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Toxicological Sciences 61, 356-367 (2001)
Copyright © 2001 by the Society of Toxicology


RESPIRATORY TOXICOLOGY

Canines as Sentinel Species for Assessing Chronic Exposures to Air Pollutants: Part 2. Cardiac Pathology

L. Calderón-Garcidueñas*,{dagger},1, T. M. Gambling{ddagger}, H. Acuña{dagger}, R. García{dagger}, N. Osnaya{dagger}, S. Monroy{dagger}, A. Villarreal-Calderón{dagger}, J. Carson{ddagger}, H. S. Koren§ and R. B. Devlin§

* Curriculum in Toxicology, University of North Carolina, Chapel Hill, North Carolina 27599–7310; {dagger} Instituto Nacional de Pediatría, Mexico City 14410; {ddagger} Center for Environmental Medicine and Lung Biology, University of North Carolina, Chapel Hill, North Carolina 27599–7310; and § National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711

The principal objective of this study is to evaluate by light and electron microscopy (LM, EM) the heart tissues in stray southwest and northeast metropolitan Mexico City (SWMMC, NEMMC) dogs and compare their findings to those from 3 less polluted cities (Cuernavaca, Tlaxcala, and Tuxpam). Clinically healthy mongrel dogs, including 109 from highly polluted SWMMC and NEMMC, and 43 dogs from less polluted cities were studied. Dogs residing in cities with lower levels of pollutants showed little or no cardiac abnormalities. Mexico City and Cuernavaca dogs exhibited LM myocardial alterations including apoptotic myocytes, endothelial and immune effector cells, degranulated mast cells associated with scattered foci of mononuclear cells in left and right ventricles and interventricular septum, and clusters of adipocytes interspersed with mononuclear cells. Vascular changes included scattered polymorphonuclear leukocytes (PMN) margination and microthrombi in capillaries, and small venous and arteriolar blood vessels. Small veins exhibited smooth muscle cell hyperplasia, and arteriolar blood vessels showed deposition of particulate matter (PM) in the media and adventitia. Unmyelinated nerve fibers showed endoneural and epineural degranulated mast cells. EM examination of myocardial mast cells showed distended and abundant rough endoplasmic reticulum with few secretory granules. Myocardial capillaries exhibited fibrin deposition and their endothelial cells displayed increased luminal and abluminal pinocytic activity and the formation of anemone-like protrusions of the endothelium into the lumen. A close association between myocardial findings, lung epithelial and endothelial pathology, and chronic inflammatory lung changes was noted. The myocardial changes described in dogs exposed to ambient air pollutants may form the basis for developing hypothesis-driven mechanistic studies that might explain the epidemiological data of increased cardiovascular morbidity and mortality in people exposed to air pollutants.

Key Words: ambient air pollution; dogs; myocardium; mast cells; particulate matter; ozone; apoptotic myocytes and endothelial cells; endothelial injury; Mexico City.


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