, a component of Obafemi Awolowo University Teaching Hospital Complex, Ile-Ife, Nigeria, showed that 1,471 patients seen in the children's emergency room during a period of 4 years (1992-1995) were there as a result of trauma, representing 9% of all patients seen. The case notes and accident and emergency cards of 1,224 were available for review. Ages ranged from 2 months to 15 years, with a mean of 6.9 years, and 40% of the patients were between 5 and 10 years of age. More males were affected than females, with a ratio of 1.5:1. Road traffic crashes were the most common causal factor, responsible for 324 injuries (26.5%). About 90% of these were pedestrians knocked down by automobiles and motorcycles. Passengers accounted for about 10% of the cases. Falls occurred in 305 patients (25%); 229 patients fell while on level ground either playing or running, accounting for 75%. There were 122 patients (10%) with misplaced foreign bodies; about 60% of these were recovered from the ears, and 26.3% from the nostrils. Edible seeds were the most common foreign bodies, followed by beads. Injuries from bites occurred in 108 patients, with dog and snake bites taking the lead. Burns, mainly from scalding, occurred in 89 patients. Other rare injuries were knife wounds, gunshot wounds, and injuries resulting from assaults. The home was the most common site of injury (570 patients, 46.7%) followed by streets or roadways (363 patients, 29.7%); 19.5% of injuries occurred at school. The most common anatomic region affected was the head and neck, followed by the limbs. One hundred ninety-seven patients (16%) had bony fractures, femurs being the most affected bone. Head injury was seen in 104 patients, representing 8.5%, although only 17 of these injuries were severe. There were 10 cases of abdominal injury and 9 cases of chest injury, representing 0.8 and 0.7%, respectively. Wound infection occurred in 6.4% of the patients. Death occurred in 19 patients, accounting for 1.6%; 10 of these patients had severe head injuries. Road traffic injuries and burns accounted for the greatest number of complications. The findings of this study suggest that trauma is an important factor in childhood morbidity and mortality in our environment, with road traffic injuries taking the lead. Preschool pedestrian children were most commonly affected, the majority of them on errands for their parents. We believe that the majority of these injuries are preventable.

Adolescent↗
PubMed1998

Prostaglandin E2 alterations during sepsis are partially mediated by endotoxin-induced inhibition of prostaglandin 15-hydroxydehydrogenase.

Prostaglandin E2 (PGE2) is significantly elevated in the plasma of septic or injured patients and is thought to be a component of the resultant immune suppression associated with augmented rates of infection and mortality. Many studies have examined the effect of burn injury and sepsis on PGE2 synthesis. However, the effect of sepsis or burn injury on the expression of prostaglandin 15-hydroxydehydrogenase (PGDH), the key enzyme responsible for PGE2 degradation, has not been explored. The aim of this study was to examine the effect of endotoxin treatment and/or burn injury on the expression of PGDH. Male BDF1 mice were assigned to four groups (n = 4/group): sham, lipopolysaccharide (LPS) (2.5 mg/kg, Escherichia coli LPS, i.p.), burn (15% body surface area scald injury), and burn + LPS (15% body surface area + 2.5 mg/kg LPS, i.p.). Lung tissue was harvested at specific time points after treatment and subsequently was processed for total RNA and protein. Northern and Western blot analyses were used to examine differences in PGDH protein and mRNA expression. Total RNA was probed with the riboprobe for murine PGDH, and the 100,000 g protein fraction was immunoblotted using an rabbit antimurine PGDH antibody. PGDH was expressed in lung at t = 0 in both the saline and LPS-treated animals. A decrease in mRNA expression was initially observed at 2 hours after LPS treatment. The decrease was also significant (p < 0.05) at 3 hours after LPS and maximal decrease in mRNA and protein expression was observed at 6 hours. At 24 hours after LPS administration, the PGDH mRNA and protein expression was still significantly depressed to 49% of control expression. PGDH expression was similar and not statistically different in both burn and burn + LPS treatment at t = 0. At 2 hours after LPS, PGDH mRNA expression in the burn + LPS treatment group had significantly decreased to 47% in comparison with the burn alone group. Maximal decrease in PGDH mRNA and protein expression in lung from burn + LPS was observed at 6 hours after LPS treatment. This change represents a 73% decrease in mRNA in comparison with the time-matched burn control. At 24 hours after LPS administration, PGDH mRNA but not protein expression in the lung from burn + LPS treated mice was still significantly decreased. In summary, LPS treatment alters PGDH mRNA expression at the transcriptional and protein levels. Consequently, sepsis-induced increases in PGE2 levels may not be only due to increased PGE2 synthesis but also due to decreased PGDH expression and, hence, PGE2 degradation.

Animals↗
PubMed1998

Cyclooxygenase-2 inhibitor NS-398 improves survival and restores leukocyte counts in burn infection.

BACKGROUND: Cyclooxygenase-2 (COX-2) is a key enzyme in the production of prostaglandin E2 (PGE2) from activated macrophages. PGE2 is increased during trauma and sepsis and has been implicated as a negative immunomodulator. The objective of this study was to determine the therapeutic benefits of a COX-2 inhibitor (NS-398) on survival and leukocyte production in a murine model of burn sepsis. METHODS: To determine the in vitro ability of NS-398 to inhibit macrophage production of PGE2, peritoneal elicited macrophages were stimulated for 18 hours with medium alone, endotoxin (ETX) (1 mumol/L), or ETX plus NS-398 (0.3 mumol/L). Macrophage supernatant PGE2 levels were determined by an enzyme immunoassay. To test the in vivo efficacy of NS-398, mice subjected to a 15% dorsal scald burn plus 1,000 colony-forming units of topical Pseudomonas aeruginosa received either 10 mg/kg NS-398 intraperitoneally or placebo 4 to 6 hours after infection and twice daily for 3 days. Survival was measured up to 14 days, and circulating white blood cell (WBC) count and absolute neutrophil count (ANC) were determined 3 days after injury. RESULTS: Macrophage PGE2 production was significantly increased in the ETX-treated group compared with the medium-alone group, and this increase was completely normalized with the addition of NS-398. NS-398 also augmented WBC count (4,288 +/- 649 vs. 7,866 +/- 435 per mm3; p < 0.01) and ANC (1,068 +/- 255 vs. 3,663 +/- 474 per mm3) after burn infection and attenuated macrophage depression of hematopoietic proliferation. Finally, NS-398 treatment significantly improved survival after burn infection, from 0 to 45.5%. CONCLUSION: Inhibition of the COX-2 isoform of cyclooxygenase with NS-398 inhibited macrophage PGE2 production, restored ANC, and improved survival during burn infection. NS-398, therefore, has potential therapeutic benefits in septic patients who have developed neutropenia.

Animals↗
PubMed1999

The effects of diaspirin cross-linked hemoglobin on hemodynamics, metabolic acidosis, and survival in burned rats.

OBJECTIVE: Diaspirin cross-linked hemoglobin (DCLHb) is a vasoactive hemoglobin-based oxygen carrier or "blood substitute" that has been shown to improve base deficit in several experimental studies of hemorrhagic shock. Our objective was to determine if the addition of DCLHb to the resuscitation regimen would improve hemodynamic parameters, metabolic acidosis, and survival in our rat burn shock model compared with currently used resuscitation therapy. METHODS: This was a randomized, controlled, experimental rat study. Male Wistar rats, weighing 200 to 250 g, were surgically prepared for an acute study. After placement of indwelling catheters, baseline hemodynamic values (mean arterial pressure, cardiac output, systemic vascular resistance, stroke volume, and base excess) were obtained. Thirty-two rats were used in the study, and they were either subjected to a 30% scald burn (experimental group) or sham burned (control group). The experimental animals were immediately intravenously resuscitated and followed for 6 hours. The resuscitation was based on the Parkland formula (4 mL/kg for each 1% of total body surface area [TBSA] burn), with 50% of the calculated fluid amount to be administered at a constant rate during the first 8 hours after burn. The animals were resuscitated for 6 hours and received between 9.00 and 11.25 mL of fluid depending on weight. The experimental animals were randomly assigned to one of three treatment groups: group I, lactated Ringer's solution; group II, lactated Ringer's solution-human serum albumin; group III, lactated Ringer's solution-DCLHb. Group I (n = 8) received 4 mL/kg lactated Ringer's solution for each 1% of TBSA burn. Group II (n = 8) received 2 mL/kg lactated Ringer's solution and 2 mL/kg human serum albumin for each 1% of TBSA burn. Group III (n = 8) received 2 mL/kg lactated Ringer's solution and 2 mL/kg DCLHb for each 1% of TBSA burn. The sham group (n = 8) was not burned and was not resuscitated. Animals that survived up to 6 six hours were killed. RESULTS: We found that mean arterial pressure, cardiac output, stroke volume, and base excess were all improved in the DCLHb-lactated Ringer's solution-treated animals compared with the other experimental treatment groups. The 6-hour mortality rates were zero of eight (lactated Ringer's solution-DCLHb group), zero of eight (sham group), three of eight (lactated Ringer's solution-human serum albumin group), and six of eight (lactated Ringer's solution only group). CONCLUSION: Early resuscitation with DCLHb is superior to non-oxygen-carrying resuscitative fluids in improving hemodynamics and survival in this model of burn shock. DCLHb might improve general tissue perfusion in the acute postburn period, and it could be useful in the early management of patients with severe burns.

Acidosis↗
PubMed1999

Direct current reduces accumulation of Evans Blue albumin in full-thickness burns.

BACKGROUND: Application of direct current (DC) to a burn wound limits extension of the zone-of-stasis and reduces wound tissue edema. OBJECTIVE: To study the effects of DC on extravasation of plasma proteins after burn by using Evans blue (EB) as a marker of plasma albumin. MATERIALS AND METHODS: Male Sprague-Dawley rats with 20% total body surface area full-thickness scalds (100 degrees C/10 sec) were used as the experimental model. Burn wounds were treated with plain nylon, silver-nylon, silver-nylon and 40 microA DC, or no dressing. EB (30 mg/kg) was injected immediately or at variably delayed postburn (PB) times and accompanied by DC application at various time intervals PB. Tissue content of Evans blue was assessed at different times after injection of the dye or infliction of burn injury. RESULTS: Evans blue albumin (EBA) concentration in untreated burn wounds (307.7 microg/g tissue) was nine times greater than in unburned skin (36.5 microg/g tissue) at 48 hours PB. When animals received a DC and EB injection immediately PB, DC treatment reduced EBA concentration by 60% at any time point PB. When EB was injected immediately PB, or at variably delayed times PB, accompanied by DC immediately PB, or at variably delayed times PB, DC reduced EBA accumulation at all examined times PB by more the 50% (p < 0.001). CONCLUSION: EBA and edema fluid accumulation in burn wound change in concert after injury and show similar response to DC treatment.

Animals↗