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. 1984 Jun;56:11–22. doi: 10.1289/ehp.845611

Pulmonary function testing in small laboratory mammals.

J J O'Neil, J A Raub
PMCID: PMC1568219  PMID: 6434299

Abstract

The lung is the primary organ likely to be exposed by inhalation studies and, therefore, measurement of changes in lung function are of particular interest to the pulmonary physiologist and toxicologist. Tests of pulmonary function have been developed which can be used with small animals to measure spirometry (lung volumes), mechanics, distribution of ventilation, gas exchange or control of ventilation. These tests were designed on the basis of similar tests which are used in humans to diagnose and manage patients with lung disease. A major difference is that many of the measurements are performed in anesthetized animals, while human pulmonary function is usually measured in awake cooperating individuals. In addition, the measurement of respiratory events in small animals requires sensitive and rapidly responding equipment, because signals may be small and events can occur quickly. In general, the measurements described provide information on the change in normal lung function which results primarily from structural changes. These tests of pulmonary function can be repetitively and routinely accomplished and the results appear to be highly reproducible. Although some are quite sophisticated, many can be undertaken with relatively inexpensive equipment and provide useful information for toxicological testing.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Agostoni E., D'Angelo E. Comparative features of the transpulmonary pressure. Respir Physiol. 1970;11(1):76–83. doi: 10.1016/0034-5687(70)90103-9. [DOI] [PubMed] [Google Scholar]
  2. CHAPIN J. L. Ventilatory response of the unrestrained and unanesthetized hamster to CO2. Am J Physiol. 1954 Oct;179(1):146–148. doi: 10.1152/ajplegacy.1954.179.1.146. [DOI] [PubMed] [Google Scholar]
  3. Castile R. G., Hyatt R. E., Rodarte J. R. Determinants of maximal expiratory flow and density dependence in normal humans. J Appl Physiol Respir Environ Exerc Physiol. 1980 Nov;49(5):897–904. doi: 10.1152/jappl.1980.49.5.897. [DOI] [PubMed] [Google Scholar]
  4. Chenoweth M. B. Inhalation anesthetics. Fed Proc. 1978 Sep;37(11):2501–2503. [PubMed] [Google Scholar]
  5. Chválová M., Kuncová M., Havránková J., Palecek F. Regulation of respiration in experimental silicosis. Physiol Bohemoslov. 1974;23(6):539–547. [PubMed] [Google Scholar]
  6. DRORBAUGH J. E., FENN W. O. A barometric method for measuring ventilation in newborn infants. Pediatrics. 1955 Jul;16(1):81–87. [PubMed] [Google Scholar]
  7. Damon E. G., Mauderly J. L., Jones R. K. Early effects of intratracheal Instillation of elastase on mortality, Respiratory function, and pulmonary morphometry of F-344 rats. Toxicol Appl Pharmacol. 1982 Jul;64(3):465–475. doi: 10.1016/0041-008x(82)90243-5. [DOI] [PubMed] [Google Scholar]
  8. Diamond L., O'Donnell M. Pulmonary mechanics in normal rats. J Appl Physiol Respir Environ Exerc Physiol. 1977 Dec;43(6):942–948. doi: 10.1152/jappl.1977.43.6.942. [DOI] [PubMed] [Google Scholar]
  9. Epstein M. A., Epstein R. A. A theoretical analysis of the barometric method for measurement of tidal volume. Respir Physiol. 1978 Jan;32(1):105–120. doi: 10.1016/0034-5687(78)90103-2. [DOI] [PubMed] [Google Scholar]
  10. FRY D. L. Physiologic recording by modern instruments with particular reference to pressure recording. Physiol Rev. 1960 Oct;40:753–788. doi: 10.1152/physrev.1960.40.4.753. [DOI] [PubMed] [Google Scholar]
  11. Finucane K. E., Egan B. A., Dawson S. V. Linearity and frequency response of pneumotachographs. J Appl Physiol. 1972 Jan;32(1):121–126. doi: 10.1152/jappl.1972.32.1.121. [DOI] [PubMed] [Google Scholar]
  12. Fleming G. M., Chester E. H., Saniie J., Saidel G. M. Ventilation inhomogeneity using multibreath nitrogen washout: comparison of moment ratios and other indexes. Am Rev Respir Dis. 1980 May;121(5):789–794. doi: 10.1164/arrd.1980.121.5.789. [DOI] [PubMed] [Google Scholar]
  13. Frazer D. G., Weber K. C. Trapped air in ventilated excised rat lungs. J Appl Physiol. 1976 Jun;40(6):915–922. doi: 10.1152/jappl.1976.40.6.915. [DOI] [PubMed] [Google Scholar]
  14. Frazer D. G., Weber K. C. Trapped gas at maximum lung volume in intact isolated rat lungs. Respir Physiol. 1979 Jul;37(2):173–184. doi: 10.1016/0034-5687(79)90069-0. [DOI] [PubMed] [Google Scholar]
  15. Freeman G., Crane S. C., Furiosi N. J., Stephens R. J., Evans M. J., Moore W. D. Covert reduction in ventilatory surface in rats during prolonged exposure to subacute nitrogen dioxide. Am Rev Respir Dis. 1972 Oct;106(4):563–579. doi: 10.1164/arrd.1972.106.4.563. [DOI] [PubMed] [Google Scholar]
  16. Gillespie J. R., Bruce E., Alexander J., Mead J. Breathing responses of unanesthetized man and guinea pigs to increased transrespiratory pressure. J Appl Physiol Respir Environ Exerc Physiol. 1979 Jul;47(1):119–125. doi: 10.1152/jappl.1979.47.1.119. [DOI] [PubMed] [Google Scholar]
  17. Hayatdavoudi G., O'Neil J. J., Barry B. E., Freeman B. A., Crapo J. D. Pulmonary injury in rats following continuous exposure to 60% O2 for 7 days. J Appl Physiol Respir Environ Exerc Physiol. 1981 Nov;51(5):1220–1231. doi: 10.1152/jappl.1981.51.5.1220. [DOI] [PubMed] [Google Scholar]
  18. Holub D., Frank R. A system for rapid measurement of lung function in small animals. J Appl Physiol Respir Environ Exerc Physiol. 1979 Feb;46(2):394–398. doi: 10.1152/jappl.1979.46.2.394. [DOI] [PubMed] [Google Scholar]
  19. Hök B. Dynamic calibration of manometer systems. Med Biol Eng. 1976 Mar;14(2):193–198. doi: 10.1007/BF02478747. [DOI] [PubMed] [Google Scholar]
  20. Jackson A. C., Vinegar A. A technique for measuring frequency response of pressure, volume, and flow transducers. J Appl Physiol Respir Environ Exerc Physiol. 1979 Aug;47(2):462–467. doi: 10.1152/jappl.1979.47.2.462. [DOI] [PubMed] [Google Scholar]
  21. Jackson A. C., Watson J. W. Oscillatory mechanics of the respiratory system in normal rats. Respir Physiol. 1982 Jun;48(3):309–322. doi: 10.1016/0034-5687(82)90036-6. [DOI] [PubMed] [Google Scholar]
  22. Jacky J. P. A plethysmograph for long-term measurements of ventilation in unrestrained animals. J Appl Physiol Respir Environ Exerc Physiol. 1978 Oct;45(4):644–647. doi: 10.1152/jappl.1978.45.4.644. [DOI] [PubMed] [Google Scholar]
  23. Jacky J. P. Barometric measurement of tidal volume: effects of pattern and nasal temperature. J Appl Physiol Respir Environ Exerc Physiol. 1980 Aug;49(2):319–325. doi: 10.1152/jappl.1980.49.2.319. [DOI] [PubMed] [Google Scholar]
  24. Johanson W. G., Jr, Pierce A. K. Lung structure and function with age in normal rats and rats with papain emphysema. J Clin Invest. 1973 Nov;52(11):2921–2927. doi: 10.1172/JCI107488. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Kao D. K., Tierney D. F. Air embolism with positive-pressure ventilation of rats. J Appl Physiol Respir Environ Exerc Physiol. 1977 Mar;42(3):368–371. doi: 10.1152/jappl.1977.42.3.368. [DOI] [PubMed] [Google Scholar]
  26. King T. K. Measurement of functional residual capacity in the rat. J Appl Physiol. 1966 Jan;21(1):233–236. doi: 10.1152/jappl.1966.21.1.233. [DOI] [PubMed] [Google Scholar]
  27. Koo K. W., Leith D. E., Sherter C. B., Snider G. L. Respiratory mechanics in normal hamsters. J Appl Physiol. 1976 Jun;40(6):936–942. doi: 10.1152/jappl.1976.40.6.936. [DOI] [PubMed] [Google Scholar]
  28. Lai Y. L., Hildebrandt J. Respiratory mechanics in the anesthetized rat. J Appl Physiol Respir Environ Exerc Physiol. 1978 Aug;45(2):255–260. doi: 10.1152/jappl.1978.45.2.255. [DOI] [PubMed] [Google Scholar]
  29. Lai Y. L., Lamm J. E., Hildebrandt J. Ventilation during prolonged hypercapnia in the rat. J Appl Physiol Respir Environ Exerc Physiol. 1981 Jul;51(1):78–83. doi: 10.1152/jappl.1981.51.1.78. [DOI] [PubMed] [Google Scholar]
  30. Lai Y. L. Lung volume and pleural pressure in the anesthetized hamster. J Appl Physiol Respir Environ Exerc Physiol. 1979 May;46(5):927–931. doi: 10.1152/jappl.1979.46.5.927. [DOI] [PubMed] [Google Scholar]
  31. Lai Y. L., Tsuya Y., Hildebrandt J. Ventilatory responses to acute CO2 exposure in the rat. J Appl Physiol Respir Environ Exerc Physiol. 1978 Oct;45(4):611–618. doi: 10.1152/jappl.1978.45.4.611. [DOI] [PubMed] [Google Scholar]
  32. Leith D. E. Comparative mammalian respiratory mechanics. Physiologist. 1976 Nov;19(4):485–510. [PubMed] [Google Scholar]
  33. Likens S. A., Mauderly J. L. Effect of elastase or histamine on single-breath N2 washouts in the rat. J Appl Physiol Respir Environ Exerc Physiol. 1982 Jan;52(1):141–146. doi: 10.1152/jappl.1982.52.1.141. [DOI] [PubMed] [Google Scholar]
  34. Lucey E. C., Celli B. R., Snider G. L. Maximum expiratory flow and transpulmonary pressure in the hamster. J Appl Physiol Respir Environ Exerc Physiol. 1978 Dec;45(6):840–845. doi: 10.1152/jappl.1978.45.6.840. [DOI] [PubMed] [Google Scholar]
  35. Lucey E. C., O'Brien J. J., Jr, Pereira W., Jr, Snider G. L. Arterial blood gas values in emphysematous hamsters. Am Rev Respir Dis. 1980 Jan;121(1):83–89. doi: 10.1164/arrd.1980.121.1.83. [DOI] [PubMed] [Google Scholar]
  36. Malan A. Ventilation measured by body plethysmography in hibernating mammals and in poikilotherms. Respir Physiol. 1973 Jan;17(1):32–44. doi: 10.1016/0034-5687(73)90108-4. [DOI] [PubMed] [Google Scholar]
  37. Mead J. Analysis of the configuration of maximum expiratory flow-volume curves. J Appl Physiol Respir Environ Exerc Physiol. 1978 Feb;44(2):156–165. doi: 10.1152/jappl.1978.44.2.156. [DOI] [PubMed] [Google Scholar]
  38. Meadows J. A., 3rd, Rodarte J. R., Hyatt R. E. Density dependence of maximal expiratory flow in chronic obstructive pulmonary disease. Am Rev Respir Dis. 1980 Jan;121(1):47–53. doi: 10.1164/arrd.1980.121.1.47. [DOI] [PubMed] [Google Scholar]
  39. O'Brien J. J., Jr, Lucey E. C., Snider G. L. Arterial blood gases in normal hamsters at rest and during exercise. J Appl Physiol Respir Environ Exerc Physiol. 1979 Apr;46(4):806–810. doi: 10.1152/jappl.1979.46.4.806. [DOI] [PubMed] [Google Scholar]
  40. Palecek F. Measurement of ventilatory mechanics in the rat. J Appl Physiol. 1969 Jul;27(1):149–156. doi: 10.1152/jappl.1969.27.1.149. [DOI] [PubMed] [Google Scholar]
  41. Pappenheimer J. R. Sleep and respiration of rats during hypoxia. J Physiol. 1977 Mar;266(1):191–207. doi: 10.1113/jphysiol.1977.sp011763. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Proulx P. A., Harf A., Lorino H., Atlan G., Laurent D. Dynamic characteristics of air-filled differential pressure transducers. J Appl Physiol Respir Environ Exerc Physiol. 1979 Mar;46(3):608–614. doi: 10.1152/jappl.1979.46.3.608. [DOI] [PubMed] [Google Scholar]
  43. Raub J. A., Mercer R. R., Miller F. J., Graham J. A., O'Neil J. J. Dose response of elastase-induced emphysema in hamsters. Am Rev Respir Dis. 1982 Apr;125(4):432–435. doi: 10.1164/arrd.1982.125.4.432. [DOI] [PubMed] [Google Scholar]
  44. Saidel G. M., Salmon R. B., Chester E. H. Moment analysis of multibreath lung washout. J Appl Physiol. 1975 Feb;38(2):328–334. doi: 10.1152/jappl.1975.38.2.328. [DOI] [PubMed] [Google Scholar]
  45. Seeherman H. J., Taylor C. R., Maloiy G. M., Armstrong R. B. Design of the mammalian respiratory system. II. Measuring maximum aerobic capacity. Respir Physiol. 1981 Apr;44(1):11–23. doi: 10.1016/0034-5687(81)90074-8. [DOI] [PubMed] [Google Scholar]
  46. Sinnett E. E., Jackson A. C., Leith D. E., Butler J. P. Fast integrated flow plethysmograph for small mammals. J Appl Physiol Respir Environ Exerc Physiol. 1981 May;50(5):1104–1110. doi: 10.1152/jappl.1981.50.5.1104. [DOI] [PubMed] [Google Scholar]
  47. Snider G. L., Celli B. R., Goldstein R. H., O'Brien J. J., Lucey E. C. Chronic interstitial pulmonary fibrosis produced in hamsters by endotracheal bleomycin. Lung volumes, volume-pressure relations, carbon monoxide uptake, and arterial blood gas studied. Am Rev Respir Dis. 1978 Feb;117(2):289–297. doi: 10.1164/arrd.1978.117.2.289. [DOI] [PubMed] [Google Scholar]
  48. Snider G. L., Sherter C. B., Koo K. W., Karlinsky J. B., Hayes J. A., Franzblau C. Respiratory mechanics in hamsters following treatment with endotracrael elastase or collagenase. J Appl Physiol Respir Environ Exerc Physiol. 1977 Feb;42(2):206–215. doi: 10.1152/jappl.1977.42.2.206. [DOI] [PubMed] [Google Scholar]
  49. Spells K. E. Comparative studies in lung mechanics based on a survey of literature data. Respir Physiol. 1969 Dec;8(1):37–57. doi: 10.1016/0034-5687(69)90043-7. [DOI] [PubMed] [Google Scholar]
  50. Stahl W. R. Scaling of respiratory variables in mammals. J Appl Physiol. 1967 Mar;22(3):453–460. doi: 10.1152/jappl.1967.22.3.453. [DOI] [PubMed] [Google Scholar]
  51. Stengel P. W., Frazer D. G., Weber K. C. Lung degassing: an evaluation of two methods. J Appl Physiol Respir Environ Exerc Physiol. 1980 Feb;48(2):370–375. doi: 10.1152/jappl.1980.48.2.370. [DOI] [PubMed] [Google Scholar]
  52. TENNEY S. M., REMMERS J. E. Comparative quantitative morphology of the mammalian lung: diffusing area. Nature. 1963 Jan 5;197:54–56. doi: 10.1038/197054a0. [DOI] [PubMed] [Google Scholar]
  53. Takezawa J., Miller F. J., O'Neil J. J. Single-breath diffusing capacity and lung volumes in small laboratory mammals. J Appl Physiol Respir Environ Exerc Physiol. 1980 Jun;48(6):1052–1059. doi: 10.1152/jappl.1980.48.6.1052. [DOI] [PubMed] [Google Scholar]
  54. Turek Z., Kreuzer F., Ringnalda B. E. Blood gases at several levels of oxygenation in rats with a left-shifted blood oxygen dissociation curve. Pflugers Arch. 1978 Aug 25;376(1):7–13. doi: 10.1007/BF00585241. [DOI] [PubMed] [Google Scholar]
  55. Vinegar A., Sinnett E. E., Leith D. E. Dynamic mechanisms determine functional residual capacity in mice, Mus musculus. J Appl Physiol Respir Environ Exerc Physiol. 1979 May;46(5):867–871. doi: 10.1152/jappl.1979.46.5.867. [DOI] [PubMed] [Google Scholar]
  56. Vízek M., Palecek F. Effect of anaesthesia on the pattern of breathing. Physiol Bohemoslov. 1977;26(5):417–423. [PubMed] [Google Scholar]
  57. Webb H. H., Tierney D. F. Experimental pulmonary edema due to intermittent positive pressure ventilation with high inflation pressures. Protection by positive end-expiratory pressure. Am Rev Respir Dis. 1974 Nov;110(5):556–565. doi: 10.1164/arrd.1974.110.5.556. [DOI] [PubMed] [Google Scholar]
  58. Wong K. L., Alarie Y. A method for repeated evaluation of pulmonary performance in unanesthetized, unrestrained guinea pigs and its application to detect effects of sulfuric acid mist inhalation. Toxicol Appl Pharmacol. 1982 Mar 30;63(1):72–90. doi: 10.1016/0041-008x(82)90028-x. [DOI] [PubMed] [Google Scholar]
  59. Young S. L., Tierney D. F., Clements J. A. Mechanism of compliance change in excised rat lungs at low transpulmonary pressure. J Appl Physiol. 1970 Dec;29(6):780–785. doi: 10.1152/jappl.1970.29.6.780. [DOI] [PubMed] [Google Scholar]

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