Abstract
A system was developed for exposure of unanesthetized mice to airborne chemicals and for continuous measurement of their breathing pattern prior to, during and following exposure. By measuring inspiratory and expiratory airflows (VI and VE), and integration with time to yield tidal volume (VT), we obtained characteristic modifications to the normal breathing pattern. These permitted recognition that a specific portion of the respiratory tract was affected by the selected airborne chemicals. Following recognition, we also quantitated the degree of effect using one specific measurement in each case. An effect on the upper respiratory tract, induced by the sensory irritant, 2-chlorobenzylchloride, was quantitated by measuring a decrease in respiratory frequency. An effect on the conducting airways, induced by the airway constrictor, carbamylcholine, was quantitated by a decrease in VE at the mid-point of VT. An effect at the alveolar level, induced either by the vagal nerve ending stimulant, propranolol, or by the pulmonary irritant, machining fluid G, was quantitated by an increase in the length of a pause induced at the end of expiration. The system is easy to construct and operate and can be used to rapidly evaluate the effects of airborne chemicals on the respiratory tract.
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References
Alarie Y (1966) Irritating properties of airborne chemicals to the upper respiratory tract. Arch Environ Health 13: 433–449
Alarie Y (1973) Sensory irritation by airborne chemicals. CRC Crit Rev Toxicol 2: 299–363
Alarie Y (1981) Toxicologic evaluation of airborne chemical irritants and allergens using respiratory reflex reactions. In: Leong BKJ (ed) Proceedings of inhalation toxicology and technology symposium. Ann Arbor Science, Ann Arbor, MI, pp 207–231
Alarie Y, Schaper M (1988) Pulmonary performance in laboratory animals exposed to toxic agents and correlation with lung disease in humans. In: Loke J (ed) Pathophysiology and treatment of inhalation injuries. Marcel Dekker, NY, pp 67–122
Alarie Y, Ulrich CE, Haddock RH, Jennings HJ (1971) Measurement of the mechanical properties of the lung in cynomolgus monkeys with digital computerization. Arch Environ Health 22: 643–654
Alarie Y, Iwasaki M, Schaper M (1990) Whole-body plethysmography in sedentary or exercise conditions to determine pulmonary toxicity, including hypersensitivity induced by airborne toxicants. J Am Coll Toxicol 9: 407–439
Amdur MO, Mead J (1958) Mechanics of respiration in unanesthetized guinea pigs. Am J Physiol 192: 364–368
Barrow CS, Alarie Y, Warrick J, Stock M (1977) Comparison of the sensory irritation response in mice to chlorine and hydrogen chloride. Arch Environ Health 32: 68–76
Bartlett JE Jr (1986) Upper airway motor system. In: Cherniack NS, Widdicombe JG (eds) Handbook of physiology. Section 3. The respiratory system. American Physiological Society, Bethesda, MD, pp 753–754
Boggs DF (1992) Comparative control of respiration. In: Parent RA (ed) Comparative biology of the normal lung. CRC Press, Boca Raton FL, pp 309–341
Coleridge HM, Coleridge JCG (1986) Reflexes evoked from tracheobronchial tree and lungs. In: Cherniack NS, Widdicombe JG (eds) Handbook of physiology. Section 3, respiration. American Physiological Society, Bethesda, MD, pp 395–429
Crossfill ML, Widdicombe JG (1961) Physical characteristics of the chest and lungs and the work of breathing in different mammalian species. J Physiol 158: 1–14
Draper NR, Smith H (1981) Applied regression analysis. John Wiley and Sons, NY
Dudek BR, Short RD, Brown MA, Rolloff MV (1992) Structure activity relationships of a series of sensory irritants. J Toxicol Environ Hlth 37: 511–518
Ferguson JS, Schaper M, Stock MF, Weyel DA, Alarie Y (1986) Sensory and pulmonary irritation with exposure to methyl isocyanate. Toxicol Appl Pharmacol 82: 329–335
Joyner MJ, Jilka SM, Taylor JA, Kalis JK, Nittolo J, Hicks RW, Lohman TG, Wilmore JH (1987) β-Blockade reduces tidal volume during heavy exercise in trained and untrained men. J Appl Physiol 62: 1819–1825
Lawson EE, Richter DW, Czyzyk-Krzeska MF, Bischoff A, Rudesill RC (1991) Respiratory neuronal activity during apnea and other breathing patterns induced by laryngeal stimulation. J Appl Physiol 70: 2742–2749
Matsumoto S, Kanno T, Yamasaki M, Nagayama T, Shimizu T (1992) Pulmonary C-fibers elicit both apneusis and tachypnea in the rabbit. Respir Physiol 87: 165–181
Mead J (1960) Control of respiratory frequency. J Appl Physiol 15: 325–336
Nielsen GD (1991) Mechanism of activation of the sensory irritant receptor by airborne chemicals. CRC Crit Rev Toxicol 21: 183–208
Paintal AS (1969) Mechanism of stimulation of typeJ receptors. J Physiol 203: 511–532
Paintal AS (1981) Effects of drugs on chemoreceptors, pulmonary and cardiovascular receptors. In: Widdicombe JG (ed) International encyclopedia of pharmacology and therapeutics, Section 104, respiratory pharmacology. Pergamon Press, Oxford, pp 217–239
Rebuck AS, Slutsky AS (1986) Control of breathing in diseases of the respiratory tract and lungs. In: Cherniack NS, Widdicombe JG (eds) Handbook of physiology, section 3, the respiratory system. American Physiological Society, Bethesda, MD, pp 771–792
Remmers JE, Richter DW, Ballantyne D, Bainton CR, Klein JP (1986) Reflex prolongation of stage I of expiration. Plugers Arch 407: 190–198
Richter DW, Ballantyne D, Remmers JE (1986) How is the respiratory rhythm generated? A model. NIPS 1: 109–112
Schaper M (1993) Development of a database for sensory irritants and its use in establishing occupational exposure limits. Am Ind Hyg Assoc J (in press)
Schaper M, Alarie Y (1985) The effects of aerosols of carbamylcholine, serotonin and propranolol on the ventilatory response to CO2 in guinea pigs and comparison with the effects of histamine and sulfuric acid. Acta Pharmacol Toxicol 56: 244–249
Schaper M, Alarie Y (1988) Induction of abnormal ventilatory response to CO2 and evaluation of agents to prevent or reverse these responses. Fundam Appl Toxicol 10: 506–516
Schaper M, Brost M (1991) The respiratory effects of trimellitic anhydride aerosols in mice. Arch Toxicol 65: 671–677
Schaper M, Detwiler K (1991) Evaluation of the acute respiratory effects of aerosolized machining fluids in mice. Fundam Appl Toxicol 16: 309–319
Schaper M, Thompson R, Alarie Y (1985) A method to classify airborne chemicals which alter the normal ventilatory response induced by CO2. Toxicol Appl Pharmacol 79: 332–341
Schaper M, Detwiler K, Alarie Y (1989) Alteration of respiratory cycle timing by propranolol. Toxicol Appl Pharmacol 97: 538–547
Sinnet EE, Jackson AC, Leith DE, Butler JP (1981) Fast integrated flow plethysmograph for small mammals. J Appl Physiol 50: 1104–1110
Vinegar A, Sinnett EE, Leith DE (1979) Dynamic mechanisms determine functional residual capacity in mice,Mus Musculis. J Appl Physiol 46: 867–871
Von Euler C (1992) Brain stem mechanisms for generation and control of breathing pattern. In: Cherniack NS, Widdicombe JG, (eds) Hand-book of physiology. Section 3. The respiratory system. American Physiological Society, Bethesda, MD, pp 1–67
Weyel DA, Schaffer RB (1985) Pulmonary and sensory irritation of diphenyl4,4′ and dicyclohexylmethane-4,4′diisocyanate. Toxicol Appl Pharmacol 77: 427–433
Widdicombe JG, Tatar M (1988) Upper airway reflex control. Ann NY Acad Sci 533: 252–260
Wong KL, Alarie Y (1982) 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 63: 72–90
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Vijayaraghavan, R., Schaper, M., Thompson, R. et al. Characteristic modifications of the breathing pattern of mice to evaluate the effects of airborne chemicals on the respiratory tract. Arch Toxicol 67, 478–490 (1993). https://doi.org/10.1007/BF01969919
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DOI: https://doi.org/10.1007/BF01969919