NEW APPROACHES IN PULMONARY FUNCTION EVALUATION TO DETECT THE EFFECTS OF AIRBORNE CHEMICALS (BRONCHOCONSTRICTION, CARBON DIOXIDE VENTILATORY RESPONSE, REFLEX RESTRICTION, FLOW-VOLUME LOOPS, PRESSURE-VOLUME)

A new method is proposed in this report to evaluate the pulmonary effects of aerosols using unanesthetized, minimally-restrained guinea pigs. To conduct inhalation exposures, each animal was fitted with a head chamber and positioned within a whole-body plethysmograph. Air or other mixtures passed continuously through the head chamber while respiratory frequency (f), airflow (V), and tidal volume ((DELTA)P, VT) were measured. (DELTA)P denoted plethysmographic pressure changes proportional to tidal volume, while VT was obtained via integration of V. Pressure-volume and flow-volume loops were also evaluated.;Stable ventilatory responses were found in animals breathing air and were magnified by introducing a 10% CO(,2) mixture (18% O(,2), 72% N(,2)). If a histamine, carbamylcholine, serotonin, propranolol or sulfuric acid aerosol was added to 10% CO(,2), then alterations of the normal ventilatory response to CO(,2) occurred. Concentration-dependent reductions in tidal volume were evoked by addition of these aerosols to CO(,2). That concentration of each chemical capable of completely abolishing normal increases in tidal volume induced by CO(,2) (AC(,100)) was determined. The descending order of biological potency, based on AC(,100) values, was as follows: histamine, carbamylcholine, serotonin, propranolol, and sulfuric acid. Histamine was almost 100 times as potent as sulfuric acid.;Effects of the five aerosols on f, V and loops were not uniform and from the data, it was concluded that these aerosols must interact with different receptors. Two classes of chemicals were defined that both decrease tidal volume but in different ways. Type I chemicals act upon smooth muscle in conducting airways to produce "obstruction". Resistance to airflow is increased and interruptions in airflow are seen. Type II chemicals evoke "reflex restriction", probably via stimulation of Type J vagal nerve endings. Increases in f and V are induced by Type II chemicals. Isoproterenol is an effective antagonist for Type I chemicals, but not for Type II chemicals. At the AC(,100) level, histamine, sulfuric acid and carbamylcholine were considered Type I chemicals, while propranolol was considered a Type II chemical. Serotonin evoked obstruction and reflex restriction consecutively and thus was dually-classified.;In summary, the new method permitted rapid evaluation of pulmonary effects of aerosols. It was as sensitive as the method described by Amdur and Mead (1958) and it appears that human responses can be predicted from the animal model.