Carbon monoxide pollution promotes cardiac remodeling and ventricular arrhythmia in healthy rats.
BACKGROUND
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.


OBJECTIVE
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.


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 Ca(2+) transient amplitude and Ca(2+) sensitivity of myofilaments and increased diastolic intracellular Ca(2+) subsequent to decreased SERCA-2a expression and impaired Ca(2+) reuptake. CO pollution increased the number of arrhythmic events. Hyperphosphorylation of Ca(2+)-handling and sarcomeric proteins, and reduced responses to beta-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 Ca(2+) overload.
Andre
Lucas
L
INSERM U, CHU Arnaud de Villeneuve, Montpellier, France.
Boissière
Julien
J
Reboul
Cyril
C
Perrier
Romain
R
Zalvidea
Santiago
S
Meyer
Gregory
G
Thireau
Jérôme
J
Tanguy
Stéphane
S
Bideaux
Patrice
P
Hayot
Maurice
M
Boucher
François
F
Obert
Philippe
P
Cazorla
Olivier
O
Richard
Sylvain
S
D000393:Air Pollutants / Q000633:toxicity*; D000397:Air Pollution / Q000009:adverse effects*; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced*; D002248:Carbon Monoxide / Q000633:toxicity*; D002374:Catalase / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D004562:Electrocardiography; D005979:Glutathione Peroxidase / Q000187:drug effects / Q000378:metabolism; D006352:Heart Ventricles / Q000000981:diagnostic imaging / Q000187:drug effects; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000187:drug effects / Q000378:metabolism; D014463:Ultrasonography; D020257:Ventricular Remodeling / Q000187:drug effects*
D000393:Air Pollutants; D002248:Carbon Monoxide; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase