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EFFECTS OF INSTILLED EMISSION PARTICULATE MATTER ON ELECTROCARDIOGRAPHIC INDICES AND HEART RATE VARIABILITY (HRV) IN SPONTANEOUSLY HYPERTENSIVE RATS
Citation:
Wichers, L. B., J. P. Nolan, W. H. Rowan, D L. Costa, W P. Watkinson, M. J. Campen, AND T. P. Jenkins. EFFECTS OF INSTILLED EMISSION PARTICULATE MATTER ON ELECTROCARDIOGRAPHIC INDICES AND HEART RATE VARIABILITY (HRV) IN SPONTANEOUSLY HYPERTENSIVE RATS. Presented at Society of Toxicology, Baltimore, MD, March 21-25, 2004.
Description:
EFFECTS OF INSTILLED EMISSION PARTICULATE MATTER (EPM) ON ELECTROCARDIOGRAPHIC INDICES AND HEART RATE VARIABILITY (HRV) IN SPONTANEOUSLY HYPERTENSIVE (SH) RATS. L.B. Wichers1, J.P. Nolan2, W.H. Rowan2, M.J. Campen3, T.P. Jenkins4, D.L. Costa2, and W.P. Watkinson2. 1UNC SPH, Chapel Hill, NC, USA; 2USEPA, ORD/NHEERL/ETD/PTB, RTP, NC, USA; 3LRRI, Albuquerque, NM, USA; 4ECU, Brody SOM, Greenville, NC, USA.
Epidemiological studies have linked increased levels of ambient particulate matter (PM) with increased morbidity and mortality, noting higher correlations in persons with cardiovascular disease. To further investigate this phenomenon, we examined the effects of EPM (an "ambient-like" emission particle) in SH rats (a susceptible disease model). Rats were implanted with radiotelemeters capable of monitoring electrocardiogram (ECG), heart rate (HR), blood pressure (BP), and core temperature (Tco). Animals (n=109) were divided into four groups and exposed via intratracheal instillation (IT) to suspensions of EPM (0.0, 0.83, 3.33, 8.33 mg/kg) in acidified saline vehicle. Telemetered rats were monitored continuously for 96h post-IT and ECG waveforms were acquired at 10-min intervals throughout the study. Ventilatory function was examined (Buxco Electronics) concurrently for 6h/day on postexposure Days 1-4 while subsets of rats underwent bronchoalveolar lavage (BAL) at 24h, 96h, and 192h post-IT. ECG abnormalities (rhythm disturbances, premature ventricular contractions) were observed primarily in the high dose group. Detailed analyses of ECG intervals and indices of HRV showed evidence of immediate (<2 hours) increases in HRV followed by a delayed (>2 days) return to control levels. Additionally, exposure to the higher doses of EPM induced dose-related decreases in HR, BP, and Tco, that persisted for up to 72h. Significant increases in BAL indices of pulmonary injury were also noted. These studies demonstrate substantial deficits in cardiopulmonary function in SH rats after IT exposure to EPM. The observed changes in cardiopulmonary function in moderately compromised rodents support the results of previous epidemiological studies and may implicate similar biologically-plausible mechanisms in humans.
(Abstract does not represent USEPA policy. This research was supported in part by EPA CT826513.)