Impaired vascular function after exposure to diesel exhaust generated at urban transient running conditions

Abstract

Background: Traffic emissions including diesel engine exhaust are associated with increased respiratory and cardiovascular morbidity and mortality. Controlled human exposure studies have demonstrated impaired vascular function after inhalation of exhaust generated by a diesel engine under idling conditions.

Objectives: To assess the vascular and fibrinolytic effects of exposure to diesel exhaust generated during urban-cycle running conditions that mimic ambient 'real-world' exposures.

Methods: In a randomised double-blind crossover study, eighteen healthy male volunteers were exposed to diesel exhaust (approximately 250 microg/m3) or filtered air for one hour during intermittent exercise. Diesel exhaust was generated during the urban part of the standardized European Transient Cycle. Six hours post-exposure, vascular vasomotor and fibrinolytic function was assessed during venous occlusion plethysmography with intra-arterial agonist infusions.

Measurements and main results: Forearm blood flow increased in a dose-dependent manner with both endothelial-dependent (acetylcholine and bradykinin) and endothelial-independent (sodium nitroprusside and verapamil) vasodilators. Diesel exhaust exposure attenuated the vasodilatation to acetylcholine (P < 0.001), bradykinin (P < 0.05), sodium nitroprusside (P < 0.05) and verapamil (P < 0.001). In addition, the net release of tissue plasminogen activator during bradykinin infusion was impaired following diesel exhaust exposure (P < 0.05).

Conclusion: Exposure to diesel exhaust generated under transient running conditions, as a relevant model of urban air pollution, impairs vasomotor function and endogenous fibrinolysis in a similar way as exposure to diesel exhaust generated at idling. This indicates that adverse vascular effects of diesel exhaust inhalation occur over different running conditions with varying exhaust composition and concentrations as well as physicochemical particle properties. Importantly, exposure to diesel exhaust under ETC conditions was also associated with a novel finding of impaired of calcium channel-dependent vasomotor function. This implies that certain cardiovascular endpoints seem to be related to general diesel exhaust properties, whereas the novel calcium flux-related effect may be associated with exhaust properties more specific for the ETC condition, for example a higher content of diesel soot particles along with their adsorbed organic compounds.

Figure 1

The urban sequence of the European Transient Cycle applied in the present study.

Figure 2

Mass size distribution of diluted diesel exhaust particles in the exposure chamber during the urban running part of the European Trancient Cycle. MMD_a for the fine mode was 0.116 μm.

Figure 3

Number size distribution of diluted diesel exhaust particles in the exposure chamber during the urban running part of the European Transient Cycle. Standard deviations for 3 scans are shown as error bars. A log-normal fitting calculation showed that the size distribution comprised in principal only one single mode.

Figure 4

Forearm blood flow measured six hours after diesel exhaust (solid line) and filtered air (dashed line) exposure during unilateral intra-brachial infusion of bradykinin (Bk), acetylcholine (Ach), sodium nitroprusside (SNP) and verapamil (Vp) in infused and non-infused (dotted lines) arms. Effect of exposure compared with using 2-way ANOVA with repeated measures. Data plotted as mean ± SEM. P-values are given for diesel exhaust exposure vs. air.

Figure 5

Net release of t-PA antigen in the infused arm during unilateral intra-brachial infusion of bradykinin (Bk) after diesel (solid line) and air (dashed line) exposures. Effect of exposure compared using 2-way ANOVA with repeated measures. Data plotted as mean ± SEM.

Figure 6

Relative distribution (in % of total PAH) for specific particulate associated PAH compounds for the present ETC running conditions in comparison with idling conditions used in previous studies [12,14].

Figure 7

Relative distribution (in % of total PAH) for specific semi-volatile PAH compounds for the present ETC running conditions in comparison with idling conditions used in previous studies [12,14].