Nonparticulate Components of Diesel Exhaust Promote Constriction in Coronary Arteries from ApoE−/− Mice

Abstract

Air pollution is positively associated with increased daily incidence of myocardial infarction and cardiovascular mortality. We hypothesize that air pollutants, primarily vapor phase organic compounds, cause an enhancement of coronary vascular constriction. Such events may predispose susceptible individuals to anginal symptoms and/or exacerbation of infarction. To develop this hypothesis, we studied the effects of nonparticulate diesel exhaust constituents on (1) electrocardiographic traces from ApoE-/- mice exposed whole-body and (2) isolated, pressurized septal coronary arteries from ApoE-/- mice. ApoE-/- mice were implanted with radiotelemetry devices to assess electrocardiogram (ECG) waveforms continuously throughout exposures (6 h/day x 3 days) to diesel exhaust (0.5 and 3.6 mg/m3) in whole-body inhalation chambers with or without particulates filtered. Significant bradycardia and T-wave depression were observed, regardless of the presence of particulates. Pulmonary inflammation was present only in the whole exhaust-exposed animals at the highest concentration. Fresh diesel exhaust or air was bubbled through the physiologic saline tissue bath prior to experiments to enable the isolated tissue exposure; exposed saline contained elevated levels of several volatile carbonyls and alkanes, but low to absent levels of polycyclic aromatic hydrocarbons. Vessels were then assayed for constrictive and dilatory function. Diesel components enhanced the vasoconstrictive effects of endothelin-1 and reduced the dilatory response to sodium nitroprusside. These data demonstrate that nonparticulate compounds in whole diesel exhaust elicit ECG changes consistent with myocardial ischemia. Furthermore, the volatile organic compounds in the vapor phase caused enhanced constriction and reduced dilatation in isolated coronary arteries caused by nonparticulate components of diesel exhaust.

Health Effects of Fine Particulate Air Pollution: Lines that Connect

“…Dominici et al 47 indicate that the city-specific maximum likelihood estimates from the 88 largest U.S. cities range from Ϫ8% to ϩ8% (with a combined estimate of 0.4%) for a 20-g/m 3 PM 10 increment. In Katsouyanni et al, 48 the range was also wide, from Ϫ1.6% to ϩ2.7% per 20 g/m 3 of PM 10 . The pros and cons of combining such disparate results need to be considered.…”

“…The data in Table 5 of the review regarding cardiovascular admissions are subject to all of the uncertainties discussed above for PM and mortality. For example, the 14 individual city NMMAPS estimates 73 range from Ϫ2% to ϩ4.6% per 20-g/m 3 increase in PM 10 , which is a biologically implausible range.…”

“…As the literature from both animal 10 and human 11 studies of the relative effects of PM and non-PM components of combustion emissions grows, it increasingly reveals evidence for the causality of the non-PM fraction. Parsing the effects of components of complex mixtures is all the more, difficult because multiple components can have similar effects.…”

The World Trade Center disaster: a tragic source of medical advancement

“…In addition, a toxic plume containing metals, soot, volatile organic compounds and hydrochloric acid remained in the atmosphere for several days [13,14]. Many of these substances have been implicated in one or more pathways of vascular inflammation in experimental models, corroborating the hypothesis that irritant exposures may damage pulmonary vessels [15][16][17]. Compared to Lower Manhattan residents, passers-by and building occupants, the firefighters in this study were probably the ones subject to the highest exposures to these contaminants, from many hours of working in the pile of debris at ground zero.…”

Toxicidade cardiovascular e inflamatória aguda induzida pela inalação de partículas dos combustíveis diesel e biodiesel

“…Estudos recentes demonstraram que através da instilação intratraqueal aguda do PM 2,5 em ratos Wistar, na dose de 100 µg/mL e 500 µg/mL (Rivero et al, 2005a) e na dose de 50 µg/mL (Maatz et al, 2009) Em contrapartida, a literatura apresenta inúmeros estudos experimentais de toxicidade da queima do diesel (Campen et al, 2005;Anselme et al, 2007;Gottipolu et al, 2009;Saxena et al, 2009;Sunil et al, 2009) e de exposição controlada em humanos Lucking et al, 2008;Peretz et al, 2008aPeretz et al, , 2008bLangrish et al, 2009 Lucking et al, 2008;Langrish et al, 2009), a reatividade vascular (Peretz et al, 2008a) e a VFC (Peretz et al, 2008b). O compostos orgânicos da queima do diesel, são descritos como geradores de inflamação e estresse oxidativo (Ball et al, 2000;Saldiva et al, 2002;Nemmar et al, 2009;Sunil et al, 2009 Outros estudos também demonstraram que o B100 reduz as emissões de MP, CO e HC e aumenta as emissões de NO X (parâmetro não avaliado neste estudo) (EPA, 2002a;Graboski et al, 2003;Zou et al, 2003;Yuan et al, 2007;Lapuerta et al, 2008a).…”