Sensory Irritation Response in Rats II: Recovery and Dose-Dependence

Abstract

Inhaled irritants can cause respiratory depression by simulating trigeminal nerves in the nasal cavity. This decrease in inhalation rate results in a decrease in the rate of the irritant gases flowing to the stimulated nerves, creating a complex feedback response. Previously, a model was created to describe how the presence of formaldehyde affects respiration in the rat. This ordinary differential equation model incorporated a model of the physiology of the upper respiratory tract of the rat and a model of the neurological control of the respiration rate due to signaling from the stimulated nerves in the nasal cavity. However, an optimal fit to data was not fully established. In the current study, the fit of the previously established model is reevaluated while incorporating the recovery of the ventilation rate after the end of exposure. Additionally, the dose-dependence of the adaptation time allowed by the previous model is more fully quantified, and the updated model predicts formaldehyde data well. Not only are the results of the previous study improved, the model is also shown to predict ventilation decrease in response to other irritants, specifically acrolein, ammonia, and sulfur dioxide. The model is expected to translate to predictions of other irritants with minor parameter changes.