Carbon monoxide exposure enhances arrhythmia after cardiac stress: involvement of oxidative stress

Abstract

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.

Biphasic Response of Mitochondrial Biogenesis to Oxidative Stress in Visceral Fat of Diet-Induced Obesity Mice

“…The mitochondrial ROS in AT was performed as previously described (2). Frozen fat tissue cross sections from CD-and HFHSD-fed mice were evaluated by measuring the level of mitochondrial superoxide (O 2 -) production quantified by MitoSox Red kit (Molecular probe, Invitrogen).…”

Carbon monoxide exposure in the urban environment: An insidious foe for the heart?

“…It is well documented that the binding of CO to cytochrome-c oxidase in the electron transport chain, as well as the interaction of CO with NO synthase (Heusch et al, 2010), generates reactive oxygen and nitrogen species (ROS and RNS) (Ide et al, 1999;Kaiser, 2005). Recently, we have shown that chronic CO exposure decreases the activity of the antioxidant enzymes superoxide dismutase, catalase, and glutathione peroxidase, increases that of thioredoxin reductase, and increases levels of malondialdehyde, the end-product of lipid peroxidation by ROS, thus confirming the presence of CO-induced oxidative stress (Andre et al, , 2011. These are all features that are typical of ventricular myocytes isolated from failing hearts.…”

“…Following exposure mimicking urban CO pollution, the Hb CO level of the animals was 4-6% on leaving the container but it was normalized to 2% after several hours. Despite these low CO concentrations, the animals developed pathological cardiac remodelling characterized by an increase of both posterior wall thickness and left ventricular fibrous tissue, without dilatation or hemodynamic changes (Andre et al, , 2011.…”

“…We have explored the effects of chronic exposure to CO levels under conditions mimicking urban air pollution on the cardiac function of healthy rats in vivo, ex vivo and at the cardiomyocyte level (Andre et al, , 2011Farah et al, 2010;Meyer et al, 2010). Our primary approach consisted of exposing healthy rats to a basal CO concentration of 30 ppm (1.2 × 10 −6 mol L −1 ) during 12 h every day, with five 1-h periods at 100 ppm (4.16 × 10 −6 mol L −1 ) included, for 4 weeks.…”

“…The increase in diastolic Ca 2+ levels observed after chronic CO exposure is often the trigger for signalling pathways involved in gene expression under pathophysiological situations (Andre et al, , 2011Bye et al, 2008). In addition, it provides a good substrate for arrhythmogenic events, as shown by the increase in ectopic ventricular beats observed in CO-exposed rats at rest when compared to controls (Andre et al, , 2011.…”