Role of anti-L-selectin antibody in burn and smoke inhalation injury in sheep

2002 ◽  
Vol 283 (5) ◽  
pp. L1043-L1050 ◽  
Author(s):  
Jiro Katahira ◽  
Kazunori Murakami ◽  
Frank C. Schmalstieg ◽  
Robert Cox ◽  
Hal Hawkins ◽  
...  
Keyword(s):  
Leukocyte Adhesion ◽  
Experimental Period ◽  
Inhalation Injury ◽  
Lymph Flow ◽  
Smoke Inhalation ◽  
Control Group ◽  
Fluid Flux ◽  
Smoke Inhalation Injury ◽  
Lung Lymph ◽  
Lung Lymph Flow

We hypothesized that the antibody neutralization of L-selectin would decrease the pulmonary abnormalities characteristic of burn and smoke inhalation injury. Three groups of sheep ( n = 18) were prepared and randomized: the LAM-(1–3) group ( n = 6) was injected intravenously with 1 mg/kg of leukocyte adhesion molecule (LAM)-(1-3) (mouse monoclonal antibody against L-selectin) 1 h after the injury, the control group ( n = 6) was not injured or treated, and the nontreatment group ( n = 6) was injured but not treated. All animals were mechanically ventilated during the 48-h experimental period. The ratio of arterial Po 2 to inspired O2 fraction decreased in the LAM-(1–3) and nontreatment groups. Lung lymph flow and pulmonary microvascular permeability were elevated after injury. This elevation was significantly reduced when LAM-(1–3) was administered 1 h after injury. Nitrate/nitrite (NO x ) amounts in plasma and lung lymph increased significantly after the combined injury. These changes were attenuated by posttreatment with LAM-(1–3). These results suggest that the changes in pulmonary transvascular fluid flux result from injury of lung endothelium by polymorphonuclear leukocytes. In conclusion, posttreatment with the antibody for L-selectin improved lung lymph flow and permeability index. L-selectin appears to be principally involved in the increased pulmonary transvascular fluid flux observed with burn/smoke insult. L-selectin may be a useful target in the treatment of acute lung injury after burn and smoke inhalation.

Role of sulfidopeptide leukotrienes in synthetic smoke inhalation injury in sheep

1990 ◽  
Vol 68 (5) ◽  
pp. 1962-1969 ◽  
Author(s):  
D. A. Quinn ◽  
D. Robinson ◽  
W. Jung ◽  
C. A. Hales
Keyword(s):  
Systemic Vascular Resistance ◽  
Vascular Resistance ◽  
Weight Ratio ◽  
Inhalation Injury ◽  
Lymph Flow ◽  
Smoke Inhalation ◽  
Lung Water ◽  
Smoke Inhalation Injury ◽  
Lung Lymph ◽  
Lung Lymph Flow

Acute lung injury with smoke inhalation results in significant morbidity and mortality. Previously we have shown that synthetic smoke composed of carbon and acrolein, a common component of smoke, causes delayed-onset noncardiogenic pulmonary edema. To study the possible role of the vasoactive and edemagenic sulfidopeptide leukotrienes (SPLT) in smoke inhalation injury, we measured pulmonary hemodynamics, lung lymph flow, and SPLT and leukotriene (LT) B4 in lung lymph before and after 10 min of synthetic acrolein smoke exposure. After smoke exposure there was a significant rise in pulmonary vascular resistance caused by a rise in pulmonary arterial pressure, a fall in cardiac output, and no change in pulmonary capillary wedge pressure. This was accompanied by an increase in total systemic vascular resistance (P less than 0.05), lung lymph flow (P less than 0.05), and extravascular lung water-to-lung dry weight ratio (P less than 0.05). Both SPLT and LTB4 clearance rose significantly (P less than 0.05), but there was a 10-fold increase in SPLT over LTB4 clearance. In sheep pretreated with FPL55712, a SPLT antagonist, the early rise in pulmonary vascular resistance was attenuated, and the rise in systemic vascular resistance was blocked. This was associated with an attenuated and delayed fall in cardiac output. FPL55712 had no effect on lung lymph flow or extravascular lung water-to-dry weight ratio. SPLT, and especially LTD4, may have a role in increased pulmonary and systemic vascular resistance after smoke inhalation injury but does not appear to affect vascular permeability.

EFFECTS OF MANGANESE SUPEROXIDE DISMUTASE NEBULIZATION ON LUNG LYMPH FLOW AFTER OVINE SMOKE INHALATION INJURY

2004 ◽  
Vol 32 (Supplement) ◽  
pp. A24
Author(s):  
Marc O Maybauer ◽  
Dirk M Maybauer ◽  
Yuji Kikuchi ◽  
Martin Westphal ◽  
Lillian D Traber ◽  
...  
Keyword(s):  
Superoxide Dismutase ◽  
Manganese Superoxide Dismutase ◽  
Inhalation Injury ◽  
Lymph Flow ◽  
Smoke Inhalation ◽  
Smoke Inhalation Injury ◽  
Manganese Superoxide ◽  
Lung Lymph ◽  
Lung Lymph Flow

Selective Thromboxane A2Synthase Inhibition by OKY-046 Prevents Cardiopulmonary Dysfunction after Ovine Smoke Inhalation Injury

2005 ◽  
Vol 102 (5) ◽  
pp. 954-961 ◽  
Author(s):  
Martin Westphal ◽  
Shinji Noshima ◽  
Tsukasa Isago ◽  
Kentarou Fujioka ◽  
Marc O. Maybauer ◽  
...  
Keyword(s):  
Cardiac Output ◽  
Vascular Resistance ◽  
Systolic Pressure ◽  
Thromboxane A2 ◽  
Inhalation Injury ◽  
Thromboxane B2 ◽  
Smoke Inhalation ◽  
Control Group ◽  
Smoke Inhalation Injury ◽  
Lung Lymph

Background Because thromboxane A2 is implicated in the pathophysiology of acute lung injury, the aim of this study was to evaluate the effects of selective thromboxane A2 synthase inhibition on cardiopulmonary function in the experimental setting of severe smoke inhalation injury. Methods Sixteen adult sheep were operatively instrumented for chronic study. The injured intervention group was treated with the selective thromboxane A2 synthase inhibitor OKY-046, whereas the injured control group received only the vehicle (n = 8 each). Results The progressive increase in thromboxane B2 lung lymph concentrations in control animals was associated with increased transvascular fluid flux, augmented resistances in the pulmonary and systemic circulation, and a reciprocal decrease in cardiac output. In addition, end-systolic pressure-diameter relation and maximum +dp/dt were markedly depressed as compared with baseline (24 h: 14.3 +/- 0.9 vs. 8.9 +/- 0.5 mmHg/mm and 2,120 +/- 50 vs. 1,915 +/- 40 mmHg/s, respectively; each P < 0.05). Infusion of OKY-046 significantly inhibited pulmonary thromboxane B2 delivery, attenuated the early increase in pulmonary vascular resistance, and blocked the increase in systemic vascular resistance. In addition, OKY-046 blunted and delayed the decrease in cardiac output and maintained end-systolic pressure-diameter relation, +dp/dt, and lung lymph flow at baseline values. Conclusions These findings suggest that selective thromboxane A2 synthase inhibition may represent a goal-directed therapeutic approach to alleviate cardiovascular and pulmonary dysfunction in the setting of smoke inhalation injury.

Increasing duration of smoke exposure induces more severe lung injury in sheep

1988 ◽  
Vol 64 (3) ◽  
pp. 1107-1113 ◽  
Author(s):  
R. Kimura ◽  
L. D. Traber ◽  
D. N. Herndon ◽  
H. A. Linares ◽  
H. J. Lubbesmeyer ◽  
...  
Keyword(s):  
Lung Injury ◽  
Inhalation Injury ◽  
Lymph Flow ◽  
Smoke Inhalation ◽  
Lung Water ◽  
Arterial Blood ◽  
Chronic Study ◽  
Lung Lymph ◽  
Severe Lung ◽  
Lung Lymph Flow

Eighteen sheep previously prepared for chronic study were divided into three groups of six animals each. These were given graded inhalation injury utilizing smoke obtained from burning cotton-toweling material. Smoke was insufflated into animals with a modified bee smoker at temperatures less than 40 degrees C. Group H, which received 64 breaths of smoke, showed the most pronounced changes in pulmonary function. The changes consisted mainly of a profound increase in lung lymph flow following a reduced P/F ratio (PO2 in arterial blood/inspired O2 fraction) and an elevation in both thermal and gravimetrically measured extravascular lung water. Similar changes were seen in group M (48 breaths of smoke) and group L (32 breaths of smoke). However, the injury was graded based on the changes in gravimetrically measured lung water and lung lymph flow. These were highest in group H and lowest in group L. These studies confirm our ability to accurately quantitate the injury induced by smoke inhalation. In addition, it demonstrates that lung injury associated with the inhalation of smoke can be graded depending on the duration of exposure.

Role of L-selectin in physiological manifestations after burn and smoke inhalation injury in sheep

1999 ◽  
Vol 86 (4) ◽  
pp. 1151-1159 ◽  
Author(s):  
Hiroyuki Sakurai ◽  
Frank C. Schmalstieg ◽  
Lillian D. Traber ◽  
Hal K. Hawkins ◽  
Daniel L. Traber
Keyword(s):  
Pressure Ratio ◽  
Inhalation Injury ◽  
Lymph Flow ◽  
Smoke Inhalation ◽  
Burned Area ◽  
Control Group ◽  
Initial Increase ◽  
Smoke Inhalation Injury ◽  
Delayed Onset ◽  
Combined Injury

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 (sQ˙lymph) from the burned area and a delayed-onset increase in lung lymph flow. The initial increase in sQ˙lymphwas 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 sQ˙lymphand 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.

Pulmonary transvascular fluid flux and cardiovascular function in sheep with chronic sepsis

1993 ◽  
Vol 75 (6) ◽  
pp. 2521-2528 ◽  
Author(s):  
H. Nakazawa ◽  
H. Noda ◽  
S. Noshima ◽  
J. T. Flynn ◽  
L. D. Traber ◽  
...  
Keyword(s):  
Mean Arterial Pressure ◽  
Reflection Coefficient ◽  
Resistance Index ◽  
Ringer Solution ◽  
Lymph Flow ◽  
Control Group ◽  
Systemic Vascular Resistance Index ◽  
Fluid Flux ◽  
Lung Lymph ◽  
Lung Lymph Flow

We studied the mechanisms responsible for the changes in lung lymph flow (QL) in chronic sepsis induced by the continuous infusion of endotoxin [lipopolysaccharide (LPS), 10 ng.kg-1.min-1]. Sheep (n = 11) were studied in the unanesthetized state 7 days after preparation, and cardiopulmonary variables were measured. In the control group (n = 5) given lactated Ringer solution, no significant changes were observed in any measured variables. In the LPS group (n = 6), QL increased from 11.7 +/- 3.8 to 54.0 +/- 15.0 (SE) ml/h 24 h after LPS infusion had begun. This elevation in QL was associated with little or no change (P > 0.05) in reflection coefficient (0.80 +/- 0.03 to 0.87 +/- 0.05) or pulmonary microvascular pressure (14.3 +/- 0.4 to 16.7 +/- 1.2 mmHg). The filtration coefficient, however, was significantly elevated (0.018 +/- 0.006 to 0.083 +/- 0.024 ml.min-1.mmHg-1). In association with changes in QL that occur as a result of LPS administration, there was a significant increase in cardiac index (6.1 +/- 0.5 to 10.2 +/- 0.3 l.min-1.m-2) and a reduction in mean arterial pressure (90.2 +/- 4.4 to 73.7 +/- 7.3 mmHg) and systemic vascular resistance index (1,229 +/- 134 to 583 +/- 62 dyn.s.cm-5.m2), findings similar to those noted in septic humans.

scholarly journals Effect of reduced bronchial circulation on lung fluid flux after smoke inhalation in sheep

1998 ◽  
Vol 84 (3) ◽  
pp. 980-986 ◽  
Author(s):  
Hiroyuki Sakurai ◽  
Richard Johnigan ◽  
Yuji Kikuchi ◽  
Mikihiko Harada ◽  
Lillian D. Traber ◽  
...  
Keyword(s):  
Blood Flow ◽  
Sham Group ◽  
Bronchial Artery ◽  
Lymph Flow ◽  
Smoke Inhalation ◽  
Fluid Flux ◽  
Lung Fluid ◽  
Injection Group ◽  
Lung Lymph ◽  
Lung Lymph Flow

We determined the effect of reduced bronchial blood flow on lung fluid flux through changes in lung lymph flow, lung wet weight-to-dry weight (wet/dry) ratios, and pulmonary microvascular reflection coefficient (ς). In the first of two surgical procedures, Merino ewes ( n = 21) were surgically prepared for chronic study. Five to seven days later, in a second operation, the bronchial artery of the injection group ( n = 7) was ligated, and 4 ml of 70% ethanol were injected into the bronchial artery to cause sclerosis of the airway circulation. In the ligation group ( n = 7), only the bronchial artery was ligated. In the sham group ( n = 7), the bronchial artery was surgically exposed but left intact without ligation or ethanol injection. One day after these operations the animals received a tracheotomy and 48 breaths of cotton smoke. The value of ς was determined at two points: 24 h before the second surgical procedure and 24 h after smoke inhalation. Lung lymph flow, blood-gas parameters, and hemodynamic data were measured every 4 h after injury. At the end of investigation, samples of lung were taken for determination of blood-free wet/dry ratio. In the sham group, inhalation injury induced a gradual increase in pulmonary vascular resistance and lung lymph flow, which was associated with deterioration of oxygenation. Reduction of the bronchial blood flow attenuated these pathophysiological changes, and the degree of this attenuation was greater in the injection group than in the ligation group. The value of ς was significantly higher after smoke inhalation in the injection group compared with the sham group (0.77 ± 0.04 vs. 0.61 ± 0.03, means ± SE) at 24 h. The mean wet/dry ratio value of the injection group animals was 30% less than that of the sham group. Our data show that the bronchial circulation contributes to edema formation in the lung occurring after acute lung injury with smoke inhalation.

alpha-Trinositol decreases lung edema formation after smoke inhalation in an ovine model

1994 ◽  
Vol 76 (1) ◽  
pp. 278-282 ◽  
Author(s):  
H. Nakazawa ◽  
T. O. Gustafsson ◽  
L. D. Traber ◽  
D. N. Herndon ◽  
D. L. Traber
Keyword(s):  
Thermal Injury ◽  
Sham Group ◽  
Inhalation Injury ◽  
Smoke Inhalation ◽  
Lung Edema ◽  
Ovine Model ◽  
Edema Formation ◽  
Surgical Preparation ◽  
Lung Lymph ◽  
Lung Lymph Flow

Inhalation injury is a dominant cause of mortality in thermally injured individuals. After acute lung injury induced by smoke inhalation, lung lymph flow (QL) increased and pulmonary microvascular reflection coefficient to protein (sigma) decreased. alpha-Trinositol (PP56, 1D-myo-inositol 1,2,6-trisphosphate) can decrease edema formation after thermal injury. We therefore tested the hypothesis that alpha-trinositol could decrease the pulmonary edema noted with inhalation injury. Seven days after surgical preparation, sheep were insufflated with smoke from burning cotton towels. The alpha-trinositol group (n = 8) were treated with alpha-trinositol (2 mg/kg + 3.5 mg.kg-1 x h-1). The sham group (n = 7) received an equal volume of 0.9% NaCl. The sham group showed a large increase in QL (9.3 +/- 1.7 to 54.1 +/- 8.8 ml/h) and a decrease in sigma (0.79 +/- 0.03 to 0.48 +/- 0.03) 24 h after smoke inhalation. alpha-Trinositol attenuated the increase in QL (8.1 +/- 1.2 to 25.6 +/- 6.9 ml/h) and the decrease in sigma (0.76 +/- 0.03 to 0.60 +/- 0.03) noted with smoke inhalation. alpha-Trinositol thus decreased the changes in pulmonary microvascular permeability and transvascular fluid flux noted with inhalation injury.

scholarly journals Dynamic Tracking Human Mesenchymal Stem Cells Tropism following Smoke Inhalation Injury in NOD/SCID Mice

2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
MeiJuan Song ◽  
Qi Lv ◽  
XiuWei Zhang ◽  
Juan Cao ◽  
ShuLi Sun ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Inhalation Injury ◽  
Scid Mice ◽  
Alveolar Epithelial Cells ◽  
Smoke Inhalation ◽  
Control Group ◽  
Smoke Inhalation Injury

Multiple preclinical evidences have supported the potential value of mesenchymal stem cells (MSCs) for treatment of acute lung injury (ALI). However, few studies focus on the dynamic tropism of MSCs in animals with acute lung injury. In this study, we track systemically transplanted human bone marrow-derived mesenchymal stem cells (hBMSCs) in NOD/SCID mice with smoke inhalation injury (SII) through bioluminescence imaging (BLI). The results showed that hBMSCs systemically delivered into healthy NOD/SCID mouse initially reside in the lungs and then partially translocate to the abdomen after 24 h. Compared with the uninjured control group treated with hBMSCs, higher numbers of hBMSCs were found in the lungs of the SII NOD/SCID mice. In both the uninjured and SII mice, the BLI signals in the lungs steadily decreased over time and disappeared by 5 days after treatment. hBMSCs significantly attenuated lung injury, elevated the levels of KGF, decreased the levels of TNF-αin BALF, and inhibited inflammatory cell infiltration in the mice with SII. In conclusion, our findings demonstrated that more systemically infused hBMSCs localized to the lungs in mice with SII. hBMSC xenografts repaired smoke inhalation-induced lung injury in mice. This repair was maybe due to the effect of anti-inflammatory and secreting KGF of hMSCs but not associated with the differentiation of the hBMSCs into alveolar epithelial cells.

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