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1 Department of Plastic and Reconstructive Surgery, Tokyo Women's Medical College, Tokyo, Japan; and Departments of 2 Pediatrics, 3 Anesthesiology and Physiology and Biophysics, and 4 Pathology, The University of Texas Medical Branch, and Shriners Burns Institute, Galveston Texas 77555-0823
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ABSTRACT |
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 TOP
 ABSTRACT
 INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
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The effects of a
monoclonal antibody against L-selectin [leukoctye adhesion
molecule (LAM)1-3] on microvascular fluid flux were
determined in conscious sheep subjected to a combined injury of 40%
third-degree burn and smoke inhalation. This combined injury induced a
rapid increase in systemic prefemoral lymph flow
(s
lymph) from the burned area and a delayed-onset increase in lung lymph flow.
The initial increase in
slymph was
associated with an elevation of the lymph-to-plasma oncotic pressure
ratio; consequently, it leads to a predominant increase in the systemic
soft tissue permeability index (sPI). In an untreated control group,
the increased sPI was sustained beyond 24 h after injury. Pretreatment
with LAM1-3 resulted in earlier recovery from the increased sPI,
although the initial responses in
slymph and sPI
were identical to those in the nontreatment group. The delayed-onset
lung permeability changes were significantly attenuated by pretreatment
with LAM1-3. These findings indicate that both leukocyte-dependent
and -independent mechanisms are involved in the pathogenesis that
occurs after combined injury with burn and smoke inhalation.
systemic prefemoral lymph; lung lymph; fluid balance; hemodynamics; sheep
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INTRODUCTION |
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TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
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THERMAL INJURY GREATLY ALTERS microvascular fluid flux at the injury site. In patients with a large body surface area burn, this "capillary leak" leads to an intravascular volume depletion, rapidly requiring a large amount of fluid for resuscitation. Additional smoke inhalation induces further hemodynamic instability and increases fluid requirements (9, 35, 45). It is well known that both thermal injury and smoke inhalation involve inflammatory processes, although the details of pathogenesis and the time course for development of physiological manifestations are different (44).
Leukocytes, particularly polymorphonuclear neutrophils (PMNs), are
central mediators of inflammatory processes and play a significant role
in the pathogenesis of both thermal injury (29, 34) and smoke
inhalation (5). Endothelial injury by activated PMNs is thought to
occur as a result of the release of proteases and toxic oxygen
products, leading to increases in microvascular permeability and edema
formation. The selectin family of adhesion-promoting molecules,
including L-, E-, and P-selectins, appears to be involved in the
earliest events of the acute inflammatory processes. The initial
adhesive interactions between PMNs and endothelial cells (ECs) by the
selectin family result in the "rolling" phenomenon, whereby PMNs
assume an intermittent adhesive contact with ECs (2, 11). The second
phase for the firm adhesive interaction appears to depend on engagement
of the 
2-integrins (CD11/CD18) on the PMNs and the intracellular adhesion molecule (ICAM)-1 or ICAM-2
on the ECs (42).
Because the rolling phenomenon is the first step of adhesion, it seems reasonable to consider an immunoneutralization of the selectin family as a potentially therapeutic intervention for patients with severe thermal injury. Accumulating experimental evidence suggests that the inhibition of selectins reduces PMNs' accumulation into the tissues and permeability changes, not only in the local burned skin but also in distant organs, including the lung (19, 34, 38). Within this paradigm, one might expect that reduced endothelial injury by inhibition of PMN-EC adherence might cause significantly less fluid loss and consequently an early establishment of hemodynamic stability after severe thermal injury. However, only a few studies (30) have examined physiological manifestations to determine the effect of inhibition of the PMN-EC interactions.
Accordingly, the present study was undertaken to test the effect of an anti-L-selectin antibody [leukocyte adhesion molecule (LAM)1-3] on physiological manifestations after severe thermal injury. Of particular interest were alterations in the microvascular fluid flux in both burned tissue and lung. L-selectin was chosen as a therapeutic approach, as selectins located on the ECs (P- and E-selectin) exhibit organ-specific differences in their pathophysiological relevance (19, 33). We used a combined-injury model with 40% body surface area (BSA), third-degree burn, and 48 breaths of cotton smoke inhalation to mimic the hemodynamic alterations often seen in patients with severe burn injury.
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MATERIALS AND METHODS |
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TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
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Animals were cared for in the Ovine Intensive Care Unit at our institution (Univ. of Texas Medical Branch), which is approved by the American Association of Laboratory Animal Care. The experimental procedures were approved by the Animal Care and Use Committee of The University of Texas Medical Branch. The National Institutes of Health and American Physiological Society guidelines for animal care were strictly followed. Animals were studied in the awake state.
Antibody development and testing. Purified LAM1-3 (47), a murine monoclonal anti-human L-selectin antibody that interferes with PMN attachment to human umbilical vein ECs, was obtained from Xenotech (San Mateo, CA). Each lot of antibody was tested by the Limulus assay (24) and was free of endotoxin.
Before this study, we performed an in vitro study to ensure the ability of this antibody to block adherence of ovine neutrophils to ECs. Ovine neutrophil attachment to ECs was examined, as previously described for human neutrophils (27), with the following modifications. Briefly, sheep vena cava ECs were grown to confluence in eight-well tissue culture Lab-Tek chambers or on slides (Miles, Naperville, IL). The cells were stimulated with interleukin (IL)-1
(167 pg/ml) for 6 h.
The cells were brought to 4°C just before the adherence reactions
to eliminate adherence secondary to CD18. Fresh sheep neutrophils (3.4 × 105) at 4°C were
added to the wells with or without LAM1-3 (100 µg/ml) in a final
volume of 200 µl. The cells were allowed to adhere under static
conditions for 15 min. At the end of this time, the chambers were
placed on a rotating platform at ~75 rpm for 15 min. The wells were
gently washed twice with buffer, and the cells were fixed in
paraformaldehyde and counted. The number of neutrophils adhering to the
stimulated sheep endothelium with LAM1-3 (normalized to 100%
binding for cells without antibody) was 31 ± 6 (SE) %. These
values for LAM1-3 are similar to that found for human ECs and
neutrophils (27), ensuring the functional cross-reaction of LAM1-3
to the ovine neutrophils.
Surgical preparation. Twenty-one female range-bred adult sheep (32-42 kg) were surgically prepared for study. All animals were intubated via an endotracheal tube and ventilated during the surgery while under halothane anesthesia. Arterial and venous catheters (16 G, 24 in., Intracath, Becton-Dickinson, Sandy, UT) were placed in the descending aorta and inferior vena cava via the femoral artery and vein, respectively. A Swan-Ganz thermal dilution catheter (model 93A-131-7F, Edwards Critical Care Division, Irvine, CA) was positioned in the pulmonary artery via the right external jugular vein. The chest was opened at the fifth intercostal space on both sides, and an efferent lymphatic from the caudal mediastinal lymph node was cannulated (Silastic medical-grade tubing, 0.025 in. ID, 0.047 in. OD, Dow Corning, Midland, MI) by a modification of the technique of Staub et al. (48). The systemic contribution was removed by ligation of the tail of the caudal mediastinal lymph node and cauterization of the systemic diaphragmatic lymph vessels. A Silastic catheter was also positioned in the left atrium to measure left atrial pressure directly. An incision was made anterior to the right tensor fascia lata, and an efferent lymphatic from the systemic prefemoral lymph node was cannulated by using the method of Demling et al. (10). The sheep were given 5-7 days to recover from the surgical procedure with free access to food and water.
Burn and smoke inhalation injury. Before the injury was produced, all animals received a tracheotomy and a cuffed tracheostomy tube (10-mm diameter, Shiley, Irvine, CA) was inserted by using 10 mg/kg of ketamine (Ketalar, Parke-Davis, Morris Plains, NJ). Then, the anesthesia was continued with 2-3% halothane and 50% oxygen. Sixteen sheep then received a combined injury with a 40% third-degree burn and 48 breaths of cotton smoke inhalation. After the wool over the bilateral flank was shorn, a 20% total body surface third-degree flame burn was given to the flank of one side. The BSA was calculated from the equation BSA = 0.084 × body wt (kg)2/3 (12). Burn was produced with a Bunsen burner, until the skin was thoroughly contracted. We have previously determined this degree of injury to be a full-thickness burn, i.e., including both epidermis and dermis, in which the nerve endings are heat destroyed (7). Thereafter, inhalation injury was induced while the sheep was in the prone position. A modified bee smoker was filled with 50 g of burning toweling and was connected to the tracheostomy tube. The connection contained a thermistor to monitor the temperature of the smoke. During the insufflation procedure, the temperature of the smoke did not exceed 40°C. The sheep were insufflated with 48 breaths (650 ml/breath) of cotton smoke. The details of the smoking procedure and the chemical composition of the smoke have been previously described (26). After smoke insufflation, another 20% BSA third-degree burn was given to the flank of the other side. A Foley catheter was placed in the bladder to determine urine output. During this procedure, ~30 min of anesthesia were required.
Experimental protocol. On the day of the injury, baseline measurements were obtained. Two hours before injury, seven sheep (LAM1-3 group) received LAM1-3 (1.0 mg/kg body wt dissolved in 10 ml 0.9% NaCl) as a bolus intravenous injection. Adequate concentrations of LAM1-3 at 48 and 72 h were documented by using flow cytometry to demonstrate that the L-selectin on normal neutrophils (1 × 106 cells/ml) placed in plasma from these animals was completely saturated. Nine animals (nontreatment group) did not receive this treatment. All 16 animals were given the combined injury with 40% third-degree burn and 48 breaths of cotton smoke described in the previous subsection. Five animals (control group) underwent the same procedure, including the tracheostomy and anesthesia, but did not receive any injury. Immediately after these procedures, anesthesia was discontinued and physiological measurements were serially determined at 3, 6, 12, 18, 24, 36, 48, and 72 h after insult, while all animals were resuscitated after the protocol described in the following subsection.
Resuscitation protocol. Immediately after injury, anesthesia was discontinued and the animals were allowed to awaken but were mechanically ventilated with a Servo Ventilator 900C (Siemens-Elena, Solna, Sweden) throughout the next 72-h experimental period. Ventilation was performed with a positive end-expiratory pressure of 5 cmH2O and a tidal volume of 15 ml/kg. The respiratory rate was set to maintain normocapnia. For the first 3 h after the combined injury, all animals received 100% inspiratory oxygen concentration; thereafter, the setting was adjusted to maintain the arterial oxygen saturation above 90%. These respiratory settings allowed a rapid disappearance of carboxyhemoglobin after smoke inhalation (26).
Fluid resuscitation during the experiment was performed with Ringer lactate solution following the Parkland formula (6) (4 ml · %burned surface area
1 · kg
body wt1 for the first
24 h and 2 ml · %burned surface
area1 · kg
body
wt1 · day1
for the next 48 h). One-half of the volume for the first day was
infused in the initial 8 h, and the remainder was infused in the next
16 h. Urine was collected, and urine output was recorded every 24 h.
Fluid balance was determined by urine output every 24 h subtracted from
total fluid volume infused and was represented as
ml · kg1 · day1.
During this experimental period, the animals were allowed free access
to food, but not to water, for determination of accurate fluid balance.
Because the resuscitation protocol itself might affect the
physiological parameters, even the animals in the control group received the identical amount (ml/kg body wt) of fluid resuscitation and underwent the same ventilatory support as injured animals during
the whole experimental period. When all measurements were completed,
all animals were anesthetized with ketamine and humanely killed by
administration of a saturated potassium chloride solution.
Hemodynamic and oxygenation variables. Measured physiological parameters were not considered valid until the animals were fully awake and standing. Hemodynamic and oxygenation variables were measured and calculated according to standard formulas. Cardiac output was measured with a cardiac output computer (model 9520, American Edwards) by the thermodilution method with 5% dextrose as an indicator solution, then divided by BSA to determine the cardiac index (CI). Vascular pressures were measured by using fluid-filled pressure transducers (P23ID, Statham Gould, Oxnard, CA) adapted to a continuous flushing device and connected to a physiological recorder (model OM9 patient monitor, Electronics for Medicine, Honeywell, Pleasantville, NY). Zero calibrations were taken at the level of the olecranon joint on the front leg, which is considered to be the level of the right atrium. At every time point, arterial and mixed venous blood were determined (models 1302 pH/blood-gas analyzer and 282 CO-oximeter, Instrumentation Laboratory, Lexington, MA). The blood-gas results were corrected for the body temperature of the sheep.
Lymph and plasma measurements.
Systemic prefemoral lymph flow
(slymph)
and lung lymph flow
(Llymph)
were measured with a graduated test tube and stopwatch. Lymph and blood
samples were collected in EDTA tubes, and then the colloid osmotic
pressure in plasma (
p),
systemic prefemoral lymph
(si), and lung lymph
(i,L)
were determined through a semipermeable membrane in a colloid osmometer
(model 4100, Wescor, Logan, UT). Systemic permeability index (sPI) and
lung permeability index (PI,L)
were calculated according to the following equations
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Analysis of data. All values are reported as means ± SE. Outcome variables for physiological parameters were analyzed by using analysis of variance for a two-factor experiment with repeated measures on time. The two factors are experimental groups (control, nontreatment, and LAM1-3 group) and time (9 time points, including baseline). Fluid balance data for each day were analyzed by using one-way analysis of variance. Fisher's least-significant-difference procedure was used for multiple comparisons, with Bonferroni correction for number of comparisons. All tests were assessed at the 0.05 level of significance.
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RESULTS |
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TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
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Two of nine animals in the nontreatment group and one of seven animals
in the LAM1-3 group did not survive the entire experimental protocol. The survival time after injury of these three animals was 48, 60, and 68 h, respectively. The CI was 7.80, 8.24, and 7.04 l · min1 · m2,
respectively, immediately before death. On the other hand, the arterial
PO2-to-inspiratory oxygen fraction
ratio (P/F) was 59, 52, and 65 Torr, respectively, indicating that the
major cause of death was due not to cardiopulmonary dysfunction by
inadequate fluid resuscitation but to progressive deterioration in
oxygenation. The data from these three animals were discarded from
further analysis. All other animals survived the 72-h experimental
period, with normal appetite and intake of food.
All animals received an identical amount of fluid infusion after the
Parkland formula, which was applied to the 40% BSA thermal injury.
Without any injury, the control group exhibited an intake-dependent urine output (Fig. 1). The animals that
received the combined injury (the nontreatment group and the
LAM1-3 group) showed significantly less urine output than did the
control group in the first and second days after injury. During the
first day, urine output in the LAM1-3 group was significantly
higher than in the nontreatment group.
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The summarized cardiopulmonary hemodynamic data are shown in Table
1. After the combined injury with burn and
smoke inhalation, there was a transient decrease in CI, whereas the
control group did not show any significant alterations during the whole
experimental period. The decreased CI in the nontreatment group and
LAM1-3 group gradually returned toward baseline values, and at 72 h after injury it was increased from the baseline value. Despite the
initial decrease in CI, mean arterial pressure was maintained in both nontreatment and LAM1-3 groups. Pulmonary arterial pressure was increased in all groups under mechanical ventilation with positive end-expiratory pressure. There was no statistically significant difference between the nontreatment and the LAM1-3 groups in
hemodynamic variables at any time.
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Table 2 depicts the oxygenation data in
both groups. The arterial blood PO2
was well maintained in all groups with ventilatory support.
Progressively deteriorating oxygenation in the injured animals was
represented as a significant decrease in the P/F 12 h after the
combined injury with burn injury and smoke inhalation. There was no
statistical difference between the nontreatment group and the
LAM1-3 group in these oxygenation parameters.
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p,
si, and
i,L
are shown in Table 3. After combined
injury, p rapidly decreased in
the nontreatment and the LAM1-3 groups. Lymph oncotic pressures
also gradually decreased in both injured groups. However, during the
initial 12 h the decrease in si
was not significantly different from the baseline values of these two
groups.
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Systemic soft tissue (burned tissue in the nontreatment and the
LAM1-3 groups) microvascular fluid flux is shown in Fig.
2. After injury, there was a rapid increase
in slymph in
both nontreatment and LAM1-3 groups. This increase was accompanied
by a transient increase in lymph-to-plasma oncotic pressure ratios;
consequently, sPI was significantly increased immediately after injury.
In the control group, there was a mild but significant increase in the slymph, with a
large amount of fluid infusion. However, this increase was associated
with a transient decrease in the
si/p; therefore, in the control group sPI was essentially unchanged during
the whole experimental period. Increased sPI in both the nontreatment
group and the LAM1-3 group subsided 72 h after injury. The peak of
the increased sPI, however, seems to be different between the two
groups; in the nontreatment group, increased sPI was sustained more
than 24 h after injury, whereas that in the LAM1-3 group began to
subside earlier, creating a significant difference at 48 h after
injury.
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Figure 3 depicts the pulmonary
transvascular fluid flux. In the nontreatment group, a significant
increase in
Llymph
was noted 12 h after injury. This increase was significantly attenuated by pretreatment with LAM1-3. In contrast to the burned tissue lymph,
i,L/p
was virtually unchanged during the whole experimental period in all
groups. Consequently, increased
PI,L after the combined injury
was significantly attenuated by the pretreatment with LAM1-3 at 24 h after injury.
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DISCUSSION |
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TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
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Because we wished to determine the role of L-selectin on physiological manifestations in the severe thermal injury model, reproducible hemodynamic responses to injury are essential in this study. It is well known that hemodynamic responses to thermal injury in the acute phase and those in the postresuscitation phase are totally different (53) and are significantly modified by fluid resuscitation regimens (32). In the present study, the Parkland formula for fluid resuscitation, which is most widely accepted among multiple institutions (13), was strictly followed during the whole experimental period. Animals that were subjected to the combined injury with 40% third-degree burn and severe smoke inhalation exhibited a biphasic hemodynamic response. The initial hemodynamic change was characterized as a decrease in CI, whereas the mean arterial pressure was easily maintained by fluid resuscitation. Thereafter, CI gradually increased toward baseline value and exceeded it at 72 h after injury. These findings are commonly observed in patients with severe thermal injury (53).
Most of these hemodynamic alterations might be attributable to
increased microvascular fluid flux in the burned tissue and subsequent
fluid shift from the vascular space to the interstitial space. This
capillary leak was manifested as a rapid increase in
slymph,
si/p,
and sPI. Pretreatment with LAM1-3 did not show any effect on these
alterations, suggesting that microvascular changes immediately after
thermal injury were not L-selectin dependent. A number of mediators,
such as histamine (17), bradykinin (41), serotonin (15), prostaglandins
(4), and leukotrienes (3), may contribute to rapid permeability changes
after thermal injury. Toxic oxygen products also play a major role in
local permeability changes after thermal injury, because antioxidant
enzymes, such as catalase or superoxide dismutase, attenuate early
edema formation in thermally injured animals (51). The source of these
reactive oxygen intermediates remains unclear. Not only microvascular
permeability but also physical alterations in the interstitial space
contribute to the rapid increase in fluid flux. Lund et al. (28)
demonstrated strongly negative hydrostatic pressure in the dermal
interstitium immediately after thermal injury. Data from the present
study are compatible with previous observations indicating that initial burn edema formation does not require the presence of PMNs.
Despite an inability to attenuate the initial transvascular fluid flux
in the burn wound, the anti-L-selectin antibody seems to have an effect
on burned tissue permeability in the later period after burn. The
increased sPI in the nontreatment group was sustained beyond 24 h after
injury, whereas that in the LAM1-3 group began to subside before
24 h. Mulligan et al. (34) used a second-degree thermal injury model in
rats and reported that neutrophil depletion reduced edema formation 4 h
after thermal injury but did not reduce it 1 h after injury. In their
report (34), a monoclonal antibody against L-selectin also attenuated
edema formation in burned skin 4 h after injury. The findings in the
present study are in accordance with their reports (34), suggesting
that neutrophil-dependent edema formation does not occur immediately
but in the later period after thermal injury. A large discrepancy in
the time scale for developing neutrophil dependency [i.e., 4 h
after injury in the study by Mulligan et al. vs. more than 24 h after
injury in the present study] might be the result of different
injury models between the two studies. Rapid hyperemic changes are
consistent findings in second-degree burn wounds (16, 39). On the other hand, large third-degree burns induce significant decreases in blood
flow to the burn wound (14). Systemic hemodynamic alterations associated with larger burns may accentuate this low-perfusion state in
the burned tissue. An initially decreased vascular bed available for
adherence in third-degree burn might be related to the later
involvement of neutrophils in the present study. With respect to the
pathogenesis inducing permeability changes, there appears to be a
distinct difference between thermal injury and smoke inhalation. In
contrast to the immediate alterations in burn wound permeability, lung
edema associated with smoke inhalation is generally delayed in onset
(23, 40, 44). This distinct difference was consistently reproduced in
the present combined-injury model. In the nontreatment group, a
significant increase in
Llymph was observed more than 6 h after injury. In addition,
i,L/p was virtually unchanged, whereas
si/p
was transiently increased after injury. Therefore, a significant
increase in PI,L was also noted more than 6 h after injury.
Toxic oxygen products are involved in these delayed-onset pulmonary microvascular derangements (25, 36). We have previously shown that depletion of the PMNs from sheep virtually eliminated the pulmonary permeability changes seen after smoke inhalation (5). On the other hand, inhibition of xanthine oxidase (XO), another source of oxygen radicals, does not attenuate lung fluid flux after smoke inhalation (1), whereas XO inhibitors are reported to reduce rapid edema formation in burn wounds (51). These observations suggest the source of oxygen free radicals after smoke inhalation may be different from that in the acute burn wound. In the present study, immunoneutralization of L-selectin significantly attenuated the increase in pulmonary vascular permeability. This finding supports previous observations indicating that PMNs play a central role in delayed-onset pulmonary microvascular derangements after smoke inhalation.
Although LAM1-3 reduced the delayed-onset pulmonary microvascular permeability changes, it did not attenuate the oxygenation deficit in this combined-injury model. The mechanisms by which the progressive hypoxia occurred after smoke inhalation are complicated and are not fully explained by the alveolar phenomenon secondary to increased pulmonary microvascular permeability. In the present study, recovering pulmonary microvascular permeability 48-72 h after injury did not induce improvement in oxygenation in either nontreated or treated groups. Bronchiolar phenomena, such as bronchospasm, peribronchial constriction, or partial bronchial obstruction by cast formation, also contribute to the progressive hypoxia (20, 52). A recent investigation using the multiple-inert-gas elimination technique (46) demonstrated that pulmonary blood flow was recruited to the low ventilation-perfusion compartment at 24-72 h after smoke inhalation. Therefore, mechanisms other than increased pulmonary microvascular permeability seem to contribute to the progressive deterioration of oxygenation shown in the present study.
Pathological alterations in systemic microvasculature remote from the
lung have been described in various types of acute lung injury (8, 31,
49). There is increasing evidence indicating that systemic
microvascular derangements with acute lung injury are mediated by
activated neutrophils (18, 37, 43). St. John et al. (49) reported that
increased intestinal microvascular permeability after acid aspiration
can be prevented by inhibiting leukocyte adherence. In the present
study, it is quite conceivable that sustained increases in
slymph and sPI
in the nontreatment group are, at least in part, caused by activation
of PMNs associated with smoke inhalation.
Although improved permeability change in the LAM1-3 group was manifested as less positive fluid balance during the first day, it did not result in an earlier establishment of hemodynamic stability. There was no significant difference in hemodynamic data between the nontreatment and LAM1-3 groups. Mileski et al. (30), using a 30% BSA third-degree burn model in rabbits, demonstrated that inhibition of leukocyte adherence reversed the hypotensive response, whereas cardiac output was maintained during the experimental period. However, interpretation of their findings relevant to the clinical settings is difficult, as decreased mean arterial pressure is not a typical hemodynamic response to thermal injury in humans (53). It is well documented that depressed cardiac myocontractility contributes to hemodynamic alterations after severe thermal injury (21, 50). Horton and White (22) reported that leukocyte depletion did not ablate burn-induced cardiac depression, whereas an XO inhibitor (allopurinol) or inactivation (tungsten-enriched diet) provided a measure of cardioprotection. Neutrophil-independent cardiac depression might lead to the discouraging effects of LAM1-3 on hemodynamics in the present study.
In summary, this combined-injury model satisfactorily reproduced the hemodynamic alterations often seen in severely burned patients. A distinct difference in pathogenesis was noted between thermal injury and smoke inhalation. Both neutrophil-dependent and -independent mechanisms seem to be involved in this combined-injury model.
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ACKNOWLEDGEMENTS |
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This work was supported by National Institute for General Medical Sciences Grant GM33324 and Grants 8570 and 8450 from the Shriners of North America. D. L. Traber is Charles Robert Allen Professor of Anesthesiology.
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FOOTNOTES |
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The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.
Address for reprint requests and other correspondence: D. L. Traber, Investigational Intensive Care Unit, The Univ. of Texas Medical Branch, 610 Texas Ave., Galveston, TX 77555-0833.
Received 2 March 1998; accepted in final form 18 November 1998.
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REFERENCES |
|---|
|
TOP
ABSTRACT
INTRODUCTION
MATERIALS AND METHODS
RESULTS
DISCUSSION
REFERENCES
|
|---|
1.
Ahn, S. Y.,
K. Sugi,
P. Talke,
J. L. Theissen,
H. A. Linares,
L. D. Traber,
D. N. Herndon,
and
D. L. Traber.
Effects of allopurinol on smoke inhalation in the ovine model.
J. Appl. Physiol.
68:
228-234,
1990
2.
Albelda, S. M.,
C. W. Smith,
and
P. A. Ward.
Adhesion molecules and inflammatory injury.
FASEB J.
8:
504-512,
1994[Abstract].
3.
Alexander, F.,
M. Mathieson,
K. H. Teoh,
W. V. Huval,
S. Lelcuk,
C. R. Valeri,
and
H. B. Hechtman.
Arachidonic acid metabolites mediate early burn edema.
J. Trauma
24:
709-712,
1984[Medline].
4.
Anggard, E.,
and
C. E. Jonsson.
Efflux of prostaglandins in lymph from scalded tissue.
Acta Physiol. Scand.
81:
440-447,
1971[Medline].
5.
Basadre, J. O.,
K. Sugi,
D. L. Traber,
L. D. Traber,
G. D. Niehaus,
and
D. N. Herndon.
The effect of leukocyte depletion on smoke inhalation injury in sheep.
Surgery
104:
208-215,
1988[Medline].
6.
Baxter, C. R.,
and
T. Shires.
Physiological response to crystalloid resuscitation of severe burns.
Ann. NY Acad. Sci.
150:
874-894,
1968[Medline].
7.
Brazeal, B. A.,
D. Honeycutt,
L. D. Traber,
J. G. Toole,
D. N. Herndon,
and
D. L. Traber.
Pentafraction for superior resuscitation of the ovine thermal burn.
Crit. Care Med.
23:
332-339,
1995[Medline].
8.
Coalson, J. J.,
L. T. Archer,
B. A. Benjamin,
B. K. Beller-Todd,
and
L. B. Hinshaw.
A morphologic study of live Escherichia coli organism shock in baboons.
Exp. Mol. Pathol.
31:
10-22,
1979[Medline].
9.
Demling, R.,
C. LaLonde,
Y. K. Youn,
and
L. Picard.
Effect of graded increases in smoke inhalation injury on the early systemic response to a body burn.
Crit. Care Med.
23:
171-178,
1995[Medline].
10.
Demling, R. H.,
M. Smith,
R. Gunther,
T. Wandzilak,
and
N. C. Pederson.
Use of a chronic prefemoral lymphatic fistula for monitoring systemic capillary integrity in unanesthetized sheep.
J. Surg. Res.
31:
136-144,
1981[Medline].
11.
Dore, M.,
R. J. Korthuis,
D. N. Granger,
M. L. Entman,
and
C. W. Smith.
P-selectin mediates spontaneous leukocyte rolling in vivo.
Blood
82:
1308-1316,
1993
12.
Dubois, E. F.
The estimation of the surface area of the body.
In: Basal Metabolism in Health and Disease, edited by E. F. DuBois. Philadelphia, PA: Lea & Febiger, 1936, p. 125-144.
13.
Fakhry, S. M.,
J. Alexander,
D. Smith,
A. A. Meyer,
and
H. D. Peterson.
Regional and institutional variation in burn care.
J. Burn Care Rehabil.
16:
86-90,
1995[Medline].
14.
Ferguson, J. L.,
G. F. Merrill,
H. I. Miller,
and
J. J. Spitzer.
Regional blood flow redistribution during early burn shock in the guinea pig.
Circ. Shock
4:
317-326,
1977[Medline].
15.
Ferrara, J. J.,
E. W. Franklin,
E. U. Choe,
H. L. Lippton,
A. L. Hyman,
and
L. M. Flint.
Effects of methysergide administration on edema formation at the site of scald.
J. Appl. Physiol.
78:
191-197,
1995
16.
Ferrara, J. J.,
E. W. Franklin,
E. U. Choe,
P. A. Taheri,
C. L. Westervelt,
H. L. Lippton,
A. L. Hyman,
and
L. M. Flint.
Serotonin receptors regulate canine regional vasodilator responses to burn.
Crit. Care Med.
23:
1112-1116,
1995[Medline].
17.
Friedl, H. P.,
G. O. Till,
O. Trentz,
and
P. A. Ward.
Roles of histamine, complement and xanthine oxidase in thermal injury of skin.
Am. J. Pathol.
135:
203-217,
1989[Abstract].
18.
Goldman, G.,
R. Welbourn,
J. M. Klausner,
L. Kobzik,
C. R. S. Valeri,
and
H. B. Hechtman.
Leukocytes mediate acid aspiration-induced multiorgan edema.
Surgery
114:
13-20,
1993[Medline].
19.
Hansbrough, J. F.,
T. Wikstrom,
M. Braide,
M. Tenenhaus,
O. H. Rennekampff,
R. Zapata-Sirvent,
and
L. M. Bjursten.
Effects of E-selectin and P-selectin blockade on neutrophil sequestration in tissues and neutrophil oxidative burst in burned rats.
Crit. Care Med.
24:
1366-1372,
1996[Medline].
20.
Herndon, D. N.,
P. B. Thompson,
H. A. Linares,
and
D. L. Traber.
Postgraduate course: respiratory injury. Part I: incidence, mortality, pathogenesis and treatment of pulmonary injury.
J. Burn Care Rehabil.
7:
184-191,
1986[Medline].
21.
Horton, J. W.,
C. R. Baxter,
and
D. J. White.
Differences in cardiac responses to resuscitation from burn shock.
Surg. Gynecol. Obstet.
168:
201-213,
1989[Medline].
22.
Horton, J. W.,
and
D. J. White.
Role of xanthine oxidase and leukocytes in postburn cardiac dysfunction.
J. Am. Coll. Surg.
181:
129-137,
1995[Medline].
23.
Hudson, L.
Delayed hypoxemia in smoke inhalation (Abstract).
Clin. Res.
19:
191,
1971.
24.
Keeney, S. E.,
M. J. Mathews,
A. K. Haque,
H. E. Rudloff,
and
F. C. Schmalstieg.
Oxygen-induced lung injury in the guinea pig proceeds through CD18-independent mechanisms.
Am. J. Respir. Crit. Care Med.
149:
311-319,
1994[Abstract].
25.
Kimura, R.,
R. Mlcak,
J. Richardson,
M. Desai,
D. Herndon,
L. D. Traber,
and
D. L. Traber.
Treatment of smoke-induced pulmonary injury with nebulized dimethylsulfoxide.
Circ. Shock
25:
333-341,
1988[Medline].
26.
Kimura, R.,
L. D. Traber,
D. N. Herndon,
H. A. Linares,
H. J. Lübbesmeyer,
and
D. L. Traber.
Increasing duration of smoke exposure induces more severe lung injury in sheep.
J. Appl. Physiol.
64:
1107-1113,
1988
27.
Knol, E. F.,
F. Tackey,
T. F. Tedder,
D. A. Klunk,
C. A. Bickel,
and
B. S. Bochner.
Comparison of human eosinophil and neutrophil adhesion to endothelial cells under nonstatic conditions. Role of L-selectin.
J. Immunol.
153:
2161-2167,
1994[Abstract].
28.
Lund, T.,
H. Wiig,
and
R. K. Reed.
Acute postburn edema: role of strongly negative interstitial fluid pressure.
Am. J. Physiol.
255 (Heart Circ. Physiol. 24):
H1069-H1074,
1988
29.
Mileski, W.,
D. Borgstrom,
E. Lightfoot,
R. Rothlein,
R. Faanes,
and
P. Lipsky.
Inhibition of leukocyte-endothelial adherence following thermal injury.
J. Surg. Res.
52:
334-339,
1992[Medline].
30.
Mileski, W.,
B. Gates,
A. Sigman,
P. Sikes,
L. Atiles,
E. Lightfoot,
P. Lipsky,
and
C. Baxter.
Inhibition of leukocyte adherence in a rabbit model of major thermal injury.
J. Burn Care Rehabil.
14:
610-616,
1993[Medline].
31.
Mizer, L. A.,
S. E. Weisbrode,
and
P. M. Dorinsky.
Neutrophil accumulation and structural changes in nonpulmonary organs after acute lung injury induced by phorbol myristate acetate.
Am. Rev. Respir. Dis.
139:
1017-1026,
1989[Medline].
32.
Moncrief, J. A.
Effect of various fluid regimens and pharmacologic agents on the circulatory hemodynamics of the immediate postburn period.
Ann. Surg.
164:
723-752,
1966[Medline].
33.
Mulligan, M. S.,
K. J. Johnson,
R. Todd III,
T. B. Issekutz,
M. Miyasaka,
T. Tamatani,
C. W. Smith,
D. C. Anderson,
and
P. A. Ward.
Requirements for leukocyte adhesion molecules in nephrotoxic nephritis.
J. Clin. Invest.
91:
577-587,
1993.
34.
Mulligan, M. S.,
G. O. Till,
C. W. Smith,
D. C. Anderson,
M. Miyasaka,
T. Tamatani,
T. B. Issekutz,
and
P. A. Ward.
Role of leukocyte adhesion molecules in lung and dermal vascular injury after thermal trauma of skin.
Am. J. Pathol.
144:
1008-1015,
1994[Abstract].
35.
Navar, P. D.,
J. R. Saffle,
and
G. D. Warden.
Effect of inhalation injury on fluid resuscitation requirements after thermal injury.
Am. J. Surg.
150:
716-720,
1985[Medline].
36.
Nguyen, T. T.,
C. S. Cox, Jr.,
D. N. Herndon,
N. A. Biondo,
L. D. Traber,
P. E. Bush,
and
D. L. Traber.
Effects of manganese superoxide dismutase on lung fluid balance after smoke inhalation.
J. Appl. Physiol.
78:
2161-2168,
1995
37.
Nishizawa, H.,
H. Yamada,
H. Miyazaki,
M. Ohara,
K. Kaneko,
T. Yamakawa,
and
I. Kudoh.
Soluble complement receptor type 1 inhibited the systemic organ injury caused by acid instillation into a lung.
Anesthesiology
85:
1120-1128,
1996[Medline].
38.
Nwariaku, F.,
P. J. Sikes,
E. Lightfoot, Jr.,
and
W. J. Mileski.
Inhibition of selectin- and integrin-mediated inflammatory response after burn injury.
J. Surg. Res.
63:
355-358,
1996[Medline].
39.
Pitt, R. M.,
J. C. Parker,
G. J. Jurkovich,
A. E. Taylor,
and
P. W. Curreri.
Analysis of altered capillary pressure and permeability after thermal injury.
J. Surg. Res.
42:
693-702,
1987[Medline].
40.
Putman, C. E., J. Loke, R. A. Matthay, and
C. E. Ravin. Radiographic manifestations of acute smoke
inhalation. Am. J. Respir.
Res.: 865-870, 1977.
41.
Rocha, E.,
M. Silva,
and
A. Antonio.
Release of bradykinin and the mechanism of production of thermic edema (45°C) in the rat paw.
Med. Exp.
3:
371-382,
1960.
42.
Rosengren, S.,
A. M. Olofsson,
U. H. Von Andrian,
and
E. Lundgren-Akerlund and Arforske.
Leukotriene B4-induced neutrophil-mediated endothelial leakage in vitro and in vivo.
J. Appl. Physiol.
71:
1322-1330,
1991
43.
Rossi, F.
The O2-forming NADPH oxidase of the phagocytes: nature, mechanisms of activation and function.
Biochim. Biophys. Acta
853:
65-89,
1986[Medline].
44.
Sakurai, H.,
R. Johnigan,
Y. Kikuchi,
M. Harada,
L. D. Traber,
and
D. L. Traber.
Effect of reduced bronchial circulation on lung fluid flux after smoke inhalation in sheep.
J. Appl. Physiol.
84:
980-985,
1998
45.
Scheulen, J. J.,
and
A. M. Munster.
The Parkland formula in patients with burns and inhalation injury.
J. Trauma
22:
869-871,
1982[Medline].
46.
Shimazu, T.,
T. Yukioka,
H. Ikeuchi,
A. D. Mason, Jr.,
P. D. Wagner,
and
B. A. Pruitt, Jr.
Ventilation-perfusion alterations after smoke inhalation injury in an ovine model.
J. Appl. Physiol.
81:
2250-2259,
1996
47.
Spertini, O.,
G. S. Kansas,
K. A. Reimann,
C. R. Mackay,
and
T. F. Tedder.
Function and evolutionary conservation of distinct epitopes on the leukocyte adhesion molecule-1 (TQ-1, Leu-8) that regulate leukocyte migration.
J. Immunol.
147:
942-949,
1991[Abstract].
48.
Staub, N. C.,
R. D. Bland,
K. L. Brigham,
R. Demling,
A. J. Erdmann,
and
W. C. Woolverton.
Preparation of chronic lung lymph fistulas in sheep.
J. Surg. Res.
19:
315-320,
1975[Medline].
49.
St. John, R. C.,
L. A. Mizer,
G. C. Kindt,
S. E. Weisbrode,
S. A. Moore,
and
P. M. Dorinsky.
Acid aspiration-induced acute lung injury causes leukocyte-dependent systemic organ injury.
J. Appl. Physiol.
74:
1994-2003,
1993
50.
Suzuki, K.,
M. Nishina,
R. Ogino,
and
A. Kohama.
Left ventricular contractility and diastolic properties in anesthetized dogs after severe burns.
Am. J. Physiol.
260 (Heart Circ. Physiol. 29):
H1433-H1442,
1991
51.
Till, G. O.,
L. S. Guilds,
M. Mahrougui,
H. P. Friedl,
O. Trentz,
and
P. A. Ward.
Role of xanthine oxidase in thermal injury of skin.
Am. J. Pathol.
135:
195-202,
1989[Abstract].
52.
Traber, D. L.,
D. N. Herndon,
M. D. Stein,
L. D. Traber,
J. T. Flynn,
and
G. D. Niehaus.
The pulmonary lesion of smoke inhalation in an ovine model.
Circ. Shock
18:
311-323,
1986[Medline].
53.
Wolfe, R. R.
Review: acute versus chronic response to burn injury.
Circ. Shock
8:
105-115,
1981[Medline].
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Significantly different from control group,
P < 0.05. # Significantly different
from nontreatment group, P < 0.05.
