Inhaled Environmental Combustion Particles Cause Myocardial Injury in the Wistar Kyoto Rat

Abstract

Epidemiologists have associated particulate matter (PM) air pollution with cardiovascular morbidity and premature mortality worldwide. However, experimental evidence demonstrating causality and pathogenesis of particulate matter (PM)-induced cardiovascular damage has been insufficient. We hypothesized that protracted, repeated inhalation by rats of oil combustion-derived, fugitive emission PM (EPM), similar in metal composition to selected sources of urban air PM, causes exposure duration- and dose-dependent myocardial injury in susceptible rat strains. Zinc was the only primary water-leachable/bioavailable element of this EPM. Male Sprague-Dawley (SD), Wistar Kyoto (WKY), and spontaneously hypertensive (SH) rats were exposed nose-only to EPM (2, 5, or 10 mg/m(3), 6 h/day for 4 consecutive days or 10 mg/m(3), 6 h/day, 1 day/week for 4 or 16 consecutive weeks). Two days following the last EPM exposure, cardiac and pulmonary tissues were examined histologically. The results showed that particle-laden alveolar macrophages were the only pulmonary lesions observed in all three rat strains. However, WKY rats exposed to EPM (10 mg/m(3) 6 h/day, 1 day/week for 16 weeks) demonstrated cardiac lesions with inflammation and degeneration. To further characterize the nature of EPM-associated lesions, more rigorous histopathological and histochemical techniques were employed for WKY and SD rats. We examined the hearts for myocardial degeneration, inflammation, fibrosis, calcium deposits, apoptosis, and the presence of mast cells. Decreased numbers of granulated mast cells, and multifocal myocardial degeneration, chronic-active inflammation, and fibrosis were present in 5 of 6 WKY rats exposed to EPM for 16 weeks. None of these lesions were present in WKY exposed to clean air. EPM-related cardiac lesions were indistinguishable from air-exposed controls in SD and SH rats. This study demonstrates that long-term inhalation exposures to environmentally relevant PM containing bioavailable zinc can cause myocardial injury in sensitive rats. These findings provide supportive evidence for the epidemiological associations of cardiovascular morbidity and ambient PM.

Experimental Studies in Animals

“…Some of these effects are observed even at low, near -ambient levels of PM, supporting the hypothesis that PM induces cardiac effects; however, the mechanisms remain poorly defi ned. We have shown that episodic subchronic but not shorter pulmonary exposure to residual oil fl y ash PM for 16 weeks increased myocardial cell damage and focal fi brosis and infl ammation in Wistar Kyoto rats (Kodavanti et al, 2003 ). Our studies have further reported cardiac molecular changes in gene expression following acute one -time high concentrations of zinc exposure, refl ecting a direct effect on the heart .…”

Morphologic Aspects of Rodent Cardiotoxicity in a Retrospective Evaluation of National Toxicology Program Studies

“…A statement released by the American Heart Association (Brook et al 2004), based on an extensive review of available evidence, concluded that exposure to particulate matter air pollution can contribute to an increased risk of acute fatality from cardiovascular events in humans. Moreover, it has recently been reported that inhalation exposure of Wistar Kyoto rats to particulate matter containing zinc resulted in myocardial degeneration (Kodavanti et al 2003). In a series of chronic studies of dioxins and dioxin-like compounds conducted by the National Toxicology Program (NTP) in female Sprague-Dawley rats, increased incidences of cardiomyopathy were observed in rats exposed to 2,3,7,, or the dioxinlike compound 3,3 0 4,4 0 ,5-pentachlorobiphenyl (PCB 126) (Jokinen et al 2003).…”

Efeitos cardiopulmonares da exposição ao material particulado fino (MP2,5) proveniente do concentrador de partículas ambientais (CPA) na hipertrofia ventricular esquerda de ratos wistar

“…Estas diferenças podem portando significar que não há necessariamente uma similaridade nos desfechos, e que o valor prognóstico da VFC que é demonstrado em diversas patologias humanas, ainda é prematuro para uso em roedores como um indicador de prognostico negativo ou toxicidade após exposições a poluentes ambientais (Rowan III et al, 2007). Conforme apontado por Kodavanti et al (2003) os estudos experimentais que avaliam os efeitos da exposição ao MP de origem veicular baseiam se principalmente em achados fisiológicos, muito pouco se avaliou quanto a histopatologia e bioquímica do tecido cardíaco e além disso há uma grande variabilidade quanto aos métodos e duração da exposição, composição do MP utilizado e espaço de tempo entre as exposições e avaliação dos desfechos (Vincent et al, 1997;Watkinson et al, 1998;Campen et al, 2001;Wellenius et al, 2002) dificultando comparações.…”