Citation:

Carll, A., R. Lust, M. Hazari, C. Perez, Todd Krantz, C. King, D. Winsett, W. Cascio, D. Costa, AND A. Farraj. Diesel Exhaust Inhalation Increases Cardiac Output, Bradyarrhythmias, and Parasympathetic Tone in Aged Heart Failure-Prone Rats. TOXICOLOGICAL SCIENCES. Society of Toxicology, RESTON, VA, 131(2):583-95, (2013).

Impact/Purpose:

A single inhalation exposure to DE in aged heart failure-prone rats caused LV dilation and changes in cardiac physiology. Our findings demonstrate that age in a heart failure-prone rat strain confers overt susceptibility to the effects of air pollutant exposure on arrhythmia, repolarization, and HRV. Most of the observed physiologic changes correlated with increased HRV markers of parasympathetic influence, suggesting autonomic modulation played an important role in the observations. The precise mechanism by which increased parasympathetic influence may relate to such effects requires further study. Taken together, these findings provide insight on the health effects of air pollution, particularly the mechanisms mediating the exacerbation of heart failure. This is particularly relevant to the agency as an increased understanding of the mechanisms by which air pollutants trigger adverse effects in susceptible populations will reduce uncertainty in standard setting.

Description:

Acute air pollutant inhalation is linked to adverse cardiac events and death, and hospitalizations for heart failure. Diesel exhaust (DE) is a major air pollutant suspected to exacerbate preexisting cardiac conditions, in part, through autonomic and electrophysiologic disturbance of normal cardiac function. To explore this putative mechanism, we examined cardiophysiologic responses to DE inhalation in an aged rat model of heart failure. We hypothesized that acute DE exposure would alter heart rhythm, cardiac electrophysiology, and ventricular performance and dimensions consistent with autonomic imbalance, while increasing biochemical markers of toxicity. Aged Spontaneously Hypertensive Heart Failure rats (SHHF, 16 months) were exposed once to whole DE (4 hours, target PM2.5 concentration: 500 µg/m3) or filtered air. DE increased multiple heart rate variability (HRV) parameters during exposure. In the 4 hours after exposure, DE increased cardiac output, left ventricular volume (end diastolic and systolic), stroke volume, HRV, and atrioventricular (AV) block arrhythmias while increasing electrocardiographic measures of ventricular repolarization (i.e., ST- and T-amplitudes, ST area, Tpeak-Tend duration). DE did not affect heart rate relative to Air. Post-exposure changes in arrhythmia, repolarization, and echocardiography positively correlated with HRV. At 24 hours post-exposure, DE-exposed rats had increased serum C-reactive protein and pulmonary eosinophils. This study demonstrates that the adverse cardiac effects of DE inhalation in heart failure may occur through autonomic imbalance associated with disruptions of cardiac electrophysiology and left ventricular dilation.

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