Abstract
Cardiopulmonary function was assessed four and six months after Fischer 344 rats were exposed to 2 hr to 0, 3, or 10 ppm methyl isocyanate (MIC). During assessment, the rats were challenged with 4 and 8% carbon dioxide (CO2) to stimulate ventilatory drive. Minute ventilation (VE) during CO2 challenge was increased in MIC-treated rats compared to controls when examined 4 months after exposure to 10 ppm MIC, suggesting a ventilation/perfusion inequality. An increase in maximum expiratory flow and a decrease in expiratory time indicated increased lung recoil in these rats. Evidence of pulmonary hypertension was observed in electrocardiograms (ECGs) and supported by postmortem analysis that showed a positive association between increased ECG abnormalities and increased right ventricular weights in the rats treated with 10 ppm MIC. At 6 months, forced expiratory flow-volume curves indicated persistent airway obstruction; however, no changes in inspiratory or expiratory resistance were evident. Decreased dynamic compliance and changes in two new measures of lung function (volume and time at zero expiratory intrapleural pressure) suggest that MIC-induced lung dysfunction also exhibited elements of a restrictive disease.
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Selected References
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- Adkins B., Jr, O'Connor R. W., Dement J. M. Inhalation exposure system used for acute and repeated-dose methyl isocyanate exposures of laboratory animals. Environ Health Perspect. 1987 Jun;72:45–51. doi: 10.1289/ehp.877245. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Alarie Y., Ferguson J. S., Stock M. F., Weyel D. A., Schaper M. Sensory and pulmonary irritation of methyl isocyanate in mice and pulmonary irritation and possible cyanidelike effects of methyl isocyanate in guinea pigs. Environ Health Perspect. 1987 Jun;72:159–167. doi: 10.1289/ehp.8772159. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bucher J. R., Boorman G. A., Gupta B. N., Uraih L. C., Hall L. B., Stefanski S. A. Two-hour methyl isocyanate inhalation exposure and 91-day recovery: a preliminary description of pathologic changes in F344 rats. Environ Health Perspect. 1987 Jun;72:71–75. doi: 10.1289/ehp.877271. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bucher J. R., Gupta B. N., Adkins B., Jr, Thompson M., Jameson C. W., Thigpen J. E., Schwetz B. A. Toxicity of inhaled methyl isocyanate in F344/N rats and B6C3F1 mice. I. Acute exposure and recovery studies. Environ Health Perspect. 1987 Jun;72:53–61. doi: 10.1289/ehp.877253. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Costa D. L., Kutzman R. S., Lehmann J. R., Drew R. T. Altered lung function and structure in the rat after subchronic exposure to acrolein. Am Rev Respir Dis. 1986 Feb;133(2):286–291. doi: 10.1164/arrd.1986.133.2.286. [DOI] [PubMed] [Google Scholar]
- Dorato M. A., Carlson K. H., Copple D. L. Pulmonary mechanics in conscious Fischer 344 rats: multiple evaluations using nonsurgical techniques. Toxicol Appl Pharmacol. 1983 May;68(3):344–353. doi: 10.1016/0041-008x(83)90277-6. [DOI] [PubMed] [Google Scholar]
- Drazen J. M. Physiologic basis and interpretation of common indices of respiratory mechanical function. Environ Health Perspect. 1976 Aug;16:11–16. doi: 10.1289/ehp.761611. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ferguson J. S., Schaper M., Stock M. F., Weyel D. A., Alarie Y. Sensory and pulmonary irritation with exposure to methyl isocyanate. Toxicol Appl Pharmacol. 1986 Feb;82(2):329–335. doi: 10.1016/0041-008x(86)90209-7. [DOI] [PubMed] [Google Scholar]
- Jaeger R. J., Sussman R. G., Gearhart J. M., Bowers A. B., Shore R. E., Sellakumar A. R. Repeated pulmonary function evaluation following bleomycin treatment. J Toxicol Environ Health. 1983 Mar;11(3):415–423. doi: 10.1080/15287398309530355. [DOI] [PubMed] [Google Scholar]
- Kamat S. R., Mahashur A. A., Tiwari A. K., Potdar P. V., Gaur M., Kolhatkar V. P., Vaidya P., Parmar D., Rupwate R., Chatterjee T. S. Early observations on pulmonary changes and clinical morbidity due to the isocyanate gas leak at Bhopal. J Postgrad Med. 1985 Apr;31(2):63–72. [PubMed] [Google Scholar]
- 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]
- Martin-Body R. L., Sinclair J. D. Analysis of respiratory patterns in the awake and in the halothane anaesthetised rat. Respir Physiol. 1985 Jul;61(1):105–113. doi: 10.1016/0034-5687(85)90032-5. [DOI] [PubMed] [Google Scholar]
- Michael J. R., Kennedy T. P., Buescher P., Farrukh I., Lodato R., Rock P. C., Gottlieb J., Gurtner G., de la Monte S. M., Hutchins G. M. Nitrendipine attenuates the pulmonary vascular remodeling and right ventricular hypertrophy caused by intermittent hypoxia in rats. Am Rev Respir Dis. 1986 Mar;133(3):375–379. doi: 10.1164/arrd.1986.133.3.375. [DOI] [PubMed] [Google Scholar]
- Stevens M. A., Fitzgerald S., Ménache M. G., Costa D. L., Bucher J. R. Functional evidence of persistent airway obstruction in rats following a two-hour inhalation exposure to methyl isocyanate. Environ Health Perspect. 1987 Jun;72:89–94. doi: 10.1289/ehp.877289. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Watkinson W. P., Brice M. A., Robinson K. S. A computer-assisted electrocardiographic analysis system: methodology and potential application to cardiovascular toxicology. J Toxicol Environ Health. 1985;15(6):713–727. doi: 10.1080/15287398509530700. [DOI] [PubMed] [Google Scholar]
- Weissberg R. M., Marian J., Bradshaw J. Respiratory and cardiovascular effects of prostaglandins in the conscious guinea pig. J Pharmacol Exp Ther. 1976 Jul;198(1):197–208. [PubMed] [Google Scholar]
- Wiester M. J., Setzer C. J., Barry B. E., Mercer R. R., Grady M. A. Inhalation studies of Mt. St. Helens volcanic ash in animals: respiratory mechanics, airway reactivity and deposition. Environ Res. 1985 Feb;36(1):230–240. doi: 10.1016/0013-9351(85)90020-9. [DOI] [PubMed] [Google Scholar]
