Environmental Engineering Reference
In-Depth Information
metal homeostasis was induced by the instilled Zn sulfate. Further evidence
suggested disruption of essential metal homeostasis, with the induction of MT-1 and
ZT-2 in the heart, lung and liver. Zn exposure was signifi cantly associated with
changes in genes affecting calcium homeostasis, mitochondrial activity, cell-
signaling pathways, ion channels and transferases. These results suggest a possible
direct mechanism and effect of pulmonary Zn exposure on cardiac tissue
in vivo
.
Gilmour et al. (
2006
) evaluated the relationship between pulmonary exposure to
Zn and potential direct and indirect cardiovascular responses by instilling 2
mol/
kg of Zn sulfate or saline (time matched control) in male Wistar Kyoto rats (same
dose described in Gilmour et al.
2006
). Rats were examined 1, 4, 24 and 48 h post
exposure for responses in blood chemistry, BALF, histopathology and gene expres-
sion. Circulating levels of Zn increased by 20% above baseline at 1-24 h post-
exposure. Signifi cant lung injury/infl ammation occurred at 1-24 h intervals
post-exposure as evidenced by analyses of BALF and histopathology. Moreover, the
level of injury/infl ammation produced was severe and could indirectly induce car-
diac impairment. Gene expression in both lung and cardiac tissue following Zn
exposure was signifi cantly increased for tissue factor (TF) and plasminogen
activator-inhibitor-1 (PAI-1), in exposed vs. time-matched control rats, which may
lead to increased coagulation and thrombosis. There was extensive pulmonary
injury/infl ammation, whereas only mild focal cardiovascular lesions were observed
with no histological evidence of increased fi brin. However, at 24 and 48 h, blood
levels of fi brinogen were signifi cantly increased. The authors suggested that impair-
ments in blood coagulation (pro-coagulative effects), in combination with pulmo-
nary injury induced by Zn exposure may be a potential mechanism for adverse
cardiovascular responses to Zn in ambient PM.
Muggenburg et al. (
2003
) measured electrocardiographic responses to inhalation
exposure to single metal oxides (viz., the relatively insoluble oxides of Cu, Fe, Mn,
Ni, or V) or single metal sulfates (viz., soluble oxides of Ni or V). Older dogs (n = 8)
that had naturally occurring cardiovascular defi ciencies were exposed to 0.05 mg/
m
3
(a concentration of Ni roughly 10,000 times higher than found in ambient PM)
of single metal aerosols or fi ltered air for 3 h on 3 successive days. All particles were
respirable and had a mass median aerodynamic diameter range of 0.72-2.93
ʼ
m.
ECGs were continuously recorded throughout each exposure period and were ana-
lyzed for changes in heart rate, heart rate variability and abnormal wave forms. No
signifi cant effects of exposure were observed for any aerosol containing a single
metal oxide or sulfate (Table
9
). In a parallel qualitative study, in which ECG trends
were visually analyzed without statistical analyses, no effects were observed in
dogs (n = 4) exposed to high concentrations of ROFA (Muggenburg et al.
2003
). The
lack of associations in this study (Muggenburg et al.
2003
) could result from: 1) not
evaluating the effect of metal mixtures or the presence of co-pollutants in ambient
PM, 2) the study size being too small (n = 4 per group) and, thus, lacking power to
detect signifi cant effect differences (no power analysis was reported by the authors),
and 3) the length and frequency of exposure were too short. More frequent or longer
duration exposures may be required to elicit effects.
ʼ
Search WWH ::
Custom Search