Induction of abnormal ventilatory responses to CO2 and evaluation of agents given to prevent or reverse these responses

Abstract

This study demonstrates how a previously described animal model can be utilized to evaluate the effects of multiple aerosols. For the exposures presented in this report, unanesthetized but mildly restrained guinea pigs were used. Airflow (V), tidal volume (VT), and respiratory frequency (f) were continuously measured in all animals and their flow-volume (V-VT) loops were also obtained. The animals were first exposed to room air and then challenged with a 10% CO2 (in 19% O2, 71% N2) mixture. The normal ventilatory response to 10% CO2 consists of increases in V, VT, and f. This response is very stable for long periods of time and is highly reproducible. It is possible, however, to alter the normal CO2 response by adding an aerosol to the CO2 mixture. Two types of acute responses can be induced, Type I and Type II. In this study, histamine and carbamylcholine aerosols were used to induce the Type I response while propranolol aerosols were used to induce the Type II response. Serotonin aerosols were used to induce both types of effects. We report that the bronchodilator, isoproterenol, reversed the Type I pulmonary effects where the level of reversal was dependent upon isoproterenol concentration. The rapid, shallow breathing, characteristic of the Type II response, was not reversed by isoproterenol but could be prevented by blocking the vagus nerve with cocaine. Since no invasive techniques are required and the same animals can be used repeatedly, combinations of aerosols can be tested in order to delineate how Type I or Type II abnormal ventilatory responses to CO2 are induced by a wide variety of airborne chemicals.