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Ultrastructural aspects of cooled thermal injury.

This study reports on the effects of early cooling on the morphology of partial-thickness burns. After 10% body surface dorsal scald burns at 75 degrees C for 10 seconds, guinea pigs were treated by ice-water immersion at 10 minutes postburn of only the burned surface for 30 minutes. Skin samples from treated and untreated burn wounds were examined at 2, 8, 24, and 96 hours postburn by light and electron microscopy. During the first 24 hours, cooling was associated with reduced loss of epidermis and reduced damage to the basement membrane. There was also less damage to the dermal microvasculature and less edema fluid compared to untreated burn wounds. At 96 hours, the cooled burn wounds demonstrated minimal dermal hemorrhage and polymorphonuclear leukocytic infiltration, compared to the untreated wounds. These results indicate that on a cellular level, cooling has beneficial effects on the experimental burn wound.

Analgesia↗

Effect of thermal injury on glucocorticoid and androgen binding in skeletal muscles with different fiber populations.

The role of glucocorticoids and androgens in postburn augmentation of skeletal muscle proteolysis was investigated following a 3-second single hindlimb scald (6 to 7% body surface area) in the rat. Soleus muscles and calf muscles from the burned and unburned hindlimbs were excised 3 days postburn and compared to age-matched controls to evaluate both the local and systemic effects of burn injury. Free tyrosine content in soleus and calf muscles of the burned limb was 30% and 58%, respectively, higher than in corresponding control muscles. Net proteolysis in burned limb soleus muscles, as measured by tyrosine "production' in vitro, was more than doubled as compared to controls. In contrast, tyrosine content and production by muscles from the unburned limb of burned rats dis not differ from controls. Specific binding of the glucocorticoid dexamethasone in cytosols of burned limb soleus and calf muscles was more than 80% below control level. Soleus muscles from the unburned limb of burned rats showed a 60% decrease in dexamethasone binding but that of the unburned limb calf muscles did not differ from controls. The latter difference and the observation in control rats of a relatively lower dexamethasone binding in calf muscles as compared to soleus muscles suggest that the glucocorticoid binding could be influenced by the type of fibers comprising the muscle. Unlike the glucocorticoid binding, neither the thermal injury nor the muscle fiber type had a significant effect on specific cytosolic binding of the androgen methyltrienolone by the muscle tissues studies. It is concluded that thermal injury restricted to one hindlimb leads to regional differences in skeletal muscle proteolysis and glucocorticoid binding. Muscles of the burned region exhibit stimulation of proteolysis and virtual disappearance of cytosolic glucocorticoid receptors. Muscles from the unburned region appear to have a normal rate of proteolysis and either normal or decreased glucocorticoid binding. It remains to be elucidated whether the decrease in cytosolic glucocorticoid receptors is due to changes in receptor synthesis and degradation, or to accelerated translocation of the receptors into the nucleus.

Androgens↗

The effect of ketanserin, a specific serotonin antagonist, on burn shock hemodynamic parameters in a porcine burn model.

A number of vasoactive substances, including serotonin, have been implicated in the pathophysiology of burn shock. Ketanserin, a specific serotonin antagonist, was investigated in a porcine burn shock model. Fifteen swine were given a mean 44% total body surface area full-thickness scald burn and received fluid resuscitation with Ringer's lactate for 24 hours postburn. The swine were divided into three groups: Group I (control group) received no ketanserin; Group II received ketanserin as a single intramuscular dose preburn and continuously via intravenous drip postburn; and Group III received ketanserin continuously via intravenous drip postburn only. The ketanserin-treated groups demonstrated improved cardiac index, decreased pulmonary artery pressures, and smaller arteriovenous oxygen content differences compared to the control group in the early postburn period. Ketanserin should be investigated further as a possible adjunctive therapeutic agent during burn shock resuscitation.

Animals↗

Hepatocyte dysfunction in thermal injury.

Transmembrane potential difference (PD) is a reliable indicator of cellular function. Decreased PD in hepatocytes in hemorrhagic shock occurred concomitant with decreased adenosine triphosphate (ATP), suggesting energy depletion as the mechanism of cell dysfunction. This study correlates changes in liver and muscle PD with hepatocyte ATP, glucose-6-phosphate (G-6-P), and lactate levels in burn shock and resuscitation. Six adult female baboons were subjected to 52.4 +/- 6.3% body surface area third-degree scald burns. The animals were resuscitated using the Parkland formula, after the muscle PD had fallen to -70 mV. Liver PD decreased from 46.2 +/- 2.4 mV to 22.4 +/- 3.8 mV in burn shock. The PD recovered toward normal with resuscitation. ATP and G-6-P contents did not change significantly, while lactate rose threefold in burn shock. A severe cellular derangement was indicated by this marked hepatocyte depolarization. Maintenance of normal intracellular ATP excludes energy depletion as the mechanism of this cell dysfunction. These findings are consistent with failure of active ion transport or changes in cell membrane permeability which were partially recovered during fluid resuscitation.

Adenosine Triphosphate↗

Relative roles of burn injury, wound colonization, and wound infection in induction of alterations of complement function in a guinea pig model of burn injury.

Stimuli involved in induction of alterations of the complement system and production of circulating inhibitor(s) of phagocytic function of polymorphonuclear neutrophils following burn injury were investigated using a guinea pig model of scald burn injury. The activity of C1-C9, assessed by measurement of total hemolytic complement, was found to increase primarily in response to burn injury per se, whereas reduction in the activity of the alternative complement pathway was shown to develop in association with natural colonization and local burn wound infection with bacterial pathogens. Invasive burn wound infection induced experimentally with Staphylococcus aureus, Pseudomonas aeruginosa, or Candida albicans exacerbated this latter abnormality, caused consumption of C1-C9 activity, and was associated with appearance of serum factors that depressed phagocytosis of Escherichia coli 075 by peritoneal polymorphonuclear neutrophils. Thus injury and coexistent infection both play important roles in induction of humoral alterations of host defense associated with burn injury.

Animals↗

Cimetidine therapy for burn shock: a quantitative assessment.

Optimal cardiac output (CO) resuscitation for severely burned guinea pigs is obtained with intravenous volumes of lactated Ringer's (LR) calculated at 4 cc/kg/%burn/24 hr. When one half this volume of LR is given (2 cc/kg/%burn/24 hr) CO is significantly (p less than 0.05) reduced at 2, 4, and 8 hours after injury. When early postburn cimetidine therapy (0.5 hours after injury) is added to only 1 cc/kg/%burn/24 hr LR, CO is significantly elevated for the same time periods and is not significantly different from CO values of LR at 4 cc/kg/%burn/24 hr for the first 24 hours after injury. However, postburn cimetidine therapy delayed until 1 hour after burn injury did not improve CO compared to treatment with LR at 2 cc/kg/%burn/24 hr. These observations suggest that early postburn cimetidine therapy administered within 1/2-hour of severe scald injury will result in significant CO improvement while simultaneously reducing resuscitative fluid volume requirements by as much as 70% for the first 24 hours after injury.

Animals↗

Reduced serum T4 and T3 and their altered serum binding after burn injury in rats.

Total T4 and T3 concentrations are often suppressed in burned patients. To investigate the significance of such changes, we have characterized serum T4 and T3 after full-thickness scald burns (60% body surface under anesthesia) of 270-gm male Sprague-Dawley rats housed in a light:dark cycle of 14:10 hr. Groups (N = 9-15) of BURN, SHAM (anesthesia, fur clipped, no burn) and CON (controls) were sacrificed on postburn days 8 and 14. T4 and T3 (radioimmunoassay), free indices (FT4I and FT3I = respective total T4 or T3 X in vitro charcoal T3 uptake, T3U), and free concentrations (FT4 and FT3 = total T4 or T3 X respective equilibrium dialyzable fraction, T4DF or T3DF) were not different between CON and SHAM. Compared to SHAM, mean T4 and FT4I (by about 48% of respective SHAM means on both days), TT3 (by 36, 43%), and FT3I (by 38, 45%) (days 8, 14) were suppressed in BURN (all p less than 0.001). T4DF (both days) and T3DF (day 14) were significantly elevated in BURN, demonstrating a deficit in serum binding, but T3U was not. FT4 (by 26, 22%) and FT3 (by 33, 34%) (day 8, 14) were significantly lower in BURN. On either day, covariance analyses (BURN vs. combined CON + SHAM) correlated FT4I or FT3I with respective FT4 or FT3 (all p less than 0.001, slopes not different in BURN vs. CON + SHAM), but the lower FT4I and FT3I in BURN significantly overestimated (all p less than 0.001) the depression of respective FT4 and FT3 in BURN.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Acute respiratory distress syndrome (ARDS): the prophylactic effect of neurodepressant agents.

It has been suggested that acute respiratory distress syndrome (ARDS) is induced by a cybernetic imbalance of the central nervous system secondary to alarm reaction-provoked intravascular coagulation into cerebral microvessels. The brain metabolic and electrical resting state through the use of neurodepressant drugs might theoretically reduce the intensity and duration of the alarm reaction, thus diminishing the possibility of self-induced secondary brain lesions. In this work, Wistar rats were submitted to central (anterior hypothalamic electrolytic lesion) and peripheral (scald burn) trauma as effective models of reproducing an ARDS-like syndrome. Pretreatment of these animals with the following neurodepressant drugs: morphine, pentobarbital sodium, haloperidol, diazepam, chlorpromazine, and urethane, resulted in significant attenuation of the evolution of the ARDS-like syndrome, reinforcing the suggestion of a centrally-based origin of such pathologic manifestations.

Animals↗

The effects of burn injury and fluid resuscitation on cardiac function in vitro.

The effects of a 30% full-thickness total body surface area scald burn on in vitro mechanical cardiac function was studied in Sprague-Dawley rats. The findings were a 50% decrease in tension development and velocities of contraction and relaxation, when papillary muscle functions from sham and unresuscitated burned animals were compared. Fluid resuscitation synchronous with burning completely reversed the defects in papillary muscle function. This defect in function was partially transferable to normal muscles incubated in serum from burned rats.

Animals↗

Epidemiology of work-related burn injuries in Massachusetts requiring hospitalization.

To describe the epidemiology of hospitalized, work-related burns among Massachusetts residents aged 16 years or older, 825 Massachusetts residents who were burned between 1 July 1978 and 30 June 1979, and who were treated as hospital inpatients in any of 240 New England hospitals, were studied. Two hundred forty (29%) of the 825 identified burns were known to be work-related. Our findings suggest that the workplace is a major contributor to hospitalized burn injury among employed males, accounting for 60% of their burns. Young workers and black workers experienced the highest rates of burning, with rates two and four times higher than their older and white counterparts, respectively. Scalds were the most common type of work-related burn injury for individuals in each age category, accounting for 45% of the burns overall.

Accidents, Occupational↗

Effect of exchange transfusion on cell-mediated immune function following thermal injury.

We assessed the effect of syngeneic and allogeneic exchange transfusion (XTF) on cell-mediated immunity in a murine burn model. Mice were given a 30% TBSA scald injury and lymphocyte function was monitored with the popliteal lymph node assay for host-versus-graft (HVG) or graft-versus-host (GVH) response. Nonexchanged burned animals exhibited suppression of GVH response on postburn days (PBD) 3 and 8 and suppression of HVG response on PBD 3, 8, 11, and 14. Syngeneic XTF stimulated GVH response on PBD 3, and significantly improved both GVH and HVG response to alloantigens on postburn days 3 and 8 compared to the response of burned controls. Allogeneic XTF significantly improved GVH response on PBD 3 and 8, but did not improve HVG response. Restoration of lymphocyte function in all experimental groups occurred between PBD 14 and 18 and coincided with wound healing.

Animals↗

Altered leukocyte delivery to specific and nonspecific inflammatory skin lesions following burn injury.

This study assessed the effect of burn trauma on the in vivo leukocyte cell delivery during the first 24 hr of the delayed type hypersensitivity (DTH) skin test reaction and a bacterial skin abscess. Inbred male Lewis rats sensitized to keyhole limpet hemocyanin (KLH) were given a 30% scald burn or sham burn. Three days later the animals were injected intradermally, at different sites, with 0.3 mg of KLH, 10(8) organisms of S. aureus 502A, and 0.1 cc of saline, at 2 to 24 hr. Leukocytes labelled with Indium111 oxine(leu111) were injected intravenously. In sham rats the peak leu111 influx in the DTH reaction occurred at 2-4 hr while in the abscess it was biphasic with peaks at 3 hr and 6-8 hr. In burn trauma rats there was a markedly increased leu111 peak at 2 hr in both the DTH and abscess reactions followed by a significantly lower than normal leu111 delivery in the late (6-24) hours. This marked early leukocyte influx in burned rats was paralleled by a reduced DTH skin test lesion (8.2 +/- 1.1 mm to 4.2 +/- 1.1 mm) and an increased bacterial abscess (5.1 +/- 1.1 mm to 8.1 +/- 0.9 mm) post burn. There was a direct correlation between leukocyte cell delivery to a DTH reaction and a bacterial abscess (r8 = 0.69, Spearman rank; p less than 0.001). We conclude that burn trauma results in altered leukocyte delivery to inflammatory lesions and the DTH response can be used to assess the ability of a burn trauma host to recruit leukocytes at a site of infection.

Abscess↗

Flow cytometric characterization of rat thymus cells in a radiation-dominated model of combined injury.

Thymuses of rats that had been: a) gamma-irradiated [500 cGy whole-body radiation (R)], or b) thermally injured [20% BSA dorsal, scald burn (TI)], or c) combined injured [irradiation followed by burn (CI)] were studied for involution and recovery processes after sublethal treatments. The expression of surface antigens on thymic cells before and after injuries was evaluated using the monoclonal antibodies (mcAB) MRC OX4, MRC OX7, MRC OX8, W3/13 HLK, and W3/25 and flow cytometric analysis. Thymic cellularity decreased to less than 1% of normal (N), age-matched rats by 4 days after R or CI. Recovery reached 60% to 70% of N by 28 days post treatments. TI caused a biphasic thymic recovery pattern with nadirs of 40% of N on days 7 and 21. Recovery at day 28 was similar to that after R and CI. Expression of OX7, OX8, W3/13, and W3/25 antigens all reached nadirs of 40% of N by day 4 after R and CI. Recovery of antigen expression, except for W3/25, was near completion by day 7 after R and CI. Changes in antigen expression after TI were less pronounced for all mcAB tested. Decreases in labeling of thymocytes with the helper T-cell marker, W3/25, observed after TI, could not be correlated with elevated expressions of the suppressor/cytotoxic T-lymphocyte antigen, OX8. Variations in relative labeling of nonlymphoid thymic cells with OX4 (Ia-antigen) reflected the disappearance and recovery of radiosensitive lymphoid thymocytes. The similarity of results after R and CI demonstrate that the model of CI is 'radiation-dominated.' The addition of burn injury to radiation trauma had no synergistically damaging effect on the parameters studied.

Animals↗

Therapeutic effects of silver nylon dressings with weak direct current on Pseudomonas aeruginosa-infected burn wounds.

The therapeutic and prophylactic effects of nylon dressings coated with metallic silver in a direct current circuit have been examined in a rat model of fatal burn wound sepsis. Male Sprague-Dawley rats weighing 325 +/- 25 grams with 20% full-thickness scald injuries were used. Therapeutic effects were examined at 4 or 24 hours after surface inoculation with a lethal dose of Pseudomonas aeruginosa (Strain 59-1244). When used as a surface anode with an implanted silver needle cathode, the silver nylon was therapeutic at currents between 0.4 and 40 microA when applied at either test time and continued for 5 days (p less than 0.001). When used as a cathode, silver nylon was not effective. Nylon cloth without a silver metal coating was not effective without applied current or when used as an anode. Silver nylon dressings placed at 4 hours after inoculation but without applied current showed significant effectiveness (p less than 0.01). This effect, however, was significantly less than that seen with silver nylon used as an anode (p less than 0.001). Barrier prophylactic effects were examined by placing silver nylon or uncoated nylon on burn wounds before inoculation with Pseudomonas aeruginosa. The uncoated nylon had no barrier effect. Silver nylon was found protective but applied current was not required for significant (p less than 0.001) barrier effect. These results indicate silver nylon dressings may be a valuable antimicrobial burn wound covering device.

Animals↗

Complement-mediated hemodynamic depression in the early postburn period.

This study examines the influence of complement on systemic hemodynamics following severe thermal injury in rats. Animals were injected intraperitoneally at t = -36 and t = -24 hours with either cobra venom factor (20 units/kg/dose; n = 56) to delete circulating complement or with saline alone (n = 64). Rats within each subset were then subjected to either a 50% TBSA full-thickness scald burn or sham burn. Cardiac output (CO), mean arterial pressure (MAP), heart rate, systemic vascular resistance (SVR), stroke volume, and cardiac power as well as hematocrit and the change in per cent complement activity were determined at various time periods between 15 minutes and 25 hours after the burn. In normocomplementemic animals the burn produced a marked early (t = 3-6 hours) depression in CO and MAP with a rise in SVR. Over time the hemodynamics returned to normal (t = 12 hours) and eventually approached a hyperdynamic response (t = 24 hours). Serum hemolytic complement activity fell immediately and progressively after the burn, indicating significant complement activation. Complement depletion attenuated the early decline in CO and sharply lowered the rise in SVR in the early postburn period. In addition, complement depletion improved heart rate and stroke volume and appeared to preserve/enhance late (t = 24 hours) cardiac function. This study suggests that complement activation contributes to the depression in cardiac output in the early postburn period.

Animals↗

Effectiveness of hypertonic saline-dextran 70 for initial fluid resuscitation of major burns.

Small-volume resuscitation (4 ml/kg) with hypertonic saline-dextran (HSD) has been shown effective in hemorrhagic shock. In the present study the effectiveness of an initial 4 ml/kg bolus infusion of HSD on cardiovascular function and fluid resuscitation requirements after a major burn injury was evaluated in anesthetized sheep following a 40% BSA scald burn. One hour after injury resuscitation was initiated by a rapid intravenous bolus infusion (4 ml/kg) of either hypertonic saline-dextran (7.5% NaCl in 6% dextran 70) (HSD) or the same volume of normal (isotonic) saline (NS). Lactated Ringer's was later infused as needed to maintain cardiac output at 90% of baseline. HSD rapidly and effectively restored cardiac output and mean arterial pressure significantly better than the same volume of NS. Hemodynamic improvement by HSD was short lived, and need for further fluid therapy was only marginally delayed (HSD 38 +/- 8 min, NS 20 +/- 3 min; p = 0.06) (mean +/- SEM). The total requirements for fluid therapy during the first 6 hr postburn were not reduced by the initial HSD bolus (HSD 3,145 +/- 605 ml, NS 2,905 +/- 495 ml; n.s.), nor was skin edema formation reduced. We conclude that in anesthetized sheep HSD resuscitation was only transiently effective in treating burn shock. This may be attributed to the sustained increase in vascular permeability and continued plasma leak following thermal injury.

Animals↗

Antibiotic prophylaxis diminishes bacterial translocation but not mortality in experimental burn wound sepsis.

Pseudomonas (PSA) burn wound sepsis results in prolonged bacterial translocation (BT) of enteric organisms such as E. coli to the mesenteric lymph nodes (MLN) and organs in rats. Intestinal decontamination with oral antibiotics may improve mortality after burn injury, perhaps due to decreased BT. To determine the effect of oral antibiotic prophylaxis effective against E. coli but not PSA on BT and subsequent mortality in a model of PSA burn wound sepsis, rats were given a 30% scald burn and wound inoculation with 10(8) PSA followed by randomization to either ampicillin (50 mg/kg/d) or saline gavage. Cultures of MLN, organs, blood, and cecal contents were obtained on days 1, 4, and 7 after injury, with additional animals observed for 14-day mortality. Although oral antibiotic prophylaxis resulted in increased cecal colony counts, the incidence of BT was unchanged. The number of organisms present in both the MLN and organs, however, was significantly reduced with prophylaxis, indicating cecal overgrowth by non-translocating bacteria. Reduction of the number of translocating organisms did not result in improved mean survival time after injury, suggesting that mortality from PSA burn wound sepsis occurs independently of bacterial translocation.

Ampicillin↗

Hypertonic saline dextran resuscitation fails to improve cardiac function in neonatal and senescent burned guinea pigs.

Our previous studies suggested that the greater diminution in burn-induced cardiac contractile function which occurs in young and elderly subjects compared with adult subjects is related to differences in intracellular calcium availability to the myofilaments. We recently showed that improved cardiac function after hypertonic saline dextran (HSD) resuscitation from burn injury in adults was related to enhanced intracellular calcium content. In the study presented here, 126 hearts isolated from neonatal, adult, and senescent guinea pigs were used to evaluate age-related differences in cardiac contractile response to HSD resuscitation from burn injury. Scald burn was induced in 30 adult, 18 neonatal, and 30 senescent guinea pigs; within each age group, half of the burned animals were resuscitated with lactated Ringer's (Parkland formula, 4 mL/kg/% burn for 24 hours); half received an initial bolus of HSD (4 mL/kg, IV) plus lactated Ringer's (1 mL/kg/% burn for 24 hours). An additional 16 animals from each age group served as sham burn controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗