Acute Exposure to Diesel Exhaust Increases Muscle Sympathetic Nerve Activity in Humans

Abstract

Background Diesel exhaust (DE) emissions are a major contributor to ambient air pollution and are strongly associated with cardiovascular morbidity and mortality. Exposure to traffic-related particulate matter is linked with acute adverse cardiovascular events; however, the mechanisms are not fully understood. We examined the role of the autonomic nervous system during exposure to DE that has previously only been indirectly investigated. Methods and Results Using microneurography, we measured muscle sympathetic nerve activity (MSNA) directly in the peroneal nerve of 16 healthy individuals. MSNA, heart rate, and respiration were recorded while subjects rested breathing filtered air, filtered air with an exposure mask, and standardized diluted DE (300 µg/m³) through the exposure mask. Heart rate variability was assessed from an ECG. DE inhalation rapidly causes an increase in number of MSNA bursts as well as the size of bursts within 10 minutes, peaking by 30 minutes (P<0.001), compared with baseline filtered air with an exposure mask. No significant changes occurred in heart rate variability indices during DE exposure; however, MSNA frequency correlated negatively with total power (r²=0.294, P=0.03) and low frequency (r²=0.258, P=0.045). Heart rate correlated positively with MSNA frequency (r²=0.268, P=0.04) and the change in percentage of larger bursts (burst amplitude, height >50% of the maximum burst) from filtered air with an exposure mask (r²=0.368, P=0.013). Conclusions Our study provides direct evidence for the rapid modulation of the autonomic nervous system after exposure to DE, with an increase in MSNA. The quick increase in sympathetic outflow may explain the strong epidemiological data associating traffic-related particulate matter to acute adverse cardiovascular events such as myocardial infarction. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02892279.

Keywords: air pollution; autonomic nervous system; diesel; heart rate variability; muscle sympathetic nerve activity; sympatho‐excitation.

Figure 1. Experimental protocol. Subjects sat semisupine for 1 hour while parameters were recorded.

In the first 10 minutes, subjects were exposed to filtered air (baseline), after which nose plugs and the exposure masks were fitted, and they continued to breath filtered air for a further 10 minutes (mask baseline). The filtered air was then switched to the diluted diesel exhaust air mixture, and recordings were made for a further 40 minutes. For analysis, the experiment was broken down into 10‐minute blocks, and the median 5 minutes of each block were analyzed for muscle sympathetic nerve activity (MSNA) frequency (bursts/min), burst incidence (bursts/100 heart beats [hb]), and MSNA amplitude (burst height, µV) and area (µV/ms). Mins indicates minutes.

Figure 2. Experimental recordings of muscle sympathetic nerve activity, ECG, and respiration in one representative subject at mask baseline (A) and after 25 minutes of breathing diluted diesel exhaust (B).

RMS indicates root mean squared.

Figure 3. Changes in muscle sympathetic nerve activity (MSNA) during exposure to diluted diesel exhaust.

A, MSNA burst frequency. B, MSNA burst incidence. C, Average normalized MSNA burst area. D, MSNA burst amplitude (height). E, Burst area. For percentage of normalized bursts that were greater than half of the maximum burst for each individual subject. Bars represent mean with 95% CI. Significance ***P<0.001, **P<0.01, *P<0.05, repeated‐measures 1‐way ANOVA, with Geisser‐Greenhouse correction, and Tukey’s multiple comparison test. BL indicates baseline; and mins, minutes.

Figure 4. The mean difference with 95% CIs for muscle sympathetic nerve activity (MSNA) burst frequency (A).

B, MSNA burst incidence. C, Average normalized MSNA burst area. D, MSNA burst amplitude (height). E, Burst area. For percentage of normalized bursts that were greater than half of the maximum burst for each individual subject. BL indicates baseline. D0–10 indicates DE exposure between 0 to 10 min​s; D10–20 the DE exposure from 10 to 20 mins; D20–30 the DE exposure from 20 to 30 mins; and D30–40 the DE exposure from 30 to 40 mins.

Figure 5. Relationship between muscle sympathetic nerve activity (MSNA) frequency and total power (A), low frequency (LF) (B), standard deviation of NN intervals (SDNN) (C), and heart rate 20 to 30 minutes after diesel exhaust inhalation (D).

Pearson correlation coefficient tests were used and the line fitted using nonlinear regression with least squares fit.

Figure 6. Relationship between MSNA amplitude (burst height), the percentage of bursts >50% of the maximum burst amplitude compared with heart rate.

Data plotted are the differences from mask baseline for the 20‐ to 30‐minute time point values. Pearson correlation coefficient test was used and the line fitted using nonlinear regression with least squares fit.