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Carbon Monoxide Pollution Promotes Cardiac Remodeling and Ventricular Arrhythmia in Healthy Rats

Abstract : Rationale: Epidemiologic studies associate atmospheric carbon monoxide (CO) pollution with adverse cardiovascular outcomes and increased cardiac mortality risk. However, there is a lack of data regarding cellular mechanisms in healthy individuals. Objectives: To investigate the chronic effects of environmentally relevant CO levels on cardiac function in a well-standardized healthy animal model. Methods : Wistar rats were exposed for 4 weeks to filtered air (CO < 1 ppm) or air enriched with CO (30 ppm with five peaks of 100 ppm per 24-h period), consistent with urban pollution. Myocardial function was assessed by echocardiography and analysis of surface ECG and in vitro by measuring the excitation-contraction coupling of single left ventricular cardiomyocytes. Measurements and Main Results: Chronic CO pollution promoted left ventricular interstitial and perivascular fibrosis, with no change in cardiomyocyte size, and had weak, yet significant, effects on in vivo cardiac function. However, both contraction and relaxation of single cardiomyocytes were markedly altered. Several changes occurred, including decreased Ca2+ transient amplitude and Ca2+ sensitivity of myofilaments and increased diastolic intracellular Ca2+ subsequent to decreased SERCA-2a expression and impaired Ca2+ reuptake. CO pollution increased the number of arrhythmic events. Hyperphosphorylation of Ca2+-handling and sarcomeric proteins, and reduced responses to β-adrenergic challenge were obtained, suggestive of moderate CO-induced hyperadrenergic state. Conclusions: Chronic CO exposure promotes a pathological phenotype of cardiomyocytes in the absence of underlying cardiomyopathy. The less severe phenotype in vivo suggests a role for compensatory mechanisms. Arrhythmia propensity may derive from intracellular Ca2+ overload.
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https://hal.umontpellier.fr/hal-01824352
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Soumis le : mercredi 15 avril 2020 - 10:42:05
Dernière modification le : vendredi 15 mai 2020 - 12:22:08

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Lucas André, Julien Boissière, Cyril Reboul, Romain Perrier, Santiago Zalvidea, et al.. Carbon Monoxide Pollution Promotes Cardiac Remodeling and Ventricular Arrhythmia in Healthy Rats. American Journal of Respiratory and Critical Care Medicine, American Thoracic Society, 2010, 181 (6), pp.587-595. ⟨10.1164/rccm.200905-0794OC⟩. ⟨hal-01824352⟩

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