Biological plausibility for carbon monoxide as a copollutant in PM epidemiologic studies

Several recent epidemiologic studies investigating the short-term effects o f particulate matter (PM) concentrations have shown carbon monoxide (CO) to have the strongest and most consistent statistical relationship with hospi tal admissions for cardiac diseases. This article suggests a potential hypo thesis for these epidemiologic observations. Oxygen (O-2) is transported, i n reversible combination with hemoglobin, from the lungs to the tissues, wh ere it diffuses into cardiac myocytes. Within the myocyte a portion of the O-2 diffuses directly to the mitochondria, while the remaining O-2 is trans ported by facilitated diffusion bound to myoglobin, a heme protein found in muscle. Within the mitochondria, O-2 reacts to produce adenosine triphosph ate (ATP), a high-energy phosphate compound that provides energy for all ce ll functions. Accordingly, the sustained production of ATP depends on the c ontinuous delivery of O-2 to the mitochondria, and failure at any point in the O-2 transport system will compromise ATP production and myocardial func tion. Myoglobin, a fundamental constituent of cardiac muscle is essential f or delivering O-2 to the mitochondria. Myoglobin concentrations in cardiac tissue were 50% lower in patients with heart failure than in patients dying from noncardiac causes. Myoglobin concentrations are also severely depress ed in animal models of congestive heart failure. Consequently, the role of myoglobin as a cellular transporter of O-2 is seriously impaired by heart d isease. Carbon monoxide reduces O-2 transport to the tissues and, within th e tissues, binds with myoglobin to form carboxymyoglobin (COMb). Thus, in c ardiac patients CO further exacerbates the disease-related loss of myoglobi n function. This further disrupts O-2 transport and promotes adverse conseq uences for the compromised heart. Moreover, during hypoxia CO has the prope nsity of leaving the blood and binding with myoglobin in the intracellular compartment. Elderly persons with preexisting cardiopulmonary disorders app ear to be at maximum risk of harmful health effects due to ambient air poll ution exposure. Many of these disorders result in generalized or regional h ypoxia. It is reasonable to hypothesize that CO also moves out of the blood of these patients and into the heart tissue whenever they are under hypoxi c stress, such as exercise. Accordingly, CO binds with the marginal myoglob in concentrations present in the hearts of cardiac patients and further com promiser cardiac function, resulting in poor tolerance of activity. Therefo re, reduced cardiac myoglobin in people with heart disease, further exacerb ated by CO moving into the cardiac tissue during episodes of hypoxia, may a ccount for the positive association between ambient CO concentrations and h ospitalization for heart disease.