Heart rate variability (HRV) is a measure of cardiac pacing dynamics that has recently garnered a great deal of interest in environmental health studies. While the use of these measures has become popular, much uncertainty remains in the interpretation of results, both in terms of human and animal research. In humans, HRV endpoints, specifically chronic alterations in baseline HRV patterns, have been reasonably well characterized as prognostic indicators of adverse outcomes for a variety of diseases. However, such information is lacking for reversible HRV changes that may be induced by short-term exposures to environmental toxicants. Furthermore, there are minimal substantive data, either acute or chronic, regarding the pathological interpretation or prognostic value of toxicant-induced changes in HRV in rodents. The present report summarizes the physiological and clinical aspects of HRV, the methodological processes for obtaining these endpoints, and previous human and animal studies in the field of environmental health. Furthermore, we include a discussion of important caveats and recommendations for the interpretation of HRV data in animal research.

Epidemiological studies have reported statistically significant associations between the levels of ambient particulate matter (PM) and the incidence of morbidity and mortality, particularly among persons with cardiopulmonary disease. While similar effects have been demonstrated in animals, the mechanism(s) by which these effects are mediated are unresolved. To further investigate this phenomenon, the cardiovascular and thermoregulatory effects of an oil combustion-derived PM (HP-12) were examined in spontaneously hypertensive (SH) rats. The particle used in this study had considerably fewer water-soluble metals than the residual oil fly ash (ROFA) particles widely used in previous animal toxicity studies, with Zn and Ni constituting the primary water-leachable elements in HP-12. Rats were surgically implanted with radiotelemeters capable of continuously monitoring electrocardiogram (ECG), heart rate (HR), systemic arterial blood pressure (BP), and core temperature (T(co)). Animals were divided into four dose groups and were administered one of four doses of HP-12 suspended in saline vehicle (0.00, 0.83, 3.33, 8.33 mg/kg; control, low, mid, and high dose, respectively) via intratracheal instillation (IT). Telemetered rats were monitored continuously for up to 7 days post-IT, and were sacrificed 4 or 7 days post-IT. Exposures to mid- and high-dose HP-12 induced large decreases in HR (decreasing 30-120 bpm), BP (decreasing 20-30 mmHg), and T(co) (decreasing 1.2-2.6 degrees C). The decreases in HR and BP were most pronounced at night and did not return to pre-IT values until 72 and 48 h after dosing, respectively. ECG abnormalities (rhythm disturbances, bundle branch block) were observed primarily in the high-dose group. This study demonstrates substantial dose-related deficits in cardiac function in SH rats after IT exposure to a low-metal content, combustion-derived particle.

No abstract

A plethora of epidemiological studies have shown that exposure to elevated levels of ambient particulate matter (PM) can lead to adverse health outcomes, including cardiopulmonary-related mortality. Subsequent animal toxicological studies have attempted to mimic these cardiovascular and respiratory responses, in order to better understand underlying mechanisms. However, it is difficult to quantitate the amount of PM deposited in rodent lungs following inhalation exposure, thus making fundamental dose-to-effect assessment and linkages to human responses problematic. To address this need, spontaneously hypertensive rats were exposed to an oil combustion-derived PM (HP12) via inhalation while being maintained in whole-body plethysmograph chambers. Rats were exposed 6 h/day to 13 mg/m(3) of HP12 for 1 or 4 days. Immediately following the last exposure, rats were sacrificed and their tracheas and lung lobes harvested and separated for neutron activation analysis. Total lower respiratory tract deposition ranged from 20-60 microg to 89-139 microg for 1- and 4-day exposures, respectively. Deposition data were compared to default and rat-specific estimates provided by the Multiple Path Particle Deposition (MPPD) model, yielding model predictions that were < 33% of the measured dose. This study suggests that HP12 exposure decreased particle clearance, as the mass of HP12 in the lungs following a 4-day protocol was nearly four times that observed after a 1-day exposure. This work should improve the ability of risk assessors to extrapolate rat-to-human exposure concentrations on the basis of lung burdens and, thus, better relate inhaled doses and resultant toxicological effects.