University of Wisconsin solution for pulmonary preservation in a rat transplant model

Aeba, Ryo; Keenan, Robert J.; Hardesty, Robert L.; Yousem, Samuel A.; Hamamoto, Isao; Griffith, Bartley P.

doi:10.1016/0003-4975(92)91325-4

Cited by 49 publications

(22 citation statements)

References 21 publications

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“…Compounds such as diphenylphenylenediamine (DPPD) (31), the lazaroids (38)(39)(40), have been in use as antioxidants to prevent the oxidation of LDL. Demethylation of amines is a characteristic oxidation reaction (49,50) and in vivo, such reactions characterize detoxification reactions.…”

Section: Resultsmentioning

confidence: 99%

Antioxidant: a new role for RU-486 and related compounds.

Parthasarathy¹,

Morales²,

Murphy³

1994

J. Clin. Invest.

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RU-486 (17 f8-hydroxy 4-dimethylaminophenyl-17-a-propenyl estrone 4,9 diene-3-one; mifepristone) is suggested to act by binding to progesterone and glucocorticoid receptors. Based on its chemical nature, we anticipated that RU-486 may have potent antioxidant properties. We used the oxidation of LDL as our model system. RU-486 and a similar compound, onapristone, at 1-5-IuM concentrations, decreased the formation of oxidized LDL. LDL isolated from plasma of subjects who were orally supplemented with RU-486 was resistant to oxidation, as compared to LDL isolated from control plasma.The antioxidant effect of RU-486 appears to reside in the dimethylaminophenyl side chain moiety. Reduction of the A-ring of the steroid molecule had no effect on its antioxidant property. Analogs of RU-486 which lack the dimethylaminophenyl group, were without antioxidant activity. Levoniorgestrel, which

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Section: Resultsmentioning

confidence: 99%

Antioxidant: a new role for RU-486 and related compounds.

Parthasarathy¹,

Morales²,

Murphy³

1994

J. Clin. Invest.

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“…In an established rabbit model, lazaroid U75412E attenuated chemical mediators after smoke insult (34,35). These studies suggest that lazaroids may exert their protective action not only by a direct antioxidant activity (1,19,29,30) and inhibition of lipid peroxidation (17) but also by suppressing the expression and/or release of cytokines (28), such as interleukin-8 (22) and tumor necrosis factor-a (TNF-a) (35). This study provides further evidence that U75412E can protect against respiratory epithelial damage and gas exchange impairment caused by smoke.…”

Section: Introductionmentioning

confidence: 79%

Early Alterations of Lung Injury Following Acute Smoke Exposure and 21-Aminosteroid Treatment

et al. 1999

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In a simulated fire-related smoke exposure protocol, New Zealand white rabbits were utilized to investigate the potential effects of the 21-aminosteroid (lazaroid) analog U75412E on the early events of acute lung injury. Inhalation of a total of 1.6 mg/kg U75412E aerosolized at a rate of 1.53 mg/min at 0.5 hr after smoke exposure significantly attenuated the extent of lung injury at 1 hr, as evidenced by decreased bronchoalveolar lavage (BAL) concentration of total protein, 6-keto-prostaglandin F 1 -α, and blood gas defect. Histopathologic examination demonstrated that the lazaroid significantly attenuated smoke-induced lung injury as evidenced by a decrease in wet lung/body weight ratio, necrosis, and sloughing of airway epithelial cells. Electron microscopy showed that the lazaroid decreased smoke-induced interstitial edema and the vacuolization of alveolar type II epithelium (21.6 ± 9.7 vs 8.5 ± 3.6 vacuoled blebs/cell, smoke only vs smoke + lazaroid). However, U75412E did not attenuate smoke-induced changes in BAL concentration of tumor necrosis factor-α, total cell count, and granulocyte percentage. These observations suggest that U75412E may exert its action through cooperative mechanisms, such as the modulation of arachidonic acid metabolism, in addition to its characterized antioxidative effects.

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“…In addition, researchers are under increasing pressure from government animal welfare departments to use small animals in models. Some rodent models have been applied to studies of lung storage, but they are technically demanding, particularly those involving allotransplantation (Corris et al 1987, Aeba et al 1992. Allotransplantation requires bronchial and vascular anastomoses, each of which may introduce variability when considering the results of reper£Usion.…”

Section: Resultsmentioning

confidence: 99%

“…Although small-animal models have been developed to address certain aspects of lung preservation, all have had limitations which restrict their usefulness. For instance, models requiring rat or rabbit lung transplantation demand a high level of expertise, the required skills take a considerable time to acquire [Aeba 1992), and accurate quantitative data of pulmonary function can be difficult to obtain (adorn 1987). Large animal transplant models are, in addition, timeconsuming and expensive.…”

mentioning

confidence: 99%

A technique for studying the function of an isolated, perfused and ventilated lung in a rat model

et al. 1995

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SummaryWe describe a technique which allows perfusion of an isolated, ventilated rat lung with an extracorporeal veno-venous circuit from a support animal. This model provides stable and reliable function of the isolated lung for up to 3 h, thus overcoming some of the disadvantages of previous models. It may prove a potentially useful model for assessing ischaemic lung injury. Keywords Lungj preservationj modelOne factor that has impeded progress in lung preservation for transplantation is the lack of a reliable, simple, and inexpensive animal model for evaluating the effectiveness of graft storage techniques. Although small-animal models have been developed to address certain aspects of lung preservation, all have had limitations which restrict their usefulness. For instance, models requiring rat or rabbit lung transplantation demand a high level of expertise, the required skills take a considerable time to acquire [Aeba 1992), and accurate quantitative data of pulmonary function can be difficult to obtain (adorn 1987). Large animal transplant models are, in addition, timeconsuming and expensive. Isolated, perfused lung models have been described in the rat and rabbit but these have lacked either the capacity to assess pulmonary gas exchange (Breda et al. 1985), or have allowed only very brief periods of perfusion

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University of Wisconsin solution for pulmonary preservation in a rat transplant model

Cited by 49 publications

References 21 publications

Antioxidant: a new role for RU-486 and related compounds.

Antioxidant: a new role for RU-486 and related compounds.

Early Alterations of Lung Injury Following Acute Smoke Exposure and 21-Aminosteroid Treatment

A technique for studying the function of an isolated, perfused and ventilated lung in a rat model

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