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. 2004 Jun;112(8):872–878. doi: 10.1289/ehp.6583

Emission-particle-induced ventilatory abnormalities in a rat model of pulmonary hypertension.

Sarah Y Gardner 1, John K McGee 1, Urmila P Kodavanti 1, Allen Ledbetter 1, Jeffrey I Everitt 1, Darrell W Winsett 1, Donald L Doerfler 1, Daniel L Costa 1
PMCID: PMC1242015  PMID: 15175175

Abstract

Preexistent cardiopulmonary disease in humans appears to enhance susceptibility to the adverse effects of ambient particulate matter. Previous studies in this laboratory have demonstrated enhanced inflammation and mortality after intratracheal instillation (IT) and inhalation (INH) of residual oil fly ash (ROFA) in a rat model of pulmonary hypertension induced by monocrotaline (MCT). The present study was conducted to examine the effects of ROFA in this model on ventilatory function in unanesthetized, unrestrained animals. Sixty-day-old male CD rats were injected with MCT (60 mg/kg) or vehicle (VEH) intraperitoneally 10 days before IT of ROFA (8.3 mg/kg) or saline (SAL) (control) or nose-only INH of ROFA [15 mg/m3 for 6 hr on 3 consecutive days or air (control)]. At 24 and 72 hr after exposure, rats were studied individually in a simultaneous gas uptake/whole-body plethysmograph. Lungs were removed at 72 hr for histology. Pulmonary test results showed that tidal volume (VT) decreased 24 hr after IT of ROFA in MCT-treated rats. Breathing frequency, minute volume (VE), and the ventilatory equivalent for oxygen increased in MCT- and VEH-treated rats 24 hr after IT or INH of ROFA and remained elevated 72 hr post-IT. O2 uptake (VO2) decreased after IT of ROFA in MCT-treated rats. Carbon monoxide uptake decreased 24 hr after IT of ROFA, returning to control values in VEH-treated rats but remaining low in MCT-treated rats 72 hr post-IT. ROFA exposure induced histologic changes and abnormalities in several ventilatory parameters, many of which were enhanced by MCT treatment.

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Selected References

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  1. Burnett R. T., Dales R., Krewski D., Vincent R., Dann T., Brook J. R. Associations between ambient particulate sulfate and admissions to Ontario hospitals for cardiac and respiratory diseases. Am J Epidemiol. 1995 Jul 1;142(1):15–22. doi: 10.1093/oxfordjournals.aje.a117540. [DOI] [PubMed] [Google Scholar]
  2. Campen Matthew J., Nolan Julianne P., Schladweiler Mette C. J., Kodavanti Urmila P., Costa Daniel L., Watkinson William P. Cardiac and thermoregulatory effects of instilled particulate matter-associated transition metals in healthy and cardiopulmonary-compromised rats. J Toxicol Environ Health A. 2002 Oct 25;65(20):1615–1631. doi: 10.1080/00984100290071694. [DOI] [PubMed] [Google Scholar]
  3. Costa D. L., Dreher K. L. Bioavailable transition metals in particulate matter mediate cardiopulmonary injury in healthy and compromised animal models. Environ Health Perspect. 1997 Sep;105 (Suppl 5):1053–1060. doi: 10.1289/ehp.97105s51053. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Dreher K. L., Jaskot R. H., Lehmann J. R., Richards J. H., McGee J. K., Ghio A. J., Costa D. L. Soluble transition metals mediate residual oil fly ash induced acute lung injury. J Toxicol Environ Health. 1997 Feb 21;50(3):285–305. [PubMed] [Google Scholar]
  5. Dye J. A., Lehmann J. R., McGee J. K., Winsett D. W., Ledbetter A. D., Everitt J. I., Ghio A. J., Costa D. L. Acute pulmonary toxicity of particulate matter filter extracts in rats: coherence with epidemiologic studies in Utah Valley residents. Environ Health Perspect. 2001 Jun;109 (Suppl 3):395–403. doi: 10.1289/ehp.01109s3395. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Hauser R., Elreedy S., Hoppin J. A., Christiani D. C. Airway obstruction in boilermakers exposed to fuel oil ash. A prospective investigation. Am J Respir Crit Care Med. 1995 Nov;152(5 Pt 1):1478–1484. doi: 10.1164/ajrccm.152.5.7582280. [DOI] [PubMed] [Google Scholar]
  7. Kodavanti U. P., Jackson M. C., Ledbetter A. D., Richards J. R., Gardner S. Y., Watkinson W. P., Campen M. J., Costa D. L. Lung injury from intratracheal and inhalation exposures to residual oil fly ash in a rat model of monocrotaline-induced pulmonary hypertension. J Toxicol Environ Health A. 1999 Aug 27;57(8):543–563. doi: 10.1080/009841099157502. [DOI] [PubMed] [Google Scholar]
  8. Kodavanti U. P., Jaskot R. H., Su W. Y., Costa D. L., Ghio A. J., Dreher K. L. Genetic variability in combustion particle-induced chronic lung injury. Am J Physiol. 1997 Mar;272(3 Pt 1):L521–L532. doi: 10.1152/ajplung.1997.272.3.L521. [DOI] [PubMed] [Google Scholar]
  9. Kodavanti U. P., Schladweiler M. C., Ledbetter A. D., Watkinson W. P., Campen M. J., Winsett D. W., Richards J. R., Crissman K. M., Hatch G. E., Costa D. L. The spontaneously hypertensive rat as a model of human cardiovascular disease: evidence of exacerbated cardiopulmonary injury and oxidative stress from inhaled emission particulate matter. Toxicol Appl Pharmacol. 2000 May 1;164(3):250–263. doi: 10.1006/taap.2000.8899. [DOI] [PubMed] [Google Scholar]
  10. Lai Y. L., Olson J. W., Gillespie M. N. Ventilatory dysfunction precedes pulmonary vascular changes in monocrotaline-treated rats. J Appl Physiol (1985) 1991 Feb;70(2):561–566. doi: 10.1152/jappl.1991.70.2.561. [DOI] [PubMed] [Google Scholar]
  11. Meyrick B., Gamble W., Reid L. Development of Crotalaria pulmonary hypertension: hemodynamic and structural study. Am J Physiol. 1980 Nov;239(5):H692–H702. doi: 10.1152/ajpheart.1980.239.5.H692. [DOI] [PubMed] [Google Scholar]
  12. Meyrick B., Reid L. Development of pulmonary arterial changes in rats fed Crotalaria spectabilis. Am J Pathol. 1979 Jan;94(1):37–50. [PMC free article] [PubMed] [Google Scholar]
  13. Poloniecki J. D., Atkinson R. W., de Leon A. P., Anderson H. R. Daily time series for cardiovascular hospital admissions and previous day's air pollution in London, UK. Occup Environ Med. 1997 Aug;54(8):535–540. doi: 10.1136/oem.54.8.535. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Pope C. A., 3rd, Schwartz J., Ransom M. R. Daily mortality and PM10 pollution in Utah Valley. Arch Environ Health. 1992 May-Jun;47(3):211–217. doi: 10.1080/00039896.1992.9938351. [DOI] [PubMed] [Google Scholar]
  15. Schwartz J., Dockery D. W. Increased mortality in Philadelphia associated with daily air pollution concentrations. Am Rev Respir Dis. 1992 Mar;145(3):600–604. doi: 10.1164/ajrccm/145.3.600. [DOI] [PubMed] [Google Scholar]
  16. Schwartz J., Morris R. Air pollution and hospital admissions for cardiovascular disease in Detroit, Michigan. Am J Epidemiol. 1995 Jul 1;142(1):23–35. doi: 10.1093/oxfordjournals.aje.a117541. [DOI] [PubMed] [Google Scholar]
  17. Schwartz J. What are people dying of on high air pollution days? Environ Res. 1994 Jan;64(1):26–35. doi: 10.1006/enrs.1994.1004. [DOI] [PubMed] [Google Scholar]
  18. Watkinson W. P., Campen M. J., Costa D. L. Cardiac arrhythmia induction after exposure to residual oil fly ash particles in a rodent model of pulmonary hypertension. Toxicol Sci. 1998 Feb;41(2):209–216. doi: 10.1006/toxs.1997.2406. [DOI] [PubMed] [Google Scholar]
  19. Wichmann H. E., Mueller W., Allhoff P., Beckmann M., Bocter N., Csicsaky M. J., Jung M., Molik B., Schoeneberg G. Health effects during a smog episode in West Germany in 1985. Environ Health Perspect. 1989 Feb;79:89–99. doi: 10.1289/ehp.897989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. 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]
  21. Wordley J., Walters S., Ayres J. G. Short term variations in hospital admissions and mortality and particulate air pollution. Occup Environ Med. 1997 Feb;54(2):108–116. doi: 10.1136/oem.54.2.108. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Yokoyama E. A simple method for measuring the respiratory uptake of carbon monoxide in unanesthetized rats: an application to rats acutely exposed to ozone. Arch Environ Health. 1984 Sep-Oct;39(5):375–378. doi: 10.1080/00039896.1984.10545867. [DOI] [PubMed] [Google Scholar]

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