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The effects of omega-3 fatty acid rich oil (MaxEPA oil), omega-6 fatty acid rich oil (soybean oil), and a combination of omega-3 and omega-6 oils (MaxEPA oil + soybean oil) on cardiovascular health-related parameters of thermally injured and control (sham) rabbits were determined. Plasma and platelet analyses of burned rabbits fed with MaxEPA oil revealed significantly higher concentrations of eicosapentaenoic acid and docosahexaenoic acid + myristic acid. Linolenic acid concentrations declined in animals supplemented with soybean oil + MaxEPA oil. At the end of this study the lowest concentrations of linoleic acid and arachidonic acid were found in the sham and burned groups supplemented with soybean oil + MaxEPA oil. Overall, favorable significant differences in plasma and platelet fatty acids concentrations were found in burned or sham groups supplemented with MaxEPA when compared with those of groups supplemented with soybean oil. These favorable changes in plasma and platelet lipids may have an impact on the risk of cardiovascular disease in thermally injured patients.

In this article we develop a calculation or formula for use in determining the potential dilution effect of fluids administered during patient treatment on serologic testing parameters. The formula uses basic principles of (a) fluid distribution over time from administration; (b) ratios of plasma and extravascular fluid volumes to body weight; and (c) common practices of fluid resuscitation. A dilution threshold of 50% was set using data from enzyme-linked immunosorbent assay human immunodeficiency virus antibody determinations performed on in vitro diluted seropositive serum samples. These data respond to issues raised by guidelines from the Centers for Disease Control and the U.S. Food and Drug Administration to achieve recipient safety without unnecessarily restricting the potential donor pool.

Two catalytically active proteases, dipeptidyl peptidase IV (DP IV) and aminopeptidase (AP), not previously reported as present in burn wound exudates, have been identified by substrate specificity and susceptibility to known enzyme inhibitors. The ratio of the two enzymes in exudates is significantly different from the ratio in plasma collected from the same patient during the same time interval, suggesting that measurement of exudate components may be more significant than plasma activities in evaluating local conditions in the wound. A number of biologically significant substances are DP IV substrates, and the list can be considerably extended by the sequential action of AP and DP IV. Some polypeptides are converted to their biologically active form by DP IV action, while others are degraded to inactive forms. Either action generates X-Pro dipeptides, which have a demonstrably beneficial effect on wound healing. Although not resolved by molecular sizing or anion exchange chromatography, DP IV and AP in a burn wound exudate were purified by affinity chromatography.

Proteolytic (caseinolytic) activity in burn wound exudates was screened over the range pH 5.3 to 8.4. Although activity was greatest at pH 8.4 in four of seven exudates, individual differences indicated that different proteases predominate in the local environment of the wound. Paired exudate and serum samples were compared with regard to fibrin degradation products and three protease inhibitors: antithrombin III, a1-protease inhibitor, and a2-antiplasmin. Fibrin degradation products concentration was higher in exudates than in paired sera, indicating the wound as the source of circulating fibrin degradation products rather than intravascular coagulation followed by fibrinolysis. In contrast, all three protease inhibitors exhibited higher concentrations in serum than in the paired exudate. The serum/exudate ratio for AT III differed significantly from that for a1-protease inhibitor and a2-antiplasmin, and the ratio of two inhibitors in serum differed from the ratio of the same two inhibitors in the exudate in two of three comparisons. These findings emphasize the importance of exudate examinations as a reflection of events in the wound itself. The importance of microenvironments is invoked to account for the significant exudate fibrin degradation products titers, which are seen despite the presence of antithrombin III, which could inhibit coagulation, and the presence of a2-antiplasmin, which could inhibit fibrin degradation.

A dorsal skin flap chamber model was developed for analysis of the microvascular response to moderate intensity local thermal burns. Fluorescein isothiocyanate tagged 70,000 d dextran was introduced to visualize the extravasation and interstitial transport of macromolecules at the burn site. Contact burns 0.5 cm in diameter were affected by touching a thermostated metal rod onto the exposed epidermal side of the chamber preparation. All burns were of 5-second duration at temperatures between 55 degrees C and 70 degrees C. Postburn leakage of the fluorescein-labeled probed was monitored at numerous sites in the preparation on a fluorescent microscope equipped with a low-light-level intensified silicon intensified target video camera and recorded on tape for subsequent quantitative analysis. Selected scenes were digitized and subjected to a sequence of computer-image processing operations to extract quantitative information about the concentration distribution and net accumulation of dextran in the interstitial space as a function of postburn time. A diffusion model based on cylindrical geometry was fit to the concentration profile data at each site analyzed, and an apparent diffusion coefficient describing the interstitial transport process was determined. The interstitial transport increased with burn temperature up to a threshold of 70 degrees C, where other factors resulted in significant reduction in the loss of fluorescent macromolecule from the vasculature.

Alterations in the cutaneous vasomotion function caused by scald burns to a large area on the flank were observed and quantified in a dorsal skin flap window with a hamster model. Subsequent to chronic implantation of the window chamber to provide direct microscopic observation of blood flow for an entire thickness of skin, control measurements of vasoactivity in a defined network of arterioles were taken by means of a digital video image splitter over a period of several days. A 100 degrees C, 5-second water scald was then effected over 17% to 55% of the total body surface area, and the vasoactivity was remeasured in the targeted set of sites at serial time intervals for 2 to 4 days. Data were acquired directly into a computer and analyzed for both the magnitude and time pattern of diameter fluctuations during 3-minute observation periods. Average and standard deviations of diameters were computed, and the Prony power spectral analysis method was applied to identify the presence and strength of fluctuation frequencies. In general, vasomotion was suppressed for several hours subsequent to the burn, and the activity was dominated by much slower contractions than control. No direction of vessel diameter changes prevailed uniformly throughout the peripheral microcirculation. Large alternate constrictions and dilations were also observed for some arteriolar and venular components, but others exhibited no significant change at all. The incidence and magnitude of peripheral microvascular response was proportional to the size of the injured area.

Fluctuations in the diameter of selected arterioles in the cutaneous microcirculation of Syrian golden hamster dorsal skin flap chambers, which ranged in size from 10 to 70 microns at different branching order sites, were measured before burn, at the same sites after burn and after injection of the drug. Three different drugs epinephrine (administered intravenously), ibuprofen (administered intravenously), and tetrachlorodecaoxide (administered intravenously and topically) were evaluated. Results show that the response to thermal injury in the control group involved extensive vasodilation in the arterioles, prolonged flow irregularities including flow obstructions and stasis, and a decrease in the level of vasoactivity of the microvessels. In two treatment groups, the ibuprofen and tetrachlorodecaoxide groups, significant improvement as indicated by reduced vasodilation and edema and improved microcirculatory blood flow after injury were observed. Further testing of tetrachlorodecaoxide as a topically applied wound dressing is indicated.

A rise in plasma triglycerides has been noted after thermal injury in a number of animal species including humans. In this study we identified a factor, tumor necrosis factor, which was responsible for increased plasma triglycerides during thermal injury that was induced by scalding. Two strains of mice that differed genetically in susceptibility to lipopolysaccharides were used. These were CH3HEB/HeJ (LPS-) and CH3HEB/FeJ (LPS+). A 15% total body surface area was burned; this resulted in an increase of plasma triglycerides of 126% of preburn levels in the LPS+ strain 24 hours after burn injury. No change in triglycerides was noted in the LPS- mice at any time after burn injury. Sera from LPS+ mice at 1 to 2 hours after burn injury was injected into nonburned animals of the same strain; this caused a 62% +/- 5% increase in plasma triglycerides 24 hours after injection. When thermally injured LPS+ mice were injected with anti-tumor necrosis factor-alpha at 1 hour after injury, they did not show a rise in plasma triglycerides at any time between 24 to 72 hours after injury. Hepatic secretion of triglycerides was also measured 1 day after burn; the average secretion of triglycerides was significantly reduced (2.69 +/- 0.36 mg/kg/hr, compared with 3.83 +/- 0.15 mg/kg/hr for the control). We conclude that tumor necrosis factor, a cytokine that inhibits lipoprotein lipase, causes hypertriglyceridemia during thermal injury in spite of a decreased secretion of triglycerides. This is the first report that demonstrates that hypertriglyceridemia that is secondary to thermal injury is induced by tumor necrosis factor.

Burn treatment requires large volumes of crystalloid, which may exacerbate burn-induced cardiopulmonary dysfunction. Small-volume hypertonic saline dextran (HSD) resuscitation has been used for effective treatment of several types of shock. In this study isolated coronary perfused guinea pig hearts were used to determine if HSD improved left ventricular contractile response to burn injuries. Parameters measured included left ventricular pressure (LVP) and maximal rate of LVP rise (+dP/dt max) and fall (-dP/dt max) at a constant preload. Third-degree scald burns comprising 45% of total body surface area (burn groups, N = 75), or 0% for controls (group 1, N = 25) were produced using a template device. In group 2, 25 burned guinea pigs were not fluid resuscitated and served as untreated burns; 20 burns were resuscitated with 4 mL lactated Ringer's (LR) solution/kg/% burn for 24 hours (group 3); additional burn groups were treated with an initial bolus of HSD (4 mL/kg, 2400 mOsm, sodium chloride, 6% dextran 70) followed by either 1, 2, or 4 mL LR/kg/% burn over 24 hours (groups 4, 5, and 6, respectively). Untreated burn injury significantly impaired cardiac function, as indicated by a fall in LVP (from 88 +/- 3 to 68 +/- 4 mmHg; p = 0.01) and +/- dP/dt max (from 1352 +/- 50 to 1261 +/- 90 and from 1150 +/- 35 to 993 +/- 59; p = 0.01, respectively) and a downward shift of LV function curves from those obtained from control hearts. Compared to untreated burns, hearts from burned animals treated with LR alone showed no significant improvement in cardiac function. However hearts from burned animals treated with HSD + 1 mL LR/kg/% burn had significantly higher LVP (79 +/- 4 vs. 68 +/- 4 mmHg, p = 0.01) and +/- dP/dt max (+dP/dt: 1387 +/- 60 vs. 1261 +/- 90 mmHg/sc, p = 0.01; -dP/dt: 1079 +/- 50 vs. 993 +/- 59 mmHg/sc, p = 0.01) than hearts from untreated burned animals and generated left ventricular function curves comparable to those calculated for hearts from control animals. Mortality 24 hours after burn was 29% for untreated burns was 0% for control animals, as well as for groups treated with the Parkland formula or HSD plus 1 or 2 mL/kg/% burn lactated Ringer's. The only deaths after treatment occurred in those animals given HSD plus 4 mL/kg/% burn, Parkland formula (17% mortality).(ABSTRACT TRUNCATED AT 400 WORDS)

Lipid mobilization following thermal injury was studied in 25 patients with burns of between 35 and 95% TBSA for 30 to 50 days postinjury. The concentration of free fatty acids and glycerol in the plasma was elevated. The concentration of plasma triglycerides was elevated, while the concentration of ketone bodies remained normal. Thus it is suggested that the free fatty acids are primarily being re-esterified to triglycerides rather than being utilized for ketone body production. During the first 10 days postinjury, the plasma carnitine level was slightly decreased, while the concentration of carnitine in liver and muscle was elevated. The level of carnitine in burn wound fluid was similar to that in plasma. Therefore, the early decrease in plasma carnitine appeared to result from wound losses, as well as the sustained increased uptake by liver and muscle throughout the burn course.

In the present investigation, we found that the catechol-O-methyltransferase activity (COMT) in erythrocytes of persons with severe thermal injury was strikingly increased when compared with that in erythrocytes of noninjured individuals. The specific activity of COMT in erythrocytes of burned patients was not correlated with extent of burn. Thus the echinocytes of burned persons are another example of abnormal red cells in which COMT activity is increased. This appears to be the first example of increased COMT activity in abnormal erythrocytes that is not associated with large numbers of reticulocytes.

A prospective evaluation of several techniques used to monitor thermally injured patients for septic complications was initiated. Thirty-eight extensively burned patients, at high risk for septic complications, were selected for study. Of these, 92% developed significant burn wound infection. Careful daily clinical evaluation and serial quantitative burn wound biopsy cultures provided the most effective means of establishing an early diagnosis of would sepsis. Serial blood cultures performed by the two different techniques were of very limited value in the recognition were not recovered until 5-10 days following documentation of heavy bacterial colonization of the burn wound.

In a study of 27 thermally burned patients (mean TBSA, 58%; range, 32-96%) serum fibronectin levels were decreased with parallel decreased oxygen consumption of stimulated peripheral blood phagocytes and decreased EGTA-blocked burn serum opsonizing activity which correlated with serum fibronectin changes postburn. Normal and burn sera fibronectin content also correlated with the opsonizing times for zymosan and Staphylococcus aureus but not for Enterobacteriaceae. Although in vivo 14 cases showed circulating fibronectin 140 micrograms/ml or lower and a marked decrease in Staphylococcus aureus opsonization, only two patients from this group revealed positive Staphylococcus aureus blood cultures and serum fibronectin levels were higher in patients with Staphylococcus aureus sepsis than in patients with Enterobacteriaceae sepsis. Supplementary experiments on leukocyte oxidative response after zymosan stimulation in normal, fibronectin-depleted, and fibronectin-reconstituted serum demonstrated that the lag period of oxygen burst is a fibronectin-dependent reaction.

Rapid closure of burn wounds significantly reduces the complications associated with thermal injury. Successful wound coverage, however, is often limited by the lack of suitable autografts. To circumvent this limitation a composite graft was developed which combines the utility and availability of allogeneic skin with the permanence of an autograft. Composite grafts were first employed in a rat wound model and subsequently to treat six patients with thermal injuries. In experiments with rats, full-thickness excised (1") wounds were prepared on thoracic walls, covered with previously frozen allograft skin, dressed, and secured. Five days later, the dead epidermis was removed and trypsin-disaggregated syngeneic epidermal cells applied to the exposed dermal surface. Successful engraftment with complete epidermal coverage could be observed within 7 to 10 days. In eight patients, split-thickness skin bank allografts were placed on full-thickness burn wounds. Four days later the dead epidermis was removed and vacuum blister-prepared sheets of autologous epidermis grafted to the exposed dermal surface. In all eight patients successful engraftment ensued. Increased pigmentation at the site of each original epidermal graft confirmed the stability of underlying allograft dermis. Epidermal expansion ranged from 1:20 to 1:100. All patients were followed from 10 to 12 months with no demonstrated graft loss or significant wound contracture. Composite skin grafts which combine allogeneic dermis and an expanded autologous epidermis can effect rapid wound closure and will remain stable without evidence of rejection or graft breakdown for at least 12 months.

The influence of thermal injury on adrenal secretion of dehydroepiandrosteron sulfate (DS) and cortisol was investigated in 19 adult patients. We found that within the first 5 days after burn trauma serum levels of DS were reduced to about one third the concentration in 21 similarly aged, nonstressed adults; serum cortisol levels in burned subjects were increased twofold over control levels. Serum DS levels were progressively lower, whereas serum cortisol concentrations remained relatively constant in burned patients between 6 and 55 days postburn. These data demonstrate prolonged alterations in adrenal steroid production after thermal injury and are suggestive that adrenal androgen production is, at least in traumatized subjects, regulated by factors other than ACTH.

The release of oxygen free radicals from ischemic myocardium has been implicated as a causative factor of cardiac dysfunction after thermal injury. In this study, isolated coronary perfused guinea pig hearts were used to determine if free radical scavengers improve left ventricular (LV) intrinsic contractile response to burn shock. Parameters measured included peak isovolumic LV pressure (LVP) and maximal rate of LVP rise (+dP/dtmax) and fall (-dP/dtmax) at a constant preload. Control animals were immersed in body temperature water and divided into four groups: Group 1, untreated N = 10; Group 2, control animals treated with unbound superoxide dismutase (SOD), N = 5; Group 3, control animals treated with ficoll-SOD, N = 5; and Group 4, control animals treated with PEG-SOD, N = 5. Scald burn equivalent to 45% of total body surface area was produced in 64 animals. Fluid resuscitation was initiated immediately after burn in all animals, and animals were then divided into seven burn experimental groups. In Group 5, 10 animals were treated with fluid alone, lactated Ringer's, 4 mL/kg/% burn. Burned animals in Group 6 (N = 10) received a reduced volume of Ringer's 2 mL/kg/% burn plus unbound-SOD, 50 mg/kg; 10 animals in Group 7 received this volume of Ringer's plus ficoll-SOD, 50 mg/kg. In groups 8, 9, and 10 animals were given fluid, lactated Ringer's, 2 mL/kg/% burn plus varying doses of PEG-SOD (Group 8: N = 9, 1,000 U; Group 9: N = 10, 6,000 U; Group 10: N = 5, 12,000 U). In Group 11 (N = 10), animals received SOD-PEG, 6,000 U, plus catalase, CAT-PEG, 6,000 U, given with 4 mL/kg/% burn lactated Ringer's solution. Hypotension, hypothermia, and hemoconcentration were similar in all animals after thermal injury, regardless of treatment regimen. Burn hearts showed significantly lower LVP, +dP/dt max, and -dP/dt max than control hearts (P less than 0.05). Compared to controls, coronary pressure and coronary vascular resistance were significantly higher in all treated burn groups. There was no significant difference in heart rate or time to peak pressure or time to maximal contraction or relaxation among the groups. Left ventricular function curves for burned hearts were shifted downward and to the right of curves obtained from control hearts (P less than 0.01), regardless of scavenger treatment. PEG-SOD, 6,000 U, improved left ventricular contractility (+dP/dt) at maximal levels of end-diastolic pressure but deficits in left ventricular pressure and relaxation persisted.(ABSTRACT TRUNCATED AT 400 WORDS)

Of the several tests which measure leukocyte bactericidal competency only one, chemotaxis, has been reported to reflect both leukocyte dysfunction and patient mortality in major thermal injury. To validate the reliability that chemotaxis reflects mortality functional chemotactic index (FCI) was measured in leukocytes from 33 patients with 30% or greater total body surface area burns. Additionally, nitroblue tetrazolium (NBT) reduction and O2 consumption were compared to FCI. Significant decreases were seen in FCI values compared to normals. No differences, however, were seen in FCI values between surviving and nonsurviving patients. NBT reduction and O2 consumption also showed decreases with a significant difference between the mean decrease in surviving and nonsurviving patients. While the data show all these laboratory tests to be reflective of significant impairments in host defense, they do not appear to be reliable as predictive indices of patient survival and therefore should not be interpreted as such.

Radioimmunoassays for 5(S), 12(R)-dihydroxyeicosa-6, 14-cis, 8,10-trans-tetraenoic acid (leukotriene B4, LTB4) and 5(S)-hydroxy-6(R)-L-gamma-glutamyl-L-cysteinyl-glycinyleicosa-7,9- trans, 11,14-cis-tetraenoic acid (leukotriene C4, LTC4) have been used to quantify the concentrations of these arachidonic acid metabolites in plasma (12 patients) and blister fluid (6 patients) of burned patients. The results of this study demonstrate that, in general, burn plasma LTB4, and LTC4 were not elevated; however, in individual cases, transient high levels of leukotrienes were observed. Correlation between leukotriene "peaks" and the clinical course could not be established. High levels of LTB4 and LTC4 in burn blister fluid suggest their participation in local inflammatory reactions.

These studies establish that the staphylococcal clumping test is superior to the tanned red cell hemagglutination inhibition immunoassay for monitoring fibrin split product concentration in burn sera. It is strongly suggested that the principal circulating degradation product is a complex of soluble fibrin monomer with fragment D. Finally, there does not appear to be any effect on measured fibrin split product concentration in sera of burn patients receiving prophylactic heparin or aspirin.

Irreversible sepsis, in spite of advancements in topical therapy and antimicrobial agents, remains the leading cause of death in major thermal injury. A defect in intracellular bactericidal capacity in leukocytes from severely burned patients appears to correspond with increases in bacterial wound colonization and ultimate sepsis. This leukocyte defect has been demonstrated by abnormally low nitroblue tetrazolium reduction (NBT) and oxygen consumption of white cells in patients with major thermal injury. The subcellular mechanisms responsible for decreased bactericidal capacity were therefore investigated. Nicotinamide-adenine dinucleotide (NADH) and nicotinamide-adenine phosphodinucleotide (NADPH) oxidase activity was measured in patients with major burns, controls (normals), and in patients with nonburn stress or infection. NADH and NADPH oxidase levels in leukocytes from burn patients were not significantly different from those of normal nonchallenged controls but were significantly lower than the leukocyte values found in the patients with nonburn infections or stress. This NADH and NADPH defect in the subcellular leukocyte fraction suggests that it may be a significant factor in the reduced bactericidal function of the intact leukocyte in thermally injured patients.

The anemia of thermal injury is characterized by a decreased RBC half-life and abnormal RBC morphology (predominantly echinocytes). These changes are reversible in crossover studies with normal recipients, suggesting an extrinsic mechanism unrelated to initial heat or mechanical damage. Since alterations in plasma lipids, which are freely exchangeable with red cell lipids, produce similar changes, plasma and erythrocyte membrane lipid composition in 30 patients (mean 60% TBSA) was determined and related to RBC morphology in vivo and in vitro. Total cholesterol (TC) and phospholipids (PL) were decreased in plasma and plasma lipoproteins (LP) but remained normal in red blood cell membranes. The deficit in TC and LP cholesterol resulted from decreased cholesterol esters. Plasma phospholipids contained increased phosphatidylcholine (PC) and low lysophosphatidylcholine (LPC) and sphingomyelin levels. The essential fatty acid (EFA) composition of total plasma lipids rapidly decreased, with a more gradual decrease in EFA in red cell lipids. The ratio of free fatty acids to albumin in the plasma was greatly increased throughout and may have a primary role in the abnormal erythrocyte morphology and decreased half-life in burned patients.

A case of liquid propane cold injury is described. This injury was produced by evaporative heat loss, without ignition, from skin and underlying tissues. The cutaneous appearance was that of a flame burn but underlying deep tissue damage was present. Acute vascular compromise and progressive wound sepsis were complications which required surgical intervention. A liquid propane animal model was created which defined the pathophysiology of the clinical injury. The potential for this injury exists wherever volatile liquified gases are used.

Burns received as a result of motor vehicle accidents (MVA's) create special problems in their care, as they are frequently severe and are often associated with other injuries. One hundred seventy-eight consecutive patients with burns sustained in an MVA were studied. The mean TBSA burn was 33.9%. The mortality was 24.7%, but the mean burn size in this fatal group was almost doubled at 63.9%. The injury most commonly associated with death was inhalation injury (in 36.3%). Thirty-six per cent of the patients sustained other injuries in addition to their burn, the most frequent of which was to the musculoskeletal system (67 injuries). Multiple trauma had little effect on mortality unless severe, but fractures especially complicated burn wound care unless surgically stabilized. Current methods of management are presented along with our approach to multiply injured burn patients.