Preparation of chronic lung lymph fistulas in sheep

Staub, Norman C.; Bland, Richard D.; Brigham, Kenneth L.; Demling, Robert H.; Erdmann, A. John; Woolverton, William C.

doi:10.1016/0022-4804(75)90056-6

Cited by 360 publications

(132 citation statements)

References 7 publications

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“…Experiments are currently being performed in our laboratory on the use of ascorbic acid to prevent the endotoxin-induced pulmonary dysfunction in the sheep model according to Staub et al (13).…”

Section: Discussionmentioning

confidence: 99%

Effect of Ascorbic Acid on Neutrophil Functions and Hypoxanthine/Xanthine Oxidase-Generated, Oxygen-Derived Radicals

Dwenger

Funck²,

Lueken³

et al. 1992

Clinical Chemistry and Laboratory Medicine

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Summary:The effect of ascorbic acid on neutrophil functions was investigated.The chemiluminescence of isolated neutrophils, stimulated with N-fonnyl-L-methionyl-L-leucyl-L-phenylalanine, latex, lipopolysaccharide from Escherichia coli, zymosan A, or 4 -phorbol 12 -myristate 13a-acetate was inhibited up to 99% by the dose-dependent oxygen radical scavenging activity of 6 mmol/1 ascorbic acid. The chemiluminescence of neutrophils in blood, stimulated with 4 -phorbol 12 -myristate 13a-acetate, or with zymosan A was inhibited 35% or 48%, respectively, by 6 mmol/1 ascorbic acid.Ascorbic acid, up to 6 mmol/1, did not inhibit the release of -N-acetylglucosaminidase and elastase from isolated neutrophils activated by the above stimulatory agents.During neutrophil/nylon fibre interaction ascorbic acid reduced the oxygen radical production dose-dependently (77% inhibition of the chemiluminescence response at 6 mmol/1 ascorbic acid), whereas the adherence was unaffected. Hypoxanthine/xanthine oxidase-generated oxygen radicals were scavenged by ascorbic acid in a dose-dependent manner (99% inhibition of the chemiluminescence response at 100 μιηοΐ/ΐ ascorbic acid).From these results, ascorbic acid can highly be recommended for animal experiments and clinical studies in patients with trauma, shock and sepsis and for studies to prevent or reduce reperfusion injuries.

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Section: Discussionmentioning

confidence: 99%

Effect of Ascorbic Acid on Neutrophil Functions and Hypoxanthine/Xanthine Oxidase-Generated, Oxygen-Derived Radicals

Dwenger

Funck²,

Lueken³

et al. 1992

Clinical Chemistry and Laboratory Medicine

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“…The caudal mediastinal lymph node was cannulated (Silastic medial grade tubing, 0.025 in. ID, 0.047 in, OD, Dow Corning; Midland, MI) according to a modification of the technique described by Staub and colleagues (22). The contribution to the node was removed by ligation of the tail of the caudal mediastinal lymph node and cauterization of the systemic diaphragmatic lymph vessels (20).…”

Section: Surgical Preparation and Injurymentioning

confidence: 99%

Burn and smoke inhalation injury in sheep depletes vitamin E: Kinetic studies using deuterated tocopherols

Traber

Shimoda

Murakami

et al. 2007

Free Radical Biology and Medicine

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To test the hypothesis that burn and smoke injury will deplete tissue α-tocopherol and cause its faster plasma disappearance, deuterium-labeled vitamin E was administered to sheep exposed to both surface skin burn and smoke insufflation that causes injury similar to human victims of fire accidents. Two different protocols were used: 1) deuterated vitamin E was administered orally with food at 0 time (just prior to injury), or 2) the labeled vitamin E was administered orally with food the day prior to injury. The animals that had been operatively prepared seven days before, were anaesthetized, then received both 40% body surface area 3rd° burn and 48 breaths of cotton smoke, or sham injuries. All were resuscitated with Ringer's lactate solution (4 ml/kg/% BSA burn/24h) and mechanically ventilated. Blood samples were collected at various times after vitamin E dosing. In both studies the depletion of plasma α-tocopherol was faster in the injured sheep. The sheep given deuterated vitamin E 24 h prior to injury had similar maximum α-tocopherol concentrations at similar times. The exponential rates of α -tocopherol disappearance were 1.5 times greater and half-lives were 12 h shorter (p<0.05) in the injured sheep. In separate studies, various tissues were obtained from sheep that were sacrificed from 4 h to 48 h after injury. The liver α -tocopherol concentrations in sheep killed at various times after injury appear to show a linear decrease at a rate of 0.1 nmol α -tocopherol/ g liver per hour, suggesting that the liver is supplying α -tocopherol to maintain the plasma and lung α -tocopherol concentrations, but that this injury is so severe that the liver is unable to maintain lung α -tocopherol concentrations. These findings suggest that α -tocopherol should be administered to burn patients to prevent vitamin E depletion and to protect against oxidative stress from burn injury.

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“…Anesthesia was maintained with 1.0-1.5% fluothane, 50% nitrous oxide, and 50% oxygen. Lung lymph was collected from the caudal efferent lymphatic duct cannulated with a heparinized silastic catheter by the technique of Staub et al (28). Bronchoalveolar lavage fluid was obtained by lavage through a fiberoptic bronchoscope (Olympus) using a single 50-ml aliquot of normal saline.…”

Section: Methodsmentioning

confidence: 99%

Fate of aerosolized recombinant DNA-produced alpha 1-antitrypsin: use of the epithelial surface of the lower respiratory tract to administer proteins of therapeutic importance.

Hubbard

Casolaro

Mitchell

et al. 1989

Proc. Natl. Acad. Sci. U.S.A.

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To evaluate the possibility of administering therapeutic proteins via the respiratory route, we administered an aerosol ofrecombinant DNA-produced human a1-antitrypsin (rAAT) to anesthetized sheep and measured levels of the protein in epithelial lining fluid (ELF), lung lymph, blood, and urine.Using a nebulizer that generated aerosol droplets with a mass median aerodynamic diameter of 2.7 psm (55% of droplets were <3 ,Am, a particle size optimal for deposition on the alveolar epithelium), in vitro studies demonstrated that the aerosolized rAAT remained intact and fully functional as an inhibitor of neutrophil elastase. When aerosolized to sheep, the 45-kDa rAAT molecule diused across the alveolar epithelium, as evidenced by its presence in lung lymph and in blood. Comparison ofELF, lymph, blood, and urine rAAT levels demonstrated that the process was concentration dependent, with highest levels in ELF and in descending concentrations with 410-fold concentration differences in each consecutive compartment, respectively. Importantly (6,7), and studies with recombinant interferon-'y, interferon-a, and granulocytemonocyte colony-stimulating factor, erythropoietin, and interleukin 2 have necessitated subcutaneous, intramuscular, or intravenous routes of administration (1-5, 9, 10).As an alternative approach to administration ofrecombinant proteins (and proteins in general, independent of the source), the present study was designed to capitalize on the enormous surface area of the lung as a potential absorptive surface through which proteins of therapeutic importance could gain access to the interstitium of the lung and plasma while remaining intact. This concept is based on the knowledge that (i) droplets of 3-,um diameter inhaled as an aerosol have the potential to reach the alveolar surface (11-14); (ii) the epithelial surface of the human lower respiratory tract is very large, typically 140 m2 in adults (15); (iii) plasma proteins as large as 100 kDa are found in the epithelial lining fluid surface of the lung, suggesting that proteins can diffuse across the capillary endothelium, the alveolar interstitium, and the alveolar epithelium (16)(17)(18)(19); and (iv) although there are no quantitative data available relating to the measurement of autologous natural or recombinant proteins from lower respiratory tract epithelial lining fluid to plasma, it is known that when solutions of heterologous proteins are instilled in the trachea of experimental animals, the protein can be subsequently detected in the pulmonary interstitium and blood (20)(21)(22).As a model to evaluate the possibility of using the lower respiratory tract to administer proteins of therapeutic interest, we have examined the pulmonary absorption of an aerosol of yeast-produced human recombinant a1-antitrypsin (rAAT), a 45-kDa single-chain polypeptide that functions as an inhibitor of neutrophil elastase (23). To evaluate the absorption of the molecule, we have used sheep, an experimental animal in which the pulmonary lymphatics can be sample...

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Preparation of chronic lung lymph fistulas in sheep

Cited by 360 publications

References 7 publications

Effect of Ascorbic Acid on Neutrophil Functions and Hypoxanthine/Xanthine Oxidase-Generated, Oxygen-Derived Radicals

Effect of Ascorbic Acid on Neutrophil Functions and Hypoxanthine/Xanthine Oxidase-Generated, Oxygen-Derived Radicals

Burn and smoke inhalation injury in sheep depletes vitamin E: Kinetic studies using deuterated tocopherols

Fate of aerosolized recombinant DNA-produced alpha 1-antitrypsin: use of the epithelial surface of the lower respiratory tract to administer proteins of therapeutic importance.

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