In the healthy rat, prolonged exposure to carbon monoxide (CO) under conditions that mimic urban pollution leads to changes to cardiac morphology and function. Compensatory mechanisms develop in these animals to sustain normal cardiac activity, but they become more vulnerable to heart disease. These results, published on 15 March 2010 in the American Journal of Respiratory and Critical Care Medicine by CNRS and INSERM researchers, thus provide cellular proof in the rat of a direct effect of urban pollution on cardiac function. Studies are ongoing to verify these findings in humans.
Epidemiological studies have linked atmospheric carbon monoxide (CO) pollution, such as that seen in cities, to adverse cardiovascular outcomes and an increased cardiac mortality risk, notably in subjects weakened by an underlying condition. However, in healthy subjects, the effects of CO are poorly understood and the cellular mechanisms little studied.
CNRS researchers in Laboratoire UMR-637 (INSERM/Université Montpellier 1 & 2), working in collaboration with researchers from Université d'Avignon, exposed healthy rats for four weeks to pure air or to air enriched in CO at a level reproducing the conditions of urban pollution. The aim of this study was to assess the effects of chronic CO pollution on cardiac function in a healthy experimental model, both in vivo, using echocardiography and electrocardiograms (ECG), and in vitro by measuring different parameters in cardiomyocytes (cardiac cells).
The results revealed that chronic CO pollution caused changes to cardiac morphology and function. In rats in the CO group, the effects of these differences were observed at the level of the left ventricle, together with localized signs of stress and cardiac remodeling. At the cellular level, cardiomyocytes displayed contractility defects and arrhythmic events. A moderate "hyperadrenergic" state, which reveals stress and is known for its implication in the development of cardiac hypertrophy and fibrosis, tachycardia and the risk of sudden cardiac death, was also observed. Finally, an impairment of calcium handling by cardiomyocytes was also demonstrated, which could trigger extrasystoles and ventricular tachycardia, with a risk of sudden death.
In healthy rats, chronic exposure to CO thus led to cellular alterations that are normally seen in a context of heart failure. The less severe in vivo phenotype suggested that compensatory mechanisms had developed. By "canceling out" the effects of CO, they enabled the myocardium to function normally. But they placed the cardiac cells under a chronic state of stress, so that if an additional stress occurred, such as myocardial infarction, the consequences for the heart would be more severe. The same two research teams (Avignon and Montpellier) have also recently shown that chronic exposure to CO increases the cardiac damage induced by myocardial infarction to a very significant degree.
At a diagnostic level, and if these results can be extrapolated to humans, this study shows that the harmful effects of CO pollution may be difficult to detect using routine clinical investigations such as echocardiography or short ECG recordings, because they are mainly observed under conditions of stress and at the cellular level. Nevertheless, preliminary findings appear to indicate that in healthy humans, after an exercise test, there is a correlation between the carboxyhemoglobin level in the blood (representative of atmospheric CO that can be analyzed in a simple blood sample) and the onset of arrhythmic events.
Current studies are trying to determine under which conditions, and after what duration of exposure, the cellular effects observed here could cause more severe pathological effects in vivo in animals, and then in humans.
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