Impact/Purpose:

This research supports efforts to develop an animal model of high bronchospasmic activity to ascertain a potential role for neurogenic mediation of airway and cardiac physiologic effects.

Description:

Reports in the literature have attributed altered heart rate, heart rate variability, and rhythm to inhaled particulate matter (PM) in humans. Whereas the changes in heart rate are very small, analysis of ECG tracings indicate changes in HRV suggesting altered autonomic balance. These alterations seem to be greater in the elderly who may have underlying sensitivity to autonomic imbalance. It is unclear whether these changes result from direct PM effects on the heart, via humoral signals originating from lung injury, or via neural sensory networks. Given the known reductions in heart rate associated with sensory and pulmonary irritants, we hypothesized that these cardiac changes may result from systemic autonomic responses to irritants acting on the airways. Because the guinea pig has a strong bronchoconstrictive response to sensory irritants, we elected to use this model to evaluate the impact of sensory irritation on cardiac function and its neural association with bronchoconstriction. However, this model requires updating because of significant changes in strain derivation and advances in measurement methods. Muti-colored guinea pigs from Elm Hill Labs were evaluated for sensitivity to SO2 as a prototype irritant. Concentration-response curves were characterized to identify a concentration that would induce significant bronchoconstriction. A concentration appropriate to achieve consistent bronchoconstriction (100 ppm) was found to be about an order of magnitude higher than that originally described. However, because the intent was to link the airway responses to cardiac responses, the environmental relevance of this concentration was not of primary concern. This work showed that bronchoconstriction and bradycardia coexisted with SO2 stimulation although the temporal responses were different. As sensory irritants are thought to function via the NANC C-fiber network, we used capsaicin to functionally denervate the guinea pigs and repeated the exposure studies. Ablation of C-fiber function resulted in complete blockage of both the airway and cardiac responses. Future studies will involve irritant aerosol - gas interactions that have been shown to have potentiative irritant interactions and will evaluate more detailed pharmacologic dissection of the parasympathetic origins of the irritant response as well as the sympathetic compensatory rebound.

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