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Examining the role of TRPA1 in air pollution-induced cardiac arrhythmias and autonomic imbalance
Citation:
Hazari, M. AND A. Farraj. Examining the role of TRPA1 in air pollution-induced cardiac arrhythmias and autonomic imbalance. Society of Toxicology Meeting, New Orleans, LA, March 14 - 17, 2016.
Impact/Purpose:
This abstract describes the cardiovascular effects of air pollution and the role of TRPA1, a physiological "environmental sensor", in the response.
Description:
Here we describe how air pollution causes cardiac arrhythmogenesis through sensory irritation in the airways. Time-series studies show the risk of adverse cardiac events increases significantly in the hours to days after exposure to air pollution. Although activation of sensory neural arcs and autonomic imbalance have been proposed as an important mechanism of air pollution-induced cardiovascular dysfunction, little data exists on the specific pathways that mediate these sudden cardiovascular outcomes (e.g. arrhythmia). Neural sensory networks play a role in not only the immediate response to a pollutant, but also an autonomic shift that renders the host susceptible to adverse cardiovascular events in the hours after exposure. TRPA1 is a suitable candidate for initiating these mechanisms given it functions as an environmental sensor of several ubiquitous environmental chemicals and is localized to nociceptive nerve fibers that trigger autonomic reflex arcs and subsequent physiological changes. Using radiotelemetry and ex-vivo cardiac reperfusion, we measured cardiac function in wild-type and TRPA1-knockout mice exposed to 3ppm acrolein. Our results show that a single inhalation exposure to acrolein causes TRPA1-dependent non-conducted p-wave arrhythmias, sinus node dysfunction, and a significant increase in heart rate variability (SDNN/RMSSD), suggesting disruption of the normal electrical signal and altered autonomic modulation, respectively. TRPA1 also mediated a 50% increase in left ventricular developed pressure (LVDP), a measure of cardiac mechanical function, 24 hours after exposure. Furthermore, our studies in rats show that diesel exhaust (150 ug/m3) exposure increases sensitivity to the pro-arrhythmogenic drug aconitine through TRPA1 and autonomic sympathetic modulation. Taken together, these data show that TRPA1 mediates cardiac arrhythmia during air pollution exposure and increases the risk of arrhythmogenesis after exposure. On the other hand, it may also cause disruption of the autonomic control of the cardiovascular system and compensatory mechanical changes, both of which are latent alterations that make the host susceptible to triggered adverse events. In conclusion, although the role of TRPA1 appears to be clear, these data point to the complexity and dynamic nature of these neurophysiological pathways that transduce inhalation of air pollution into cardiovascular effects. This abstract does not reflect USEPA policy