Los Angeles, CA - It's well appreciated that air pollution can worsen lung diseases and, probably through a generalized inflammatory response, cardiovascular disease as well; but that apparently isn't all there is to what dirty air can do to the heart and blood vessels.

Some laboratory evidence suggests that ultrafine particles (UFP), a component of air pollution that comes primarily from motor vehicles, can cross into the circulation from the alveoli and have direct toxic effects outside the lungs, observed Dr Robert A Kloner (Good Samaritan Hospital, Los Angeles, CA).

Elaborating for heartwire on a "state-of-the-art paper" published in the August 26, 2008 issue of the Journal of the American College of Cardiology [1], of which he is a coauthor, Kloner said "the previous thinking was that these ultrafine particles went to the lungs, and the lungs got inflamed, then they generated toxic cytokines, and it was the toxic cytokines that caused the cardiac damage. Our experiments suggest that there actually may be a more direct effect of the particles on the vasculature and the heart."

The article, with lead author Dr Boris Z Simkhovich (Good Samaritan Hospital), is in large part a selective review of key, often epidemiologic evidence for acute and chronic damaging effects from exposure to air pollutants. Sometimes the effects are measured in terms of hospital admissions for pulmonary or cardiovascular disorders. Other studies have directly tied increased air-particle concentrations to adverse changes in heart rate and HR variability, blood pressure, endothelial function, and blood coagulability.

Notably, according to Kloner, one study with about 4500 participants found an inverse relationship between the distance of a person's residence from a main road (and car emissions) and degree of coronary artery calcification at noninvasive imaging. "I think that's a very sobering finding."

Less covered in the literature, however, is evidence that pollution particles can directly affect the heart and vessels, independent of any mechanism involving the lungs.

Research by Kloner's group and other teams, including experiments conducted on isolated, perfused rat hearts, have suggested that direct injection of UFPs into the circulation, without any lung involvement, "can decrease coronary blood flow and decrease contractility of the ventricles, and we've also seen when you give these acutely you get an increase in arrhythmias," Kloner said.

Other work by various teams suggests that air pollution can provoke an inflammatory response in the lungs through the generation of reactive oxygen species (ROS), which have long been shown to have different acute and chronic effects on the heart in various clinical settings, the review from Simkhovich et al notes. They theorize that if UFPs do enter the circulation from the lungs, they may affect cardiovascular function by promoting ROS directly in the vessels and heart.

"We think that oxygen radical production by these particles might be important, and certainly that they could worsen inflammation and cause damage in the blood vessels and stimulate atherosclerosis," according to Kloner. The idea was supported by work from his group, reported as a poster at the American College of Cardiology 2008 Scientific Sessions [2], in which infusions of an antioxidant agent reversed or attenuated impairments in coronary flow and contractile function induced by the direct administration of UFP in isolated, perfused rat hearts.

That observation, according to Kloner, raises at least the theoretical possibility of some kind of antioxidant therapy against the cardiovascular effects of air pollution. Currently the most important "therapy" for susceptible individuals, especially patients with coronary or pulmonary disease, consists of minimizing exposure. That, he said, might include avoiding outdoor exercise on days when air pollution is especially bad and staying indoors altogether when it's most severe.

But could there be other therapies? "Is it possible, for example, that patients with coronary disease should take antioxidants on days when there are high levels of pollution? I don't know the answer, but I know that experimentally, at least, we have preliminary data suggesting that antioxidants might at least reduce the effect the particles have on coronary flow."

1. Simkhovich BZ, Kleinman MT, Kloner RA. Air pollution and cardiovascular injury. Epidemiology, toxicology, and mechanisms. J Am Coll Cardiol 2008; 52:719-726.
2. Hwang H, Simkhovich BZ, Kleinman MT, Kloner RA. The direct toxic effect of ultrafine particles in coronary flow: the importance of the hydroxyl radical. J Am Coll Cardiol 2008; 51 (suppl A):A303.