Experimental pulmonary emphysema induced in the rat by intratracheally administered elastase: Morphogenesis

Busch, R. H.; Lauhala, K.E.; Loscutoff, S.M.; McDonald, K.E.

doi:10.1016/0013-9351(84)90044-6

Cited by 43 publications

(22 citation statements)

References 3 publications

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“…The attractiveness of this model is that a single hit, the instillation of a bolus of an elastolytic proteinase, such as porcine pancreatic or human neutrophil elastase, results in the loss of alveolar walls, as judged by stereology [24], whereas nonelastolytic proteinases failed to induce emphysematous lesions [28]. However, the desired effect of elastase is frequently limited to a narrow window of dosage, below which no significant loss of alveoli is observed, whereas a higher dose may result in severe pulmonary haemorrhage and high mortality [29,30].…”

Section: Elastase Instillation Models Of Emphysemamentioning

confidence: 99%

Animal models of pulmonary emphysema: a stereologist's perspective

Fehrenbach¹

2006

Eur Respir Rev

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A variety of animal models have been suggested as models of pulmonary emphysema; these are critically discussed in the present article from a stereologist's perspective. In addition, a stereological design for the quantification of experimentally induced emphysema is proposed.On the basis of the widely accepted definition of pulmonary emphysema being an ''abnormal permanent enlargement of the airspaces distal to the terminal bronchioles, accompanied by destruction of their walls,'' quantitative morphology is the only method with which to reliably assess the presence of emphysema. Recognising this, careful inspection of animal models that are based on instillation of elastase, genetic alterations, inhalation of cigarette smoke or induction of apoptosis, reveals that both criteria of emphysema definition were demonstrated in surprisingly few of them.Several aspects are suggested to be critical for the understanding of animal models of human emphysema. For example, genetic models that rely on the inhibition of the formation of alveoli during post-natal alveolarisation should clearly be distinguished from models that rely on the loss of mature alveoli after alveolarisation is complete. Furthermore, inhalation models that are characterised by exposed animals exhibiting a severe loss of body weight should carefully examine the relative contribution of intervention and weight loss, respectively. Models that rely on the exposure of juvenile animals for several weeks or even months should take into account the effects of normal lung growth and ageing.Stereology offers appropriate tools with which to quantify the parameters relevant to assess development and the regeneration of emphysema. Stereologists continue to develop tools that will help ascertain the reliability of established and new models. If inappropriate parameters continue to be used for the evaluation of animal models of emphysema, thinking and resources are likely to be misdirected and the models may limit rather than expand the understanding of human emphysema and the development of new therapies.

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Section: Elastase Instillation Models Of Emphysemamentioning

confidence: 99%

Animal models of pulmonary emphysema: a stereologist's perspective

Fehrenbach¹

2006

Eur Respir Rev

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“…The hamster has been the most common rodent emphysema model because of its innate sensitivity to elastolytic enzymes (60,73). The rat, mouse, and rabbit also have been used as models despite their lower sensitivity to elastase (60,(74)(75)(76). Most studies use porcine pancreatic or human neutrophil elastase (72,73) to induce disease, although early models (72) used an unpurified cocktail of vegetable enzymes (papain).…”

Section: Rodent Models Of Cardiopulmonary Diseases Pulmonary Diseasesmentioning

confidence: 99%

“…Immediately after intratracheal instillation of elastase, degradation of elastin, rupture of the alveolar epithelium, pulmonary edema, hemorrhage, and modest infiltration of neutrophils occur, with airspace enlargement noted within hours of the treatment (61,72,76). Synthesis of new elastin and repair begin almost immediately and normal total lung elastin and collagen levels are restored in 3 to 4 weeks; however, distortion and derangement of alveolar structure is progressive through this period and these changes are largely permanent.…”

Section: Rodent Models Of Cardiopulmonary Diseases Pulmonary Diseasesmentioning

confidence: 99%

Rodent Models of Cardiopulmonary Disease: Their Potential Applicability in Studies of Air Pollutant Susceptibility

Kodavanti¹,

Costa²,

Bromberg³

1998

Environmental Health Perspectives

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The mechanisms by which increased mortality and morbidity occur in individuals with preexistent cardiopulmonary disease following acute episodes of air pollution are unknown. Studies involving air pollution effects on animal models of human cardiopulmonary diseases are both infrequent and difficult to interpret. Such models are, however, extensively used in studies of disease pathogenesis. Primarily they comprise those developed by genetic, pharmacologic, or surgical manipulations of the cardiopulmonary system. This review attempts a comprehensive description of rodent cardiopulmonary disease models in the context of their potential application to susceptibility studies of air pollutants regardless of whether the models have been previously used for such studies. The pulmonary disease models include bronchitis, emphysema, asthma/allergy, chronic obstructive pulmonary disease, interstitial fibrosis, and infection. The models of systemic hypertension and congestive heart failure include: those derived by genetics (spontaneously hypertensive, Dahl S, renin transgenic, and other rodent models); congestive heart failure models derived by surgical manipulations; viral myocarditis; and cardiomyopathy induced by adriamycin. The characteristic pathogenic features critical to understanding the susceptibility to inhaled toxicants are described. It is anticipated that this review will provide a ready reference for the selection of appropriate rodent models of cardiopulmonary diseases and identify not only their pathobiologic similarities and/or differences to humans but also their potential usefulness in susceptibility studies.

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“…), but collagen fibers are fragmented (Bush et al 1984). With 10 U of elastase per 100 g of body weight lung elastin is decreased (Fonzi and Lungarella 1980), however, with 25 U elastin is initially decreased and later normalized ) and with 35 U this protein is increased (Valentine et al 1983).…”

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confidence: 96%

Dose dependency of intratracheal elastase-induced changes in pressure volume curve and morphometry in rat lungs.

Sato

Kato

Takahashi

et al. 1990

Tohoku J. Exp. Med.

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We studied the dose-dependency of the lung pressure-volume curve (n -37) and morphometry (n -30) with intratracheally administered elastase. Four weeks after elastase was instilled at dosages of 20 (EL-20), 40, 80, and 100 U/100 g wt., chord compliance between 50 and 70% of total lung capacity (TLC) (C5o-70) and that between 80 and 100% TLC (C8o-100) Were measured. After a significant initial reduction, the weight of the EL-80 group recovered to the control level, whereas the weight curve of the EL-100 significantly decreased below that of the EL-80. Lung volumes of all the elastase-treated groups were significantly larger than those of control. Air-filled lung volumes monotonously increased when the elastase dose was increased from 20 to 80 U/100 g wt. In contrast lung volume of the EL-100 was significantly lower than that of the EL-80. On the other hand, liquid-filled lung volumes monotonously increased from 20 to 100 U/100 g wt. Cao-ioo was significantly smaller in the EL-100 than in the EL-80. The mean linear intercept increased and alveolar surface area decreased monotonously over the dose range tested. We conclude that there is a critical dose of elastase below which lung volume is increased and above which the increase is suppressed when elastase is administered intratracheally to Wistar rats. pulmonary emphysema ; mean linear intercept ; lung compliance ; alveolar surface area

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Experimental pulmonary emphysema induced in the rat by intratracheally administered elastase: Morphogenesis

Cited by 43 publications

References 3 publications

Animal models of pulmonary emphysema: a stereologist's perspective

Animal models of pulmonary emphysema: a stereologist's perspective

Rodent Models of Cardiopulmonary Disease: Their Potential Applicability in Studies of Air Pollutant Susceptibility

Dose dependency of intratracheal elastase-induced changes in pressure volume curve and morphometry in rat lungs.

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