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Torsten Richter - One of the best experts on this subject based on the ideXlab platform.
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Causative treatment of Acid Aspiration induced acute lung injury - Recent trends from animal experiments and critical perspective.
Clinical hemorheology and microcirculation, 2018Co-Authors: Johannes Gramatté, Jens Pietzsch, Ralf Bergmann, Torsten RichterAbstract:Aspiration of low-pH gastric fluid leads to an initial pneumonitis, which may become complicated by subsequent pneumonia or acute respiratory distress syndrome. Current treatment is at best supportive, but there is growing experimental evidence on the significant contribution of both neutrophils and platelets in the development of this inflammatory pulmonary reaction, a condition that can be attenuated by several medicinal products. This review aims to summarize novel findings in experimental models on pathomechanisms after an Acid-Aspiration event. Given the clinical relevance, specific emphasis is put on deduced potential experimental therapeutic approaches, which make use of the characteristic alteration of microcirculation in the injured lung.
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Effects of pulmonary Acid Aspiration on the regional pulmonary blood flow within the first hour after injury: An observational study in rats1
Clinical hemorheology and microcirculation, 2015Co-Authors: Torsten Richter, Ralf Bergmann, Jens Pietzsch, Michael P. Mueller, Thea KochAbstract:INTRODUCTION Gastric Aspiration events are recognized as a major cause of pneumonitis and the development of acute respiratory distress syndrome. The first peak in the inflammatory response has been observed one hour after Acid-induced lung injury in rats. The spatial pulmonary blood flow (PBF) distribution after an Acid Aspiration event within this time frame has not been adequately studied. We determined therefore PBF pattern within the first hour after Acid Aspiration. METHODS Anesthetized, spontaneous breathing rats (n = 8) underwent unilateral endobronchial hydrochlorid Acid instillation so that the PBF distributions between the injured and non-injured lungs could be compared. The signal intensity of the lung parenchyma after injury was measured by magnetic resonance tomography. PBF distribution was determined by measuring the concentration of [68Ga]-radiolabeled microspheres using positron emission tomography. RESULTS Following Acid Aspiration, magnetic resonance images revealed increased signal intensity in the injured regions accompanied by reduced oxygenation. PBF was increased in all injured lungs (171 [150; 196], median [25%; 75%]) compared to the blood flow in all uninjured lungs (141 [122; 159], P = 0.0078). CONCLUSIONS From the first minute until fifty minutes after Acid-induced acute lung injury, the PBF was consistently increased in the injured lung. These blood flow elevation was accompanied by significant hypoxemia.
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Reduced pulmonary blood flow in regions of injury 2 hours after Acid Aspiration in rats
BMC Anesthesiology, 2015Co-Authors: Torsten Richter, Ralf Bergmann, Guido Musch, Jens Pietzsch, Thea KochAbstract:Background Aspiration-induced lung injury can decrease gas exchange and increase mortality. Acute lung injury following Acid Aspiration is characterized by elevated pulmonary blood flow (PBF) in damaged lung areas in the early inflammation stage. Knowledge of PBF patterns after Acid Aspiration is important for targeting intravenous treatments. We examined PBF in an experimental model at a later stage (2 hours after injury). Methods Anesthetized Wistar-Unilever rats (n = 5) underwent unilateral endobronchial instillation of hydrochloric Acid. The PBF distribution was compared between injured and uninjured sides and with that of untreated control animals (n = 6). Changes in lung density after injury were measured using computed tomography (CT). Regional PBF distribution was determined quantitatively in vivo 2 hours after Acid instillation by measuring the concentration of [^68Ga]-radiolabeled microspheres using positron emission tomography. Results CT scans revealed increased lung density in areas of Acid Aspiration. Lung injury was accompanied by impaired gas exchange. Acid Aspiration decreased the arterial pressure of oxygen from 157 mmHg [139;165] to 74 mmHg [67;86] at 20 minutes and tended toward restoration to 109 mmHg [69;114] at 110 minutes ( P
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reduced pulmonary blood flow in regions of injury 2 hours after Acid Aspiration in rats
BMC Anesthesiology, 2015Co-Authors: Torsten Richter, Ralf Bergmann, Guido Musch, Jens Pietzsch, Thea KochAbstract:Background: Aspiration-induced lung injury can decrease gas exchange and increase mortality. Acute lung injury following Acid Aspiration is characterized by elevated pulmonary blood flow (PBF) in damaged lung areas in the early inflammation stage. Knowledge of PBF patterns after Acid Aspiration is important for targeting intravenous treatments. We examined PBF in an experimental model at a later stage (2 hours after injury). Methods: Anesthetized Wistar-Unilever rats (n = 5) underwent unilateral endobronchial instillation of hydrochloric Acid. The PBF distribution was compared between injured and uninjured sides and with that of untreated control animals (n = 6). Changes in lung density after injury were measured using computed tomography (CT). Regional PBF distribution was determined quantitatively in vivo 2 hours after Acid instillation by measuring the concentration of [ 68 Ga]-radiolabeled microspheres using positron emission tomography. Results: CT scans revealed increased lung density in areas of Acid Aspiration. Lung injury was accompanied by impaired gas exchange. Acid Aspiration decreased the arterial pressure of oxygen from 157 mmHg [139;165] to 74 mmHg [67;86] at 20 minutes and tended toward restoration to 109 mmHg [69;114] at 110 minutes (P < 0.001). The PBF ratio of the middle region of the injured versus uninjured lungs of the Aspiration group (0.86 [0.7;0.9], median [25%;75%]) was significantly lower than the PBF ratio in the left versus right lung of the control group (1.02 [1.0;1.05]; P = 0.016). Conclusions: The PBF pattern 2 hours after Aspiration-induced lung injury showed a redistribution of PBF away from injured regions that was likely responsible for the partial recovery from hypoxemia over time. Treatments given intravenously 2 hours after Acid-induced lung injury may not preferentially reach the injured lung regions, contrary to what occurs during the first hour of inflammation.
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pulmonary blood flow increases in damaged regions directly after Acid Aspiration in rats
Anesthesiology, 2013Co-Authors: Torsten Richter, Ralf Bergmann, Jens Pietzsch, Lilla Knels, Frank Hofheinz, Michael Kasper, Martin Deile, M Ragaller, Thea KochAbstract:BACKGROUND: After gastric Aspiration events, patients are at risk of pulmonary dysfunction and the development of severe acute lung injury and acute respiratory distress syndrome, which may contribute to the development of an inflammatory reaction. The authors' aim in the current study was to investigate the role of the spatial distribution of pulmonary blood flow in the pathogenesis of pulmonary dysfunction during the early stages after Acid Aspiration. METHODS: The authors analyzed the pulmonary distribution of radiolabeled microspheres in normal (n = 6) and injured (n = 12) anesthetized rat lungs using positron emission tomography, computed tomography, and histological examination. RESULTS: Injured regions demonstrate increased pulmonary blood flow in association with reduced arterial pressure and the deterioration of arterial oxygenation. After Acid Aspiration, computed tomography scans revealed that lung density had increased in the injured regions and that these regions colocalized with areas of increased blood flow. The Acid was instilled into the middle and basal regions of the lungs. The blood flow was significantly increased to these regions compared with the blood flow to uninjured lungs in the control animals (middle region: 1.23 [1.1; 1.4] (median [25%; 75%]) vs. 1.04 [1.0; 1.1] and basal region: 1.25 [1.2; 1.3] vs. 1.02 [1.0; 1.05], respectively). The increase in blood flow did not seem to be due to vascular leakage into these injured areas. CONCLUSIONS: The data suggest that 10 min after Acid Aspiration, damaged areas are characterized by increased pulmonary blood flow. The results may impact further treatment strategies, such as drug targeting.
Elie Fadel - One of the best experts on this subject based on the ideXlab platform.
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Exogenous surfactant attenuates lung injury from gastric-Acid Aspiration during ex vivo reconditioning in pigs.
Transplantation, 2014Co-Authors: Theresa Khalifé-hocquemiller, Edouard Sage, Peter Dorfmüller, Sacha Mussot, Daniel Le Houérou, Saadia Eddahibi, Elie FadelAbstract:BACKGROUND Lung injury (LI) due to gastric-Acid Aspiration is associated with poor posttransplantation outcomes. We investigated the effects of ex vivo lung perfusion (EVLP) reconditioning and surfactant administration on LI due to gastric-Acid Aspiration. METHODS Thirty piglets were allocated at random to five groups: the lungs were studied 24 hr after gastric juice-induced LI of the left lower lobe (LLL), LI followed by EVLP (4 hr), or LI followed by LLL surfactant lavage immediately before EVLP; sham animals were studied 24 hr after saline infusion alone or followed by EVLP. Gross anatomy, hemodynamics, and aerodynamics were evaluated; neutrophil and bacterial counts were determined in bronchoalveolar lavage (BAL) fluid and blood. LLLs were evaluated based on a semi-quantitative histologic score, apoptotic cell death (TUNEL), and inflammatory cytokine levels. RESULTS The sham and sham-EVLP groups were not significantly different. Compared with sham, LI animals had irreversible atelectasis, higher lung infection rates (P
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exogenous surfactant attenuates lung injury from gastric Acid Aspiration during ex vivo reconditioning in pigs
Transplantation, 2014Co-Authors: Theresa Khalifehocquemiller, Edouard Sage, Peter Dorfmüller, Sacha Mussot, Daniel Le Houérou, Saadia Eddahibi, Elie FadelAbstract:BACKGROUND Lung injury (LI) due to gastric-Acid Aspiration is associated with poor posttransplantation outcomes. We investigated the effects of ex vivo lung perfusion (EVLP) reconditioning and surfactant administration on LI due to gastric-Acid Aspiration. METHODS Thirty piglets were allocated at random to five groups: the lungs were studied 24 hr after gastric juice-induced LI of the left lower lobe (LLL), LI followed by EVLP (4 hr), or LI followed by LLL surfactant lavage immediately before EVLP; sham animals were studied 24 hr after saline infusion alone or followed by EVLP. Gross anatomy, hemodynamics, and aerodynamics were evaluated; neutrophil and bacterial counts were determined in bronchoalveolar lavage (BAL) fluid and blood. LLLs were evaluated based on a semi-quantitative histologic score, apoptotic cell death (TUNEL), and inflammatory cytokine levels. RESULTS The sham and sham-EVLP groups were not significantly different. Compared with sham, LI animals had irreversible atelectasis, higher lung infection rates (P<0.0001) and BAL neutrophil percentages (P<0.0001), lower PaO2 (P=0.0006), higher IL-1 (P=0.022) and IL-8 (P=0.006), higher apoptotic cell percentages (P=0.007), and worse histologic severity scores (P<0.0001). EVLP alone did not improve these findings. Adding surfactant before EVLP returned PaO2, pulmonary vascular resistance, and apoptotic-cell percentage to sham-EVLP values but only partially improved the histologic severity score. CONCLUSION Local surfactant infusion immediately before EVLP improved the function of donor lungs injured by gastric juice Aspiration. This strategy may hold promise for decreasing the shortage of donor lungs.
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Lung Injuries Induced by Gastric Acid Aspiration Are Attenuated by Exogenous Surfactant during Ex Vivo Reconditioning in Pigs
The Journal of Heart and Lung Transplantation, 2013Co-Authors: T. Khalife, Edouard Sage, Peter Dorfmüller, Saadia Eddahibi, Elie FadelAbstract:Purpose Gastric Acid Aspiration is a common reason for rejecting lungs for transplantation as it is associated with increased risks of graft dysfunction. We investigated Ex vivo lung perfusion (EVLP) reconditioning on lung injuries due to gastric Acid Aspiration and effects of surfactant administration. Methods and Materials 30 piglets were allocated to 5 groups. Aspiration lung injury (LI) was induced by infusing 1 ml/kg of autologous gastric juice into the left lower lobe (LLL). 24 hours later, the lungs were studied (LI group) or reconditioned using EVLP for 4 hours without additional treatment (LI-EVLP group) or after surfactant lavage (curosurf 100 mg/kg) in the LLL (Surf-EVLP group). Sham animals were studied 24 h after saline infusion and Sham-EVLP animals 24 h after saline infusion followed by 4 h of EVLP. Gross anatomy, hemodynamics, and aerodynamics were evaluated; neutrophil and bacterial counts in bronchoalveolar lavage (BAL) fluid and blood were determined. LLLs were evaluated by tissue wet/dry ratio; histology (semi-quantitative severity score); apoptotic cell using TUNEL; and IL-1, IL-6, IL-8, IL-10, and TNFa protein levels. Results There were no significant differences between the Sham and Sham-EVLP groups. Compared to Sham, LI animals had irreversible atelectasis, a higher lung infection rate (P 2 (P=0.0006), higher IL1 (P=0.022) and IL8 (P=0.006) levels and apoptotic cell percentage (P=0.007), and worse histology severity score (P Conclusions Although 4 hours EVLP worsened LI due to gastric Acid Aspiration, when preceded by local infusion of surfactant it allowed complete PaO2 and partial histology recovery.
Thea Koch - One of the best experts on this subject based on the ideXlab platform.
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Effects of pulmonary Acid Aspiration on the regional pulmonary blood flow within the first hour after injury: An observational study in rats1
Clinical hemorheology and microcirculation, 2015Co-Authors: Torsten Richter, Ralf Bergmann, Jens Pietzsch, Michael P. Mueller, Thea KochAbstract:INTRODUCTION Gastric Aspiration events are recognized as a major cause of pneumonitis and the development of acute respiratory distress syndrome. The first peak in the inflammatory response has been observed one hour after Acid-induced lung injury in rats. The spatial pulmonary blood flow (PBF) distribution after an Acid Aspiration event within this time frame has not been adequately studied. We determined therefore PBF pattern within the first hour after Acid Aspiration. METHODS Anesthetized, spontaneous breathing rats (n = 8) underwent unilateral endobronchial hydrochlorid Acid instillation so that the PBF distributions between the injured and non-injured lungs could be compared. The signal intensity of the lung parenchyma after injury was measured by magnetic resonance tomography. PBF distribution was determined by measuring the concentration of [68Ga]-radiolabeled microspheres using positron emission tomography. RESULTS Following Acid Aspiration, magnetic resonance images revealed increased signal intensity in the injured regions accompanied by reduced oxygenation. PBF was increased in all injured lungs (171 [150; 196], median [25%; 75%]) compared to the blood flow in all uninjured lungs (141 [122; 159], P = 0.0078). CONCLUSIONS From the first minute until fifty minutes after Acid-induced acute lung injury, the PBF was consistently increased in the injured lung. These blood flow elevation was accompanied by significant hypoxemia.
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Reduced pulmonary blood flow in regions of injury 2 hours after Acid Aspiration in rats
BMC Anesthesiology, 2015Co-Authors: Torsten Richter, Ralf Bergmann, Guido Musch, Jens Pietzsch, Thea KochAbstract:Background Aspiration-induced lung injury can decrease gas exchange and increase mortality. Acute lung injury following Acid Aspiration is characterized by elevated pulmonary blood flow (PBF) in damaged lung areas in the early inflammation stage. Knowledge of PBF patterns after Acid Aspiration is important for targeting intravenous treatments. We examined PBF in an experimental model at a later stage (2 hours after injury). Methods Anesthetized Wistar-Unilever rats (n = 5) underwent unilateral endobronchial instillation of hydrochloric Acid. The PBF distribution was compared between injured and uninjured sides and with that of untreated control animals (n = 6). Changes in lung density after injury were measured using computed tomography (CT). Regional PBF distribution was determined quantitatively in vivo 2 hours after Acid instillation by measuring the concentration of [^68Ga]-radiolabeled microspheres using positron emission tomography. Results CT scans revealed increased lung density in areas of Acid Aspiration. Lung injury was accompanied by impaired gas exchange. Acid Aspiration decreased the arterial pressure of oxygen from 157 mmHg [139;165] to 74 mmHg [67;86] at 20 minutes and tended toward restoration to 109 mmHg [69;114] at 110 minutes ( P
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reduced pulmonary blood flow in regions of injury 2 hours after Acid Aspiration in rats
BMC Anesthesiology, 2015Co-Authors: Torsten Richter, Ralf Bergmann, Guido Musch, Jens Pietzsch, Thea KochAbstract:Background: Aspiration-induced lung injury can decrease gas exchange and increase mortality. Acute lung injury following Acid Aspiration is characterized by elevated pulmonary blood flow (PBF) in damaged lung areas in the early inflammation stage. Knowledge of PBF patterns after Acid Aspiration is important for targeting intravenous treatments. We examined PBF in an experimental model at a later stage (2 hours after injury). Methods: Anesthetized Wistar-Unilever rats (n = 5) underwent unilateral endobronchial instillation of hydrochloric Acid. The PBF distribution was compared between injured and uninjured sides and with that of untreated control animals (n = 6). Changes in lung density after injury were measured using computed tomography (CT). Regional PBF distribution was determined quantitatively in vivo 2 hours after Acid instillation by measuring the concentration of [ 68 Ga]-radiolabeled microspheres using positron emission tomography. Results: CT scans revealed increased lung density in areas of Acid Aspiration. Lung injury was accompanied by impaired gas exchange. Acid Aspiration decreased the arterial pressure of oxygen from 157 mmHg [139;165] to 74 mmHg [67;86] at 20 minutes and tended toward restoration to 109 mmHg [69;114] at 110 minutes (P < 0.001). The PBF ratio of the middle region of the injured versus uninjured lungs of the Aspiration group (0.86 [0.7;0.9], median [25%;75%]) was significantly lower than the PBF ratio in the left versus right lung of the control group (1.02 [1.0;1.05]; P = 0.016). Conclusions: The PBF pattern 2 hours after Aspiration-induced lung injury showed a redistribution of PBF away from injured regions that was likely responsible for the partial recovery from hypoxemia over time. Treatments given intravenously 2 hours after Acid-induced lung injury may not preferentially reach the injured lung regions, contrary to what occurs during the first hour of inflammation.
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pulmonary blood flow increases in damaged regions directly after Acid Aspiration in rats
Anesthesiology, 2013Co-Authors: Torsten Richter, Ralf Bergmann, Jens Pietzsch, Lilla Knels, Frank Hofheinz, Michael Kasper, Martin Deile, M Ragaller, Thea KochAbstract:BACKGROUND: After gastric Aspiration events, patients are at risk of pulmonary dysfunction and the development of severe acute lung injury and acute respiratory distress syndrome, which may contribute to the development of an inflammatory reaction. The authors' aim in the current study was to investigate the role of the spatial distribution of pulmonary blood flow in the pathogenesis of pulmonary dysfunction during the early stages after Acid Aspiration. METHODS: The authors analyzed the pulmonary distribution of radiolabeled microspheres in normal (n = 6) and injured (n = 12) anesthetized rat lungs using positron emission tomography, computed tomography, and histological examination. RESULTS: Injured regions demonstrate increased pulmonary blood flow in association with reduced arterial pressure and the deterioration of arterial oxygenation. After Acid Aspiration, computed tomography scans revealed that lung density had increased in the injured regions and that these regions colocalized with areas of increased blood flow. The Acid was instilled into the middle and basal regions of the lungs. The blood flow was significantly increased to these regions compared with the blood flow to uninjured lungs in the control animals (middle region: 1.23 [1.1; 1.4] (median [25%; 75%]) vs. 1.04 [1.0; 1.1] and basal region: 1.25 [1.2; 1.3] vs. 1.02 [1.0; 1.05], respectively). The increase in blood flow did not seem to be due to vascular leakage into these injured areas. CONCLUSIONS: The data suggest that 10 min after Acid Aspiration, damaged areas are characterized by increased pulmonary blood flow. The results may impact further treatment strategies, such as drug targeting.
Herbert B. Hechtman - One of the best experts on this subject based on the ideXlab platform.
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Sialyl Lewisx hybridized complement receptor type 1 moderates Acid Aspiration injury
American journal of physiology. Lung cellular and molecular physiology, 2001Co-Authors: Constantinos Kyriakides, William G. Austen, Yong Wang, Joanne Favuzza, Francis D. Moore, Lester Kobzik, Herbert B. HechtmanAbstract:The potentially enhanced anti-inflammatory effects of the sialyl Lewisx(sLex)-decorated version of soluble complement receptor type 1 (sCR1) in moderating Acid Aspiration injury are examined. HCl w...
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Mast cells mediate complement activation after Acid Aspiration.
Shock (Augusta Ga.), 2001Co-Authors: Constantinos Kyriakides, William G. Austen, Yong Wang, Joanne Favuzza, Francis D. Moore, Lester Kobzik, Herbert B. HechtmanAbstract:A significant role for the alternative complement pathway in Acid Aspiration has been demonstrated by the observation that C3 but not C4 genetic knockout mice are protected from permeability edema. Using mast cell-deficient mice (W/W v ), we tested the hypothesis that mast cells mediate complement activation after Acid Aspiration. Tracheostomy tubes were placed in anesthetized mice and 2 mUkg 0.1 N HCL was instilled in the trachea. After 4 h, extravasation of 125 I-albumin was used to calculate lung vascular permeability. The serum alternative complement pathway hemolytic activity was examined, and lung immunohistochemistry was performed. Lung permeability in W/W v mice was 62% less than that of mast cell sufficient (+/+) animals and similar to +/+ mice treated with the chymase inhibitor chymostatin (65% decrease). Treatment of +/+ mice with D-PRO 2 , D-TRP 7,9 -Substance P, an antagonist to the neuropeptide substance P, reduced injury by 66%. Serum complement hemolytic activity was intact in injured W/W v mice and +/+ animals treated with chymostatin or dpdt-sp, but was decreased to 65% in the injured untreated +/+ group. Alveolar C3 deposition was intense in injured untreated +/+ mice but absent in the other groups. We interpret these data to indicate that mast cells mediate complement activation, via chymase degranulation, after Acid Aspiration. This mast cell activity likely is regulated by the release of substance P.
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The Presence of v-abl-transformed V3 Mast Cells in the Lungs Augments Pulmonary Vascular Permeability to Acid Aspiration
The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society, 2001Co-Authors: Chandrika Mukundan, Herbert B. Hechtman, Michael F. Gurish, K. Frank Austen, Daniel S. FriendAbstract:Acid Aspiration causes pulmonary vascular permeability and PMN sequestration. By increasing pulmonary mast cells through adoptive transfer of v-abl-transformed mast cells (V3MCs) into BALB/c mice, we now show that the greater mast cell number in the lung is associated with increased pulmonary injury.
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Endothelial selectin blockade attenuates lung permeability of experimental Acid Aspiration.
Surgery, 2000Co-Authors: Constantinos Kyriakides, William G. Austen, Yong Wang, Joanne Favuzza, Francis D. Moore, Herbert B. HechtmanAbstract:Abstract Background: A central role for the polymorphonuclear leukocyte (PMN) in experimental Acid Aspiration has been demonstrated by the observation that PMN depletion reduced pulmonary vascular permeability. This study investigates the role of recombinant soluble P-selectin glycoprotein ligand-immunoglobulin fusion protein (rPSGL-Ig), a P- and E-selectin antagonist in moderating Acid Aspiration lung injury. Methods: Tracheostomy tubes were placed in male C57BL/6 mice and 0.1 N HCl was instilled into the trachea at 2 mL/kg after intravenous injection of 125 I-albumin. After 4 hours the lung vascular permeability index (PI) and PMN accumulation in the bronchoalveolar lavage fluid were assessed. Results: PI in neutropenic mice was 63% reduced compared with the untreated group and similar to the PI of mice treated with 1 mg/kg rPSGL-Ig before Acid Aspiration. PMN count of 19 ± 5 in the bronchoalveolar lavage fluid in rPSGL-Ig treated mice was significantly less than the untreated group PMN count of 586 ± 72. The respective PI in mice treated with rPSGL-Ig½ hour and 1 hour after Acid Aspiration was 45% and 39% reduced compared with the untreated group. Conclusions: Endothelial selectin blockade is as effective as PMN depletion in moderating Acid Aspiration induced lung permeability. Delayed antiselectin therapy can decrease lung injury. (Surgery 2000;128:327-31.)
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Membrane attack complex of complement and neutrophils mediate the injury of Acid Aspiration.
Journal of applied physiology (Bethesda Md. : 1985), 1999Co-Authors: Constantinos Kyriakides, William G. Austen, Yong Wang, Joanne Favuzza, Francis D. Moore, Lester Kobzik, Herbert B. HechtmanAbstract:A significant role for the alternative complement pathway in Acid Aspiration has been demonstrated by the observation that C3 genetic knockout mice are protected from injury. Utilizing C5-deficient mice, we now test the role of the terminal complement components in mediating injury. Lung permeability in C5-deficient mice was 64% less than in wild-type animals and was similar to wild-type mice treated with soluble complement receptor type 1, which gave a 67% protection. Injury was fully restored in C5-deficient mice reconstituted with wild-type serum. The role of neutrophils was established in immunodepleted wild-type animals that showed a 58% protection. Injury was further reduced (90%) with the addition of soluble complement receptor type 1, indicating an additive effect of neutrophils and complement. Similarly, an additional protection was noted in C5-deficient neutropenic mice, indicating that neutrophil-mediated injury does not require C5a. Thus Acid Aspiration injury is mediated by the membrane attack complex and neutrophils. Neutrophil activity is independent of C5a.
Jens Pietzsch - One of the best experts on this subject based on the ideXlab platform.
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Causative treatment of Acid Aspiration induced acute lung injury - Recent trends from animal experiments and critical perspective.
Clinical hemorheology and microcirculation, 2018Co-Authors: Johannes Gramatté, Jens Pietzsch, Ralf Bergmann, Torsten RichterAbstract:Aspiration of low-pH gastric fluid leads to an initial pneumonitis, which may become complicated by subsequent pneumonia or acute respiratory distress syndrome. Current treatment is at best supportive, but there is growing experimental evidence on the significant contribution of both neutrophils and platelets in the development of this inflammatory pulmonary reaction, a condition that can be attenuated by several medicinal products. This review aims to summarize novel findings in experimental models on pathomechanisms after an Acid-Aspiration event. Given the clinical relevance, specific emphasis is put on deduced potential experimental therapeutic approaches, which make use of the characteristic alteration of microcirculation in the injured lung.
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Effects of pulmonary Acid Aspiration on the regional pulmonary blood flow within the first hour after injury: An observational study in rats1
Clinical hemorheology and microcirculation, 2015Co-Authors: Torsten Richter, Ralf Bergmann, Jens Pietzsch, Michael P. Mueller, Thea KochAbstract:INTRODUCTION Gastric Aspiration events are recognized as a major cause of pneumonitis and the development of acute respiratory distress syndrome. The first peak in the inflammatory response has been observed one hour after Acid-induced lung injury in rats. The spatial pulmonary blood flow (PBF) distribution after an Acid Aspiration event within this time frame has not been adequately studied. We determined therefore PBF pattern within the first hour after Acid Aspiration. METHODS Anesthetized, spontaneous breathing rats (n = 8) underwent unilateral endobronchial hydrochlorid Acid instillation so that the PBF distributions between the injured and non-injured lungs could be compared. The signal intensity of the lung parenchyma after injury was measured by magnetic resonance tomography. PBF distribution was determined by measuring the concentration of [68Ga]-radiolabeled microspheres using positron emission tomography. RESULTS Following Acid Aspiration, magnetic resonance images revealed increased signal intensity in the injured regions accompanied by reduced oxygenation. PBF was increased in all injured lungs (171 [150; 196], median [25%; 75%]) compared to the blood flow in all uninjured lungs (141 [122; 159], P = 0.0078). CONCLUSIONS From the first minute until fifty minutes after Acid-induced acute lung injury, the PBF was consistently increased in the injured lung. These blood flow elevation was accompanied by significant hypoxemia.
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Reduced pulmonary blood flow in regions of injury 2 hours after Acid Aspiration in rats
BMC Anesthesiology, 2015Co-Authors: Torsten Richter, Ralf Bergmann, Guido Musch, Jens Pietzsch, Thea KochAbstract:Background Aspiration-induced lung injury can decrease gas exchange and increase mortality. Acute lung injury following Acid Aspiration is characterized by elevated pulmonary blood flow (PBF) in damaged lung areas in the early inflammation stage. Knowledge of PBF patterns after Acid Aspiration is important for targeting intravenous treatments. We examined PBF in an experimental model at a later stage (2 hours after injury). Methods Anesthetized Wistar-Unilever rats (n = 5) underwent unilateral endobronchial instillation of hydrochloric Acid. The PBF distribution was compared between injured and uninjured sides and with that of untreated control animals (n = 6). Changes in lung density after injury were measured using computed tomography (CT). Regional PBF distribution was determined quantitatively in vivo 2 hours after Acid instillation by measuring the concentration of [^68Ga]-radiolabeled microspheres using positron emission tomography. Results CT scans revealed increased lung density in areas of Acid Aspiration. Lung injury was accompanied by impaired gas exchange. Acid Aspiration decreased the arterial pressure of oxygen from 157 mmHg [139;165] to 74 mmHg [67;86] at 20 minutes and tended toward restoration to 109 mmHg [69;114] at 110 minutes ( P
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reduced pulmonary blood flow in regions of injury 2 hours after Acid Aspiration in rats
BMC Anesthesiology, 2015Co-Authors: Torsten Richter, Ralf Bergmann, Guido Musch, Jens Pietzsch, Thea KochAbstract:Background: Aspiration-induced lung injury can decrease gas exchange and increase mortality. Acute lung injury following Acid Aspiration is characterized by elevated pulmonary blood flow (PBF) in damaged lung areas in the early inflammation stage. Knowledge of PBF patterns after Acid Aspiration is important for targeting intravenous treatments. We examined PBF in an experimental model at a later stage (2 hours after injury). Methods: Anesthetized Wistar-Unilever rats (n = 5) underwent unilateral endobronchial instillation of hydrochloric Acid. The PBF distribution was compared between injured and uninjured sides and with that of untreated control animals (n = 6). Changes in lung density after injury were measured using computed tomography (CT). Regional PBF distribution was determined quantitatively in vivo 2 hours after Acid instillation by measuring the concentration of [ 68 Ga]-radiolabeled microspheres using positron emission tomography. Results: CT scans revealed increased lung density in areas of Acid Aspiration. Lung injury was accompanied by impaired gas exchange. Acid Aspiration decreased the arterial pressure of oxygen from 157 mmHg [139;165] to 74 mmHg [67;86] at 20 minutes and tended toward restoration to 109 mmHg [69;114] at 110 minutes (P < 0.001). The PBF ratio of the middle region of the injured versus uninjured lungs of the Aspiration group (0.86 [0.7;0.9], median [25%;75%]) was significantly lower than the PBF ratio in the left versus right lung of the control group (1.02 [1.0;1.05]; P = 0.016). Conclusions: The PBF pattern 2 hours after Aspiration-induced lung injury showed a redistribution of PBF away from injured regions that was likely responsible for the partial recovery from hypoxemia over time. Treatments given intravenously 2 hours after Acid-induced lung injury may not preferentially reach the injured lung regions, contrary to what occurs during the first hour of inflammation.
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pulmonary blood flow increases in damaged regions directly after Acid Aspiration in rats
Anesthesiology, 2013Co-Authors: Torsten Richter, Ralf Bergmann, Jens Pietzsch, Lilla Knels, Frank Hofheinz, Michael Kasper, Martin Deile, M Ragaller, Thea KochAbstract:BACKGROUND: After gastric Aspiration events, patients are at risk of pulmonary dysfunction and the development of severe acute lung injury and acute respiratory distress syndrome, which may contribute to the development of an inflammatory reaction. The authors' aim in the current study was to investigate the role of the spatial distribution of pulmonary blood flow in the pathogenesis of pulmonary dysfunction during the early stages after Acid Aspiration. METHODS: The authors analyzed the pulmonary distribution of radiolabeled microspheres in normal (n = 6) and injured (n = 12) anesthetized rat lungs using positron emission tomography, computed tomography, and histological examination. RESULTS: Injured regions demonstrate increased pulmonary blood flow in association with reduced arterial pressure and the deterioration of arterial oxygenation. After Acid Aspiration, computed tomography scans revealed that lung density had increased in the injured regions and that these regions colocalized with areas of increased blood flow. The Acid was instilled into the middle and basal regions of the lungs. The blood flow was significantly increased to these regions compared with the blood flow to uninjured lungs in the control animals (middle region: 1.23 [1.1; 1.4] (median [25%; 75%]) vs. 1.04 [1.0; 1.1] and basal region: 1.25 [1.2; 1.3] vs. 1.02 [1.0; 1.05], respectively). The increase in blood flow did not seem to be due to vascular leakage into these injured areas. CONCLUSIONS: The data suggest that 10 min after Acid Aspiration, damaged areas are characterized by increased pulmonary blood flow. The results may impact further treatment strategies, such as drug targeting.