 |
||
|
National Center For Environmental Research |  |
 |
||
|
|
||||||
|
|
|
|||||||||||||||
|
|
Presentation AbstractAir Pollutants: Cardiovascular Effects and MechanismsAnn Bonham, Chao-Yin Chen, Barbara Horwitz, Kent Pinkerton, Michael
Kleeman, EPA Grant Number: RD831918 Project Description: Epidemiological studies link exposure to airborne particulates with
mass aerodynamic diameter
|
|||||
|
|
|
|
||
|
|
2.5
µm (PM2.5) and cardiovascular consequences including
ventricular arrhythmias and sudden cardiac death. The causes are poorly
understood, but reduced heart rate variability (HRV) is particularly compelling
since it is an index of impaired cardiac vagal regulation and is associated
with increased susceptibility to ventricular arrhythmias and sudden death.
Moreover, the elderly appear to be particularly susceptible. The challenge
is to link the epidemiological findings to causes and mechanisms. Toward
that end, we propose to test three hypotheses: (1) that exposure (3, 7,
14, and 28 days) to ambient air pollutants reduces HRV by causing neuroplasticity
in the intrinsic or synaptic excitability of cardiac vagal neurons in
the nucleus ambiguus (NA) which control HRV; (2) that the decreased HRV
and mechanisms are different in summer vs. winter due to season-dependent
particulate composition; and (3) that the decreased HRV and mechanisms
are exaggerated in the elderly. We will test the hypotheses by five objectives,
using state-of-the-art inhalation facilities to deliver environmentally
relevant and comprehensively characterized “real world” particulate
pollutants in the form of concentrated ambient air particles (CAPs) of
the PM2.5 fraction to a mouse model shown to exhibit reduced
HRV in response to indoor air PM2.5 exposure. Mice of median
age 3-4 months (age equivalent to young adult humans) and of 26-28 months
(age equivalent to elderly humans) will be exposed to one of the following:
CAPs PM2.5 in summer (when motor vehicle exhaust contributes
43% and wood smoke contributes 1% to total PM2.5); filtered
air (FA) as a summer control group; CAPs PM2.5 in winter (when
vehicle exhaust contributes 22 % and wood smoke 21%) and FA as a winter
control group. Mice will be studied after 3, 7, 24, and 28 days exposures.
Objective 1 will determine if PM2.5 exposure reduces HRV, by
quantifying overall 24-h HRV, diurnal changes in HRV, and heart rate recovery
following an acute stressor (exercise) in conscious, freely moving mice.
Objectives 2 and 3 will use patch clamping to determine if the PM2.5
exposure-induced decrease in HRV is mediated by decreased intrinsic
excitability of NA cardiac vagal neurons through changes in specific
potassium channel conductances. Objectives 4 and 5 will determine if the
PM2.5 exposure-induced decrease in HRV is mediated by decreased
synaptic excitability via enhanced inhibitory (l-aminobutyric acid)
and/or reduced excitatory (glutamatergic) mechanisms. The results should
provide a model and mechanisms for cardiovascular consequences to air
pollution and should improve public awareness of PM2.5.