Abstract Body (Do not enter title and authors here): Introduction. Epidemiological evidence suggests a link between acute air pollution exposure and ventricular arrhythmias, with increased reactive oxygen species (ROS) production as a key mechanism. However, a cause-effect relationship remains unclear, studies on chronic effects are lacking, and the impact of strategies limiting ROS production has not been studied in detail.
Aims. To analyze the effects of chronic intratracheal instillation of diesel exhaust particles (DEPs) on ventricular arrhythmogenesis, investigate the underlying mechanisms, and assess the impact of cerium oxide nanoparticles (CeO₂NP) as a ROS-detoxifying strategy.
Methods. Male and female Sprague-Dawley rats were intratracheally instilled with saline without or with DEPs (7.5 g/Kg, 0.375 mL/Kg, 3 times/week, for 1-3 weeks). Rats were then sacrificed and hearts perfused through the aorta in a Langendorff system. Incidence of premature ventricular beats (PVBs) and non-sustained and sustained (>30s) ventricular tachyarrhythmias (VT) were assessed by programmed electrical stimulation. Cardiac hypertrophy, collagen content, inflammation and oxidative stress were analyzed by conventional histology, Western Blot, RT-PCR, and the oxidized/reduced glutathione (GSH/GSSG) ratio. The potential protective effect of ROS-detoxifying CeO₂NP (0.5 mg/Kg/week, i.p.) was also analyzed.
Results. DEP exposure increased the incidence and duration of inducible sustained VTs. This pro-arrhythmic effect associated with a moderate rise in interstitial collagen deposition (from 3.11±0.12 in controls to 4.80±0.21 % in DEP-exposed rats, Student’s t test, p<0.001) and prolonged QRS complex and QTc in the ECG. Collagen expression was induced within one weeks of DEP exposure, as shown by RT-PCR. Additionally, the GSH/GSSG ratio decreased after 3 weeks of DEP exposure, while mRNA levels of the ROS-producing NOX1, NOX2 and NOX4 isoforms rose early after DEP exposure, and expression of the antioxidant thioredoxin reductase was reduced. CeO₂NP attenuated the pro-arrhythmic effects of DEP exposure (sustained VT duration: 0.00±0.00, 51.09±18.99 and 20.00±20.00 ms in hearts from control, DEP-treated and CeO₂-treated animals, Krustal-Wallis test, p<0.05 between controls and DEP-treated).
Conclusion. DEP exposure increases the incidence and duration of sustained VTs in rats, effects associated with increased collagen deposition and oxidative stress. ROS-detoxifying CeO₂NP attenuate the pro-arrhythmic effects of DEP exposure.