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International audience; Arrhythmias following cardiac stress are a key predictor of death in healthy population. Carbon monoxide (CO) is a ubiquitous pollutant promoting oxidative stress and associated with hospitalization for cardiovascular disease and cardiac mortality. We investigated the effect of chronic CO exposure on the occurrence of arrhythmic events after a cardiac stress test and the possible involvement of related oxidative stress. Wistar rats exposed chronically (4 weeks) to sustained urban CO pollution presented more arrhythmic events than controls during recovery after cardiac challenge with isoprenaline in vivo. Sudden death occurred in 22% of CO-exposed rats versus 0% for controls. Malondialdehyde (MDA), an end-product of lipid peroxidation, was increased in left ventricular tissue of CO-exposed rats. Cardiomyocytes isolated from CO-exposed rats showed higher reactive oxygen species (ROS) production (measured with MitoSox Red dye), higher diastolic Ca(2+) resulting from SR calcium leak and an higher occurrence of irregular Ca(2+) transients (measured with Indo-1) in comparison to control cells after a high pacing sequence. Acute treatment with a ROS scavenger (N-acetylcysteine, 20 mmol/L, 1 h) prevented this sequence of alterations and decreased the number of arrhythmic cells following high pacing. Chronic CO exposure promotes oxidative stress that alters Ca(2+) homeostasis (through RYR2 and SERCA defects) and thereby mediates the triggering of ventricular arrhythmia after cardiac stress that can lead to sudden death.

PURPOSE. To assess the associations of plasma lutein and zeaxanthin and other carotenoids with the risk of age-related maculopathy (ARM) and cataract in the population-based Pathologies Oculaires Liees a l'Age (POLA) Study. METHODS. Retinal photographs were graded according to the international classification. ARM was defined by the presence of late ARM (neovascular ARM, geographic atrophy) and/or soft indistinct drusen (>125 μm) and/or soft distinct drusen (>125 μm) associated with pigmentary abnormalities. Cataract classification was based on a direct standardized lens examination at the slit lamp, according to Lens Opacities Classification System III. Plasma carotenoids were measured by high-performance liquid chromatography (HPLC), in 899 subjects of the cohort. RESULTS. After multivariate adjustment, the highest quintile of plasma zeaxanthin was significantly associated with reduced risk of ARM (OR = 0.07; 95% CI: 0.01-0.58; P for trend = 0.005), nuclear cataract (OR = 0.23; 95% CI: 0.08-0.68; P for trend = 0.003) and any cataract (OR = 0.53; 95% CI: 0.31-0.89; P for trend = 0.01). ARM was significantly associated with combined plasma lutein and zeaxanthin (OR = 0.21; 95% CI: 0.05- 0.79; P for trend = 0.01), and tended to be associated with plasma lutein (OR = 0.31; 95% CI: 0.09-1.07; P for trend = 0.04), whereas cataract showed no such associations. Among other carotenoids, only β-carotene showed a significant negative association with nuclear cataract, but not ARM. CONCLUSIONS. These results are strongly suggestive of a protective role of the xanthophylls, in particular zeaxanthin, for the protection against ARM and cataract.