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

André, Lucas; Boissière, Julien; Reboul, Cyril; Perrier, Romain; Zalvidea, Santiago; Meyer, Grégory; Thireau, Jérôme; Tanguy, Stéphane; Bideaux, Patrice; Hayot, Maurice; Boucher, François; Obert, Philippe; Cazorla, Olivier; Richard, Sylvain

doi:10.1164/rccm.200905-0794oc

Cited by 87 publications

(90 citation statements)

References 56 publications

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“…The chief mechanisms underlying the ability of CO to scavenge ROS have yet to be explored. CO could appear to act via oxidative stress since it reduced the activity of several antioxidant enzymes [30]. This effect on antioxidant enzymes, however, is not always observed [18].…”

Section: Discussionmentioning

confidence: 98%

Carbon Monoxide Protects Against Ischemia-reperfusion Injuryin Vitrovia Antioxidant Properties

Berne¹,

Lauzier²,

Rochette³

et al. 2012

Cell Physiol Biochem

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Carbon monoxide (CO) is believed to mediate many of the cytoprotective effects attributed to the activation of heme oxygenase (HO-1), the enzyme responsible for CO production. Recently, the study of CO-releasing molecules (CO-RMs) has provided a new approach for the delivery of CO. In the present study, we examined whether the cardioprotective properties of CO-RM2 in isolated rat hearts subjected to an ischemia-reperfusion (I/R) sequence were associated with the presence of CO. In addition, the antioxidant properties of CO-RM2 were evaluated. In hearts pretreated with CO-RM2, the improvement in contractile function at the end of the reperfusion period after 20 min of global total ischemia was significantly greater than in controls. These beneficial effects were accompanied by a reduction in 1) LDH activity release 2) infarct size 3) ventricular superoxide production. The improvement in myocardial function and the reduction in oxidative stress were not observed when hearts were pretreated with inactivated CO-RM2 (iCO-RM2). Additionally, CO-RM2, but not iCO-RM2, was found to exert antioxidant properties. These results suggest that the production of CO is a necessary factor in the cardioprotective and antioxidant actions of CO-releasing compound. These results may open up new ground for a novel class of cardioprotective compounds.

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Section: Discussionmentioning

confidence: 98%

Carbon Monoxide Protects Against Ischemia-reperfusion Injuryin Vitrovia Antioxidant Properties

Berne¹,

Lauzier²,

Rochette³

et al. 2012

Cell Physiol Biochem

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“…We propose that ranolazine or related drugs that act by inhibiting the late Na 1 current may have therapeutic benefit in such cases. In summary, the present study has identified the molecular basis for the proarrhythmic effects of acute CO exposure, which is distinct from chronic CO-induced remodeling of cardiac function (6) and is increasingly recognized as a common phenomenon of clinical importance. We also provide compelling evidence that CO exposure in vivo can, particularly during additional stress, such as increased b adrenergic stimulation, lead to fatal arrhythmias.…”

Section: Cardiac Namentioning

confidence: 89%

“…Chronic exposure to moderate (30-200 ppm) CO can induce myocardial injury and fibrosis (3)(4)(5)(6). However, acute environmental (e.g., road traffic) (7) exposure to CO (up to 500 ppm) is associated with arrhythmias and an increased risk of sudden death (3,8), particularly in patients with existing cardiac conditions (9,10).…”

mentioning

confidence: 99%

Carbon Monoxide Induces Cardiac Arrhythmia via Induction of the Late Na⁺ Current

Dallas¹,

Yang

Boyle³

et al. 2012

Am J Respir Crit Care Med

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Rationale: Clinical reports describe life-threatening cardiac arrhythmias after environmental exposure to carbon monoxide (CO) or accidental CO poisoning. Numerous case studies describe disruption of repolarization and prolongation of the QT interval, yet the mechanisms underlying CO-induced arrhythmias are unknown. Objectives: To understand the cellular basis of CO-induced arrhythmias and to indentify an effective therapeutic approach. Methods: Patch-clamp electrophysiology and confocal Ca 21 and nitric oxide (NO) imaging in isolated ventricular myocytes was performed together with protein S-nitrosylation to investigate the effects of CO at the cellular and molecular levels, whereas telemetry was used to investigate effects of CO on electrocardiogram recordings in vivo. Measurements and Main Results: CO increased the sustained (late) component of the inward Na 1 current, resulting in prolongation of the action potential and the associated intracellular Ca 21 transient. In more than 50% of myocytes these changes progressed to early after-depolarization-like arrhythmias. CO elevated NO levels in myocytes and caused S-nitrosylation of the Na 1 channel, Na v 1.5. All proarrhythmic effects of CO were abolished by the NO synthase inhibitor L-NAME, and reversed by ranolazine, an inhibitor of the late Na 1 current. Ranolazine also corrected QT variability and arrhythmias induced by CO in vivo, as monitored by telemetry. Conclusions: Our data indicate that the proarrhythmic effects of CO arise from activation of NO synthase, leading to NO-mediated nitrosylation of Na V 1.5 and to induction of the late Na 1 current. We also show that the antianginal drug ranolazine can abolish CO-induced early after-depolarizations, highlighting a novel approach to the treatment of CO-induced arrhythmias.

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“…Andre and colleagues exposed Wistar rats to either filtered air (CO , 1 ppm) or air enriched with CO (30 ppm with five peaks of 100 ppm per 24-h period) for 4 weeks and evaluated the myocardial function by echocardiography and EKG and in vitro by measuring the excitationcontraction coupling of single left ventricular cardiomyocytes (40). They found that CO caused fibrosis in the left ventricle and a small reduction in cardiac function and increased the number of arrhythmias in vivo.…”

Section: Carbon Monoxidementioning

confidence: 99%

Update in Environmental and Occupational Medicine 2010

Budinger

Mutlu²

2011

Am J Respir Crit Care Med

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

Abstract: 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 Ca(2+) overload.

Cited by 87 publications

References 56 publications

Carbon Monoxide Protects Against Ischemia-reperfusion Injuryin Vitrovia Antioxidant Properties

Carbon Monoxide Protects Against Ischemia-reperfusion Injuryin Vitrovia Antioxidant Properties

Carbon Monoxide Induces Cardiac Arrhythmia via Induction of the Late Na⁺ Current

Update in Environmental and Occupational Medicine 2010

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

Abstract: 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 Ca(2+) overload.

Cited by 87 publications

References 56 publications

Carbon Monoxide Protects Against Ischemia-reperfusion Injuryin Vitrovia Antioxidant Properties

Carbon Monoxide Protects Against Ischemia-reperfusion Injuryin Vitrovia Antioxidant Properties

Carbon Monoxide Induces Cardiac Arrhythmia via Induction of the Late Na+ Current

Update in Environmental and Occupational Medicine 2010

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Carbon Monoxide Induces Cardiac Arrhythmia via Induction of the Late Na⁺ Current