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

Abstract

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.

Inhalation of concentrated ambient air particles exacerbates myocardial ischemia in conscious dogs.

“…Particulate exposure may enhance occlusion-induced ischemia by increasing the resistance or reactivity of collateral blood vessels. This notion is supported by recent evidence of particulaterelated vascular changes: a) Increased circulating levels of the vasoactive peptide endothelin have been reported in rats (Bouthillier et al 1998;Vincent et al 2001a) and in healthy adults (Vincent et al 2001b) exposed to urban particles; b) endothelial cell activation by ultrastructural criteria was noted in the coronary vasculature of dogs from high pollution areas but not in those from low pollution areas (Calderon-Garciduenas et al 2001); c) acute brachial artery vasoconstriction has been reported in humans after exposure to CAPs and ozone (Brooke et al 2002); and d) vasoconstriction of pulmonary and coronary (Godleski JJ. Unpublished observations) vessels has been observed in CAPs-exposed rats.…”

Particulate Matter Exposure Impairs Systemic Microvascular Endothelium-Dependent Dilation

“…In support of this possibility, PM has been reported to enter the systemic circulation. PM deposition in the arteriolar wall has been documented in stray Mexico City canines (Calderon-Garciduenas et al 2001). Inhaled ultrafine 13 C particles have been shown to translocate to extrapulmonary organs (Oberdorster et al 2002).…”

Rat cardiac mast cell maturation and differentiation following acute ventricular volume overload

“…These results, together with our fi ndings, suggest that perturbations to the heart elicited by volume overload or ischemic insult, may regulate local stem cell factor production or release, thereby promoting maturation and differentiation of resident immature cardiac mast cells. The likelihood of a paracrine factor mediating the induction of cardiac mast cell maturation is further bolstered by the reports indicating increased cardiac mast cell numbers in rats following 2 days of inhalation exposure to diesel exhaust particles [27] and in free-roaming dogs chronically exposed to air pollutants [28].…”