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David N. Herndon - One of the best experts on this subject based on the ideXlab platform.
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adipose derived stem cells attenuate pulmonary microvascular hyperpermeability after smoke inhalation
PLOS ONE, 2017Co-Authors: Koji Ihara, Satoshi Fukuda, Baigalmaa Enkhtaivan, Raul Trujillo, Dannelys Perezbello, Christina Nelson, Anita Randolph, Suzan Alharbi, Hira Hanif, David N. HerndonAbstract:Background Pulmonary edema is a hallmark of acute respiratory distress syndrome (ARDS). Smoke inhalation causes ARDS, thus significantly increasing the mortality of burn patients. Adipose-derived stem cells (ASCs) exert potent anti-inflammatory properties. The goal of the present study was to test the safety and ecfficacy of ASCs, in a well-characterized clinically relevant ovine model of ARDS. Methods Female sheep were surgically prepared. ARDS was induced by cooled cotton smoke inhalation. Following injury, sheep were ventilated, resuscitated with lactated Ringer’s solution, and cardiopulmonary hemodynamics were monitored for 48 hours in a conscious state. Pulmonary microvascular hyper-permeability was assessed by measuring Lung Lymph flow, extravascular Lung water content, protein content in plasma and Lung Lymph fluid. Sheep were randomly allocated to two groups: 1) ASCs: infused with 200 million of ASCs in 200mL of PlasmaLyteA starting 1 hours post-injury, n = 5; 2) control, treated with 200mL of PlasmaLyteA in a similar pattern, n = 5. Results Lung Lymph flow increased 9-fold in control sheep as compared to baseline. Protein in the plasma was significantly decreased, while it was increased in the Lung Lymph. The treatment with ASCs significantly attenuated these changes. Treatment with ASCs almost led to the reversal of increased pulmonary vascular permeability and Lung water content. Pulmonary gas exchange was significantly improved by ASCs. Infusion of the ASCs did not negatively affect pulmonary artery pressure and other hemodynamic variables. Conclusions ASCs infusion was well tolerated. The results suggest that intravenous ASCs modulate pulmonary microvascular hyper-permeability and prevent the onset of ARDS in our experimental model.
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abstract 19670 adipose derived mesenchymal stem cells attenuate pulmonary microvascular hyperpermeability after smoke inhalation
Circulation, 2015Co-Authors: Koji Ihara, David N. Herndon, Satoshi Fukuda, Baigalmaa Enkhtaivan, Raul Trujillo, Ernesto Lopez, Hal K Hawkins, Donald S Prough, Perenlei EnkhbaatarAbstract:Pulmonary edema is a hallmark of acute respiratory distress syndrome (ARDS). Smoke inhalation causes ARDS, significantly increasing the mortality of burn patients. Mesenchymal stem cells (MSCs) exert potent anti-inflammatory properties. The goal of the present study was to test the safety and efficacy of MSCs in a well-characterized clinically relevant ovine model of ARDS. Methods: Female sheep (30-40 kg) were surgically prepared 5-7 days prior the study. ARDS was induced by cooled cotton smoke inhalation. Following the injury, sheep were ventilated, resuscitated with lactated Ringer’s solution and cardiopulmonary hemodynamics was monitored for 48 h in a conscious state. Pulmonary microvascular hyper-permeability was assessed by measuring Lung Lymph flow, extravascular Lung water content, protein in plasma and Lung Lymph. Sheep were randomly allocated to two groups: 1) MSCs: infused with 5 million/kg of intravenous MSCs over 30min starting 1 h post-injury, n=5; 2) control, treated with a vehicle in a similar pattern (200ml of PlasmaLyte A), n=5. Results: Lung Lymph flow, an index of pulmonary transvascular fluid flux was ~7-fold increased in control sheep compared to baseline. This was associated with a significant protein decrease in plasma and its increase in Lung Lymph. The treatment with MSCs significantly attenuated these changes (Table). Moreover, the treatment with MSCs almost reversed increased pulmonary vascular permeability index {(Lung Lymph proteinхLung Lymph flow)/plasma protein} and reduced Lung water content (Lung wet-to-dry weight ratio). Pulmonary gas exchange was significantly improved by MSCs (PaO2/FiO2 was 406±101 in MSCs and 262±127 in control at 24 hrs, p Conclusions: MSCs infusion was well tolerated. The results suggest that intravenous MSCs modulate pulmonary microvascular hyper-permeability and prevent onset of ARDS.
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pulmonary microvascular hyperpermeability and expression of vascular endothelial growth factor in smoke inhalation and pneumonia induced acute Lung injury
Burns, 2012Co-Authors: David N. Herndon, Matthias Lange, Yoshimitsu Nakano, Atsumori Hamahata, Lillian D. Traber, Daniel L Traber, Rhykka L Connelly, Frank C Schmalstieg, Perenlei EnkhbaatarAbstract:Abstract Introduction Acute Lung injury (ALI) and sepsis are major contributors to the morbidity and mortality of critically ill patients. The current study was designed further evaluate the mechanism of pulmonary vascular hyperpermeability in sheep with these injuries. Methods Sheep were randomized to a sham-injured control group ( n = 6) or ALI/sepsis group ( n = 7). The sheep in the ALI/sepsis group received inhalation injury followed by instillation of Pseudomonas aeruginosa into the Lungs. These groups were monitored for 24 h. Additional sheep ( n = 16) received the injury and Lung tissue was harvested at different time points to measure Lung wet/dry weight ratio, vascular endothelial growth factor (VEGF) mRNA and protein expression as well as 3-nitrotyrosine protein expression in Lung homogenates. Results The injury induced severe deterioration in pulmonary gas exchange, increases in Lung Lymph flow and protein content, and Lung water content ( P P Conclusions This study describes the time course of pulmonary microvascular hyperpermeability in a clinical relevant large animal model and may improve the experimental design of future studies.
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effects of a dual endothelin 1 receptor antagonist on airway obstruction and acute Lung injury in sheep following smoke inhalation and burn injury
Clinical Science, 2005Co-Authors: David N. Herndon, Robert A. Cox, L D Traber, Perenlei Enkhabaatar, Ann S Burke, Jiro Katahira, Katahiro Shimoda, Abhijit ChandraAbstract:Studies have suggested that ET-1 (endothelin-1) is associated with Lung injury, airway inflammation and increased vascular permeability. In the present study we have tested the hypothesis that treatment with a dual ET-1 receptor antagonist will decrease airway obstruction and improve pulmonary function in sheep with combined S+B (smoke inhalation and burn) injury. Twelve sheep received S+B injury using the following protocol: six sheep were treated with tezosentan, an ETA and ETB receptor antagonist, and six sheep received an equivalent volume of vehicle. Physiological and morphological variables were assessed during the 48 h study period and at the end of the study. There was no statistically significant difference in the PaO2/FiO2 (partial pressure of O2 in arterial blood/fraction of O2 in the inspired gas) ratio of the tezosentan-treated animals compared with controls; however, Lung Lymph flow was significantly higher (P<0.05) in the treated animals. PVRI (pulmonary vascular resistance index) was significantly reduced (P<0.05) in the tezosentan-treated animals. Assessment of NOx (nitric oxide metabolite) levels in plasma and Lymph showed significantly elevated (P<0.05) levels in the tezosentan-treated animals compared with levels in untreated sheep. The degree of bronchial obstruction was similar in both treated and control sheep; however, bronchiolar obstruction was reduced in sheep treated with tezosentan. Histopathologically, no difference in the degree of parenchymal injury was detected. In conclusion, administration of a dual ET-1 receptor antagonist prevented an increase in PVRI after injury and reduced the degree of bronchiolar obstruction in sheep with S+B; however, treated sheep showed higher levels of NOx and increased Lung Lymph flow. Tezosentan treatment was ineffective in protecting against acute Lung injury in this model.
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unilateral smoke inhalation in sheep effect on left Lung Lymph flow with right Lung injury
American Journal of Physiology-regulatory Integrative and Comparative Physiology, 1996Co-Authors: Yuji Kikuchi, David N. Herndon, L D Traber, Daniel L TraberAbstract:We previously reported that smoke inhalation to the right Lung will result in damage to the air-insufflated left Lung. In this study we confirm these findings and determine whether this injury is associated with an elevation in Lung Lymph flow and pulmonary microvascular permeability to protein as indexed by changes in reflection coefficient. Sheep (n = 12) were surgically prepared by placement of a Swan-Ganz catheter and pneumatic occluders on all pulmonary veins and the left pulmonary artery. The left Lung Lymphatic was selectively cannulated as shown previously (Y. Kikuchi, H. Nakazawa, and D. Traber. Am. J. Physiol. 269 (Regulatory Integrative Comp. Physiol. 38): R943-R947, 1995). All afferent Lymphatics from the right Lung were severed, and the right pulmonary ligament was sectioned. The caudal end of the Lymph node was sectioned to remove systemic Lymph contamination. The sheep were studied in the unanesthetized state 7 days later. To ensure that Lymph flow was exclusively from the left Lung (QLL), right pulmonary microvascular pressure was increased, a procedure that resulted in little or no change in QLL, as was previously shown. The sheep were then anesthetized, and a Carlens tube was positioned to allow separate ventilation of the right and left Lung. The right Lungs of five sheep and the left Lungs of two sheep were insufflated with cotton smoke. Insufflation of the left Lung with cotton smoke produced a fourfold increase in QLL that began 4 h after insult. Insufflation of the right Lung with smoke led to a doubling of QLL that began 12 h after insult. Changes in QLL were associated with increased microvascular permeability, as indexed by the reflection coefficient. Control sheep (air insufflated into both Lungs, n = 5) showed no change in QLL. Injury to the right Lung resulted in damage to the left air-insufflated Lung, suggesting a hematogenous mediation of the response.
Perenlei Enkhbaatar - One of the best experts on this subject based on the ideXlab platform.
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abstract 19670 adipose derived mesenchymal stem cells attenuate pulmonary microvascular hyperpermeability after smoke inhalation
Circulation, 2015Co-Authors: Koji Ihara, David N. Herndon, Satoshi Fukuda, Baigalmaa Enkhtaivan, Raul Trujillo, Ernesto Lopez, Hal K Hawkins, Donald S Prough, Perenlei EnkhbaatarAbstract:Pulmonary edema is a hallmark of acute respiratory distress syndrome (ARDS). Smoke inhalation causes ARDS, significantly increasing the mortality of burn patients. Mesenchymal stem cells (MSCs) exert potent anti-inflammatory properties. The goal of the present study was to test the safety and efficacy of MSCs in a well-characterized clinically relevant ovine model of ARDS. Methods: Female sheep (30-40 kg) were surgically prepared 5-7 days prior the study. ARDS was induced by cooled cotton smoke inhalation. Following the injury, sheep were ventilated, resuscitated with lactated Ringer’s solution and cardiopulmonary hemodynamics was monitored for 48 h in a conscious state. Pulmonary microvascular hyper-permeability was assessed by measuring Lung Lymph flow, extravascular Lung water content, protein in plasma and Lung Lymph. Sheep were randomly allocated to two groups: 1) MSCs: infused with 5 million/kg of intravenous MSCs over 30min starting 1 h post-injury, n=5; 2) control, treated with a vehicle in a similar pattern (200ml of PlasmaLyte A), n=5. Results: Lung Lymph flow, an index of pulmonary transvascular fluid flux was ~7-fold increased in control sheep compared to baseline. This was associated with a significant protein decrease in plasma and its increase in Lung Lymph. The treatment with MSCs significantly attenuated these changes (Table). Moreover, the treatment with MSCs almost reversed increased pulmonary vascular permeability index {(Lung Lymph proteinхLung Lymph flow)/plasma protein} and reduced Lung water content (Lung wet-to-dry weight ratio). Pulmonary gas exchange was significantly improved by MSCs (PaO2/FiO2 was 406±101 in MSCs and 262±127 in control at 24 hrs, p Conclusions: MSCs infusion was well tolerated. The results suggest that intravenous MSCs modulate pulmonary microvascular hyper-permeability and prevent onset of ARDS.
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pulmonary microvascular hyperpermeability and expression of vascular endothelial growth factor in smoke inhalation and pneumonia induced acute Lung injury
Burns, 2012Co-Authors: David N. Herndon, Matthias Lange, Yoshimitsu Nakano, Atsumori Hamahata, Lillian D. Traber, Daniel L Traber, Rhykka L Connelly, Frank C Schmalstieg, Perenlei EnkhbaatarAbstract:Abstract Introduction Acute Lung injury (ALI) and sepsis are major contributors to the morbidity and mortality of critically ill patients. The current study was designed further evaluate the mechanism of pulmonary vascular hyperpermeability in sheep with these injuries. Methods Sheep were randomized to a sham-injured control group ( n = 6) or ALI/sepsis group ( n = 7). The sheep in the ALI/sepsis group received inhalation injury followed by instillation of Pseudomonas aeruginosa into the Lungs. These groups were monitored for 24 h. Additional sheep ( n = 16) received the injury and Lung tissue was harvested at different time points to measure Lung wet/dry weight ratio, vascular endothelial growth factor (VEGF) mRNA and protein expression as well as 3-nitrotyrosine protein expression in Lung homogenates. Results The injury induced severe deterioration in pulmonary gas exchange, increases in Lung Lymph flow and protein content, and Lung water content ( P P Conclusions This study describes the time course of pulmonary microvascular hyperpermeability in a clinical relevant large animal model and may improve the experimental design of future studies.
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Predictive role of arterial carboxyhemoglobin concentrations in ovine burn and smoke inhalation-induced Lung injury.
Experimental Lung Research, 2011Co-Authors: Matthias Lange, Robert A. Cox, Perenlei Enkhbaatar, Elbert B. Whorton, Yoshimitsu Nakano, Atsumori Hamahata, Collette Jonkam, Aimalohi Esechie, Sanna Von Borzyskowski, Lillian D. TraberAbstract:Inhalation injury frequently occurs in burn patients and contributes to the morbidity and mortality of these injuries. Arterial carboxyhemoglobin has been proposed as an indicator of the severity of inhalation injury; however, the interrelation between arterial carboxyhemoglobin and histological alterations has not yet been investigated. Chronically instrumented sheep were subjected to a third degree burn of 40% of the total body surface area and inhalation of 48 breaths of cotton smoke. Carboxyhemoglobin was measured immediately after injury and correlated to clinical parameters of pulmonary function as well as histopathology scores from Lung tissue harvested 24 hours after the injury. The injury was associated with a significant decline in pulmonary oxygenation and increases in pulmonary shunting, Lung Lymph flow, wet/dry weight ratio, congestion score, edema score, inflammation score, and airway obstruction scores. Carboxyhemoglobin was negatively correlated to pulmonary oxygenation and positively correlated to pulmonary shunting, Lung Lymph flow, and Lung wet/dry weight ratio. No significant correlations could be detected between carboxyhemoglobin and histopathology scores and airway obstruction scores. Arterial carboxyhemoglobin in sheep with combined burn and inhalation injury are correlated with the degree of pulmonary failure and edema formation, but not with certain histological alterations including airway obstruction scores.
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positive end expiratory pressure ventilation increases extravascular Lung water due to a decrease in Lung Lymph flow
Anaesthesia and Intensive Care, 2006Co-Authors: Perenlei Enkhbaatar, D M Maybauer, Pekka Talke, M Westphal, M O Maybauer, L D Traber, N Morita, Daniel L TraberAbstract:Abstract Positive end-expiratory pressure (PEEP) is used to improve gas exchange, increase functional residual capacity, recruit air spaces, and decrease pulmonary shunt in patients suffering from respiratory failure. The effect of PEEP on extravascular Lung water (EVLW), however, is still not fully understood. This study was designed as a prospective laboratory experiment to evaluate the effects of PEEP on EVLW and pulmonary Lymph flow (QL) under physiologic conditions. Twelve adult sheep were operatively prepared to measure haemodynamics of the systemic and pulmonary circulation, and to assess EVLW In addition, the Lung Lymphatic duct was cannulated and a tracheostomy performed. The animals were then mechanically ventilated in the awake-state without end-expiratory pressure (PEEP 0). After a two-hour baseline period, PEEP was increased to 10 cmH2O for the duration of two hours, and then reduced back to 0 cmH2O. Cardiopulmonary variables, QL, and arterial blood gases were recorded intermittently; EVLW was determined two hours after each change in PEEP. The increase in PEEP resulted in a decrease in QL (7 +/- 1 vs 5 +/- 1 ml/h) and an increase in EVLW (498 +/- 40 vs 630 +/- 58 ml; P<0.05 each) without affecting cardiac output. As PEEP was decreased back to baseline, QL increased significantly (5 +/- 1 vs 10 +/- 2 ml/h), whereas EVLW returned back to baseline. This study suggests that institution of PEEP produces a reversible increase in EVLW that is linked to a decrease in QL.
Richard D. Bland - One of the best experts on this subject based on the ideXlab platform.
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Chronic Lung Injury in Preterm Lambs: Abnormalities of the Pulmonary Circulation and Lung Fluid Balance
Pediatric Research, 2000Co-Authors: Richard D. Bland, David P Carlton, Kurt H Albertine, Linda Kullama, Penny Davis, Soo-chul Cho, Beyong Il Kim, Marjanna Dahl, Niloufar TabatabaeiAbstract:Chronic Lung disease of early infancy, or bronchopulmonary dysplasia, is a frequent complication of prolonged mechanical ventilation after premature birth. Pulmonary hypertension and edema are common features of this condition, which is often attributed to long-term, repetitive overinflation of incompletely developed Lungs. The overall objective of this work was to examine the effects on the pulmonary circulation and Lung fluid balance of different ventilation strategies using large versus small inflation volumes in an animal model of bronchopulmonary dysplasia. We studied 16 newborn lambs that were delivered prematurely (124 ± 3 d gestation, term = 147 d) by cesarean section and mechanically ventilated for 3 to 4 wk. Ten lambs were ventilated at 20 breaths/min, yielding a tidal volume of 15 ± 5 mL/kg, and six lambs were ventilated at 60 breaths/min, yielding a tidal volume of 6 ± 2 mL/kg. All lambs received surfactant at birth and had subsequent surgery for closure of the ductus arteriosus and catheter placement to allow serial measurements of pulmonary vascular resistance and Lung Lymph flow. Chronic Lung injury, documented by serial chest radiographs and postmortem pathologic examination, developed in all lambs irrespective of the pattern of assisted ventilation. Pulmonary vascular resistance, which normally decreases during the month after birth at term, did not change significantly from the first to the last week of study. Lung Lymph flow, an index of net transvascular fluid filtration, increased with time in lambs that were ventilated at 20 breaths/min, but not in lambs ventilated at 60 breaths/min. Lymph protein concentration decreased with time, indicative of increased fluid filtration pressure, without evidence of a change in Lung vascular protein permeability. Postmortem studies showed interstitial Lung edema, increased pulmonary arteriolar smooth muscle and elastin, decreased numbers of small pulmonary arteries and veins, and decreased capillary surface density in distal Lung of chronically ventilated lambs compared with control lambs that were killed either 1 d (same postconceptional age) or 3 wk (same postnatal age) after birth at term. Thus, chronic Lung injury from prolonged mechanical ventilation after premature birth inhibits the normal postnatal decrease in pulmonary vascular resistance and leads to Lung edema from increased fluid filtration pressure. These abnormalities of the pulmonary circulation may contribute to the abnormal respiratory gas exchange that often exists in infants with bronchopulmonary dysplasia.
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increased pulmonary vascular filtration pressure does not alter Lung liquid secretion in fetal sheep
Journal of Applied Physiology, 1992Co-Authors: David P Carlton, Francis R Poulain, J J Cummings, Richard D. BlandAbstract:The purpose of this study was to determine whether an increase in pulmonary vascular filtration pressure affects net production of liquid within the lumen of the fetal Lung. We studied 14 chronically catheterized fetal lambs [130 +/- 3 (SD) days gestation] before, during, and after a 4-h rapid (500 ml/h) intravenous infusion of isotonic saline. In seven fetuses we measured pulmonary arterial and left atrial pressures, Lung Lymph flow, and protein osmotic pressures in plasma and Lymph. In eight lambs with a chronically implanted tracheal loop cannula, we measured the change in luminal Lung liquid volume over time by progressive dilution of tracheally instilled 125I-albumin, which stays within the Lung lumen. Saline infusion increased pulmonary vascular pressures by 2-3 mmHg and decreased the plasma-Lymph difference in protein osmotic pressure by 1 mmHg. Lung Lymph flow increased from 1.9 +/- 0.6 to 3.9 +/- 1.2 (SD) ml/h; net production of luminal Lung liquid did not change (12 +/- 5 to 12 +/- 6 ml/h). Thus an increase in net fluid filtration pressure in the pulmonary circulation, which was sufficient to double Lung Lymph flow, had no significant effect on luminal Lung liquid secretion in fetal sheep.
Bruce A. Harms - One of the best experts on this subject based on the ideXlab platform.
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Pulmonary capillary sieving of hetastarch is not altered by LPS-induced sepsis.
The Journal of Trauma: Injury Infection and Critical Care, 1999Co-Authors: Robert L. Conhaim, Kal E. Watson, Bruce Potenza, Bruce A. HarmsAbstract:BACKGROUND Gram-negative lipopolysaccharide (LPS) has been demonstrated to increase pulmonary capillary permeability as judged by the increased flow of protein-rich Lymph from the Lungs of sheep infused with LPS. This finding suggests that LPS-injured pulmonary capillaries might be less restrictive than uninjured capillaries to the filtration of large hetastarch molecules. Hetastarch has a broad molecular mass spectrum (35-1,500 kilodaltons (kDa)), and one way to test the restrictiveness of pulmonary capillaries is to measure the size of the largest hetastarch molecules that cross the microvascular barrier and enter the Lymph. To evaluate the effects of LPS, we compared hetastarch molecular distributions in the Lung Lymph of normal and LPS-injured sheep. METHODS Adult sheep (38.2 +/- 0.8 kg) were surgically prepared for the collection of Lung Lymph, with study initiation after a 5- to 7-day recovery period. Hetastarch (6%) was infused (10 mL/kg) 24 hours before study to allow for stabilization of the hetastarch molecular distribution. On the day of study, LPS (Escherichia coli lipopolysaccharide, 2 microg/kg; n = 6) was infused, and plasma and Lymph samples were collected for 12 hours. An additional group of animals not infused with LPS (n = 6) served as controls. Hetastarch molecular distributions in plasma and Lymph were measured by using high performance size exclusion chromatography. RESULTS In control sheep, the largest hetastarch molecules in Lymph averaged 861 +/- 18 kDa (mean +/- SEM) (plasma, 1,065 +/- 18 kDa). In LPS-treated sheep, the largest hetastarch molecules in Lymph averaged 845 +/- 19 kDa (not significant vs. normal) (plasma, 1,025 +/- 14 kDa). Hetastarch concentrations in plasma and Lung Lymph of normal sheep, respectively, were 0.61 +/- 0.05% and 0.34 +/- 0.07%. In LPS-treated sheep, hetastarch concentrations in plasma and Lymph were 0.56 +/- 0.08 (not significant vs. normal) and 0.29 +/- 0.07, respectively (p < or = 0.05). Lymph concentrations were lower after LPS because of increased Lymph flows (19.9 +/- 5.4 mL/30 min, compared with 3.6 +/- 0.8 mL/30 min in normal sheep). CONCLUSION Our results suggest that LPS does not alter the diameter of the largest pores perforating the walls of pulmonary capillaries. Rather, the number of these pores in the capillary wall appears to be increased. This increase would explain why Lymph flows rise after LPS with little change in the Lymph protein concentration. Our results are also consistent with a filtration model in which capillaries are assumed to be perforated by small pores (protein reflection coefficient = 1) as well as large pores (protein reflection coefficient = 0).
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Lung Lymph oncotic pressure may not modulate pulmonary vascular filtration in sheep.
American journal of respiratory and critical care medicine, 1997Co-Authors: Robert L. Conhaim, Gregory A. Myers, A M Mcgrath, S D Cooler, David A. Deangeles, Bruce A. HarmsAbstract:We tested the hypothesis that plasma oncotic pressure alone, not the plasma-to-Lymph oncotic pressure difference, modulates pulmonary transvascular fluid filtration. To do this we measured Lung Lymph flow after raising left atrial pressure (by inflating a balloon) in sheep that were receiving a continuous (32 h) infusion of dextran 40. For comparison, we also raised left atrial pressure elevation, plasma oncotic pressures in dextran and control sheep, respectively, were 39.5 +/- 4.5 and 17.7 +/- 2.2 mm Hg; plasma-to-Lymph oncotic pressure gradients, respectively, were 4.4 +/- 0.6 and 4.4 +/- 0.6 mm Hg. Left atrial pressure elevation during dextran infusion increased Lung Lymph flow by a factor of 2.4 +/- 0.4, compared with a factor of 4.2 +/- 2.3 in control sheep. Thus, left atrial pressure elevation increased Lymph flow less in dextran-treated animals than in control animals, even though the plasma-to-Lymph oncotic pressure gradients were equal. This suggests that plasma oncotic pressure alone may be a more important determinant of pulmonary transvascular fluid filtration than the plasma-to-Lymph oncotic pressure difference.
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Molecular distribution of hetastarch in plasma and Lung Lymph of unanesthetized sheep
American Journal of Respiratory and Critical Care Medicine, 1997Co-Authors: V A Korent, Robert L. Conhaim, A M Mcgrath, David A. Deangeles, Bruce A. HarmsAbstract:We used high performance size exclusion chromatography (HPSEC) to measure concentrations and molecular masses of hetastarch (Het) in plasma and Lung Lymph of unanesthetized sheep. Our goal was to assess the osmotic effectiveness of Het in the pulmonary circulation as judged by its exclusion from Lung Lymph. Sheep (n = 5) received 35 ml/kg of Het (6%) over 90 min. At the end of the infusion, Het concentrations in plasma reached a peak value of 2.9 +/- 0.1% (mean +/- SD). Lymph concentrations reached a peak value of 1.3 +/- 0.3% at 4.5 h. Het molecular masses in plasma averaged 650 +/- 36 kD at 90 min, but ranged from 31 to 2,942 +/- 187 kD. Masses in Lung Lymph averaged 373 +/- 71 kD, and ranged from 19 +/- 2 to 1,693 +/- 514 kD (p < or = 0.05 vs. plasma). Het contributed 6.7 +/- 1.5 mm Hg to the plasma macromolecular osmotic pressure, and 3.7 +/- 1.8 mm Hg to the Lymph osmotic pressure. Despite the fact that Het has the largest molecular mass of any of the current macromolecular plasma volume expanders, w...
Daniel L Traber - One of the best experts on this subject based on the ideXlab platform.
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pulmonary microvascular hyperpermeability and expression of vascular endothelial growth factor in smoke inhalation and pneumonia induced acute Lung injury
Burns, 2012Co-Authors: David N. Herndon, Matthias Lange, Yoshimitsu Nakano, Atsumori Hamahata, Lillian D. Traber, Daniel L Traber, Rhykka L Connelly, Frank C Schmalstieg, Perenlei EnkhbaatarAbstract:Abstract Introduction Acute Lung injury (ALI) and sepsis are major contributors to the morbidity and mortality of critically ill patients. The current study was designed further evaluate the mechanism of pulmonary vascular hyperpermeability in sheep with these injuries. Methods Sheep were randomized to a sham-injured control group ( n = 6) or ALI/sepsis group ( n = 7). The sheep in the ALI/sepsis group received inhalation injury followed by instillation of Pseudomonas aeruginosa into the Lungs. These groups were monitored for 24 h. Additional sheep ( n = 16) received the injury and Lung tissue was harvested at different time points to measure Lung wet/dry weight ratio, vascular endothelial growth factor (VEGF) mRNA and protein expression as well as 3-nitrotyrosine protein expression in Lung homogenates. Results The injury induced severe deterioration in pulmonary gas exchange, increases in Lung Lymph flow and protein content, and Lung water content ( P P Conclusions This study describes the time course of pulmonary microvascular hyperpermeability in a clinical relevant large animal model and may improve the experimental design of future studies.
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inhibition of Lung permeability changes after burn and smoke inhalation by an anti interleukin 8 antibody in sheep
Surgery Today, 2009Co-Authors: Hiroyuki Sakurai, Frank C Schmalstieg, Kazutaka Soejima, Motohiro Nozaki, Daniel L TraberAbstract:To evaluate the effects of a monoclonal antibody against interleukin-8 (K2.2) on the microvascular fluid flux after combined injury by burn and smoke inhalation. Fourteen sheep were prepared surgically by placing a Lung Lymph catheter and a flank Lymph catheter to examine the microvascular fluid flux. After a recovery period, they were subjected to a combined injury of 40% third-degree burns on the flank and smoke inhalation. This combined injury induced a rapid increase in burned tissue Lymph flow (b-QL) and a delayed-onset increase in Lung Lymph flow (l-QL). The initial increase in b-QL was associated with an elevation of the Lymph-to-plasma oncotic pressure ratio, which led to a predominant increase in the burned tissue permeability index (b-PI). Pretreatment with K2.2 had no effect on the permeability change seen in the burned tissue; however, the Lung permeability changes were attenuated by pretreatment with K2.2. These findings indicate that the pathogenesis of the increase in microvascular fluid flux seen after the combined injury differs in burned tissue and the Lung.
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positive end expiratory pressure ventilation increases extravascular Lung water due to a decrease in Lung Lymph flow
Anaesthesia and Intensive Care, 2006Co-Authors: Perenlei Enkhbaatar, D M Maybauer, Pekka Talke, M Westphal, M O Maybauer, L D Traber, N Morita, Daniel L TraberAbstract:Abstract Positive end-expiratory pressure (PEEP) is used to improve gas exchange, increase functional residual capacity, recruit air spaces, and decrease pulmonary shunt in patients suffering from respiratory failure. The effect of PEEP on extravascular Lung water (EVLW), however, is still not fully understood. This study was designed as a prospective laboratory experiment to evaluate the effects of PEEP on EVLW and pulmonary Lymph flow (QL) under physiologic conditions. Twelve adult sheep were operatively prepared to measure haemodynamics of the systemic and pulmonary circulation, and to assess EVLW In addition, the Lung Lymphatic duct was cannulated and a tracheostomy performed. The animals were then mechanically ventilated in the awake-state without end-expiratory pressure (PEEP 0). After a two-hour baseline period, PEEP was increased to 10 cmH2O for the duration of two hours, and then reduced back to 0 cmH2O. Cardiopulmonary variables, QL, and arterial blood gases were recorded intermittently; EVLW was determined two hours after each change in PEEP. The increase in PEEP resulted in a decrease in QL (7 +/- 1 vs 5 +/- 1 ml/h) and an increase in EVLW (498 +/- 40 vs 630 +/- 58 ml; P<0.05 each) without affecting cardiac output. As PEEP was decreased back to baseline, QL increased significantly (5 +/- 1 vs 10 +/- 2 ml/h), whereas EVLW returned back to baseline. This study suggests that institution of PEEP produces a reversible increase in EVLW that is linked to a decrease in QL.
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unilateral smoke inhalation in sheep effect on left Lung Lymph flow with right Lung injury
American Journal of Physiology-regulatory Integrative and Comparative Physiology, 1996Co-Authors: Yuji Kikuchi, David N. Herndon, L D Traber, Daniel L TraberAbstract:We previously reported that smoke inhalation to the right Lung will result in damage to the air-insufflated left Lung. In this study we confirm these findings and determine whether this injury is associated with an elevation in Lung Lymph flow and pulmonary microvascular permeability to protein as indexed by changes in reflection coefficient. Sheep (n = 12) were surgically prepared by placement of a Swan-Ganz catheter and pneumatic occluders on all pulmonary veins and the left pulmonary artery. The left Lung Lymphatic was selectively cannulated as shown previously (Y. Kikuchi, H. Nakazawa, and D. Traber. Am. J. Physiol. 269 (Regulatory Integrative Comp. Physiol. 38): R943-R947, 1995). All afferent Lymphatics from the right Lung were severed, and the right pulmonary ligament was sectioned. The caudal end of the Lymph node was sectioned to remove systemic Lymph contamination. The sheep were studied in the unanesthetized state 7 days later. To ensure that Lymph flow was exclusively from the left Lung (QLL), right pulmonary microvascular pressure was increased, a procedure that resulted in little or no change in QLL, as was previously shown. The sheep were then anesthetized, and a Carlens tube was positioned to allow separate ventilation of the right and left Lung. The right Lungs of five sheep and the left Lungs of two sheep were insufflated with cotton smoke. Insufflation of the left Lung with cotton smoke produced a fourfold increase in QLL that began 4 h after insult. Insufflation of the right Lung with smoke led to a doubling of QLL that began 12 h after insult. Changes in QLL were associated with increased microvascular permeability, as indexed by the reflection coefficient. Control sheep (air insufflated into both Lungs, n = 5) showed no change in QLL. Injury to the right Lung resulted in damage to the left air-insufflated Lung, suggesting a hematogenous mediation of the response.
