Background: Epidemiological studies have shown an association between ambient particulate matter (PM) and morbidity (hospital admissions) and mortality from cardiovascular disease. These studies support the premise that increases in the concentration of fine particles, and to a lesser extent NOx, SOx, and CO, are associated with cardiovascular effects. The specific cardiovascular conditions exacerbated by air pollution events are uncertain, but ischemic heart disease and arrhythmias are likely candidates.

The components of PM associated with the cardiovascular effects are uncertain. The major constituents of PM are sulfate, nitrate, organic and elemental carbon, ammonium ions, and a variety of trace metals. The metal composition of the particles varies depending on the emission source, but includes the reactive transition metals vanadium, chromium, nickel, manganese, and copper. Previous animal studies focusing on the effects of residual oil fly ash (ROFA) or concentrated ambient air particles on cardiac function have produced variable results. Some dogs have shown changes in the PR segments, ST segments and the T wave form of the electrogardiogram (ECG), and changes in heart rate during inhalation of ROFA. Studies of rats instilled intratracheally with ROFA have demonstrated heart arrhythmias and a few deaths.

Goals and Experimental Design: This study is testing the hypothesis that specific transition metals cause ECG abnormalities in dogs when inhaled. The exposures will be much more extreme than experienced in the environment, as a first order evaluation of whether high concentrations of pure aerosols of relative insoluble (oxide) and soluble (sulfate) metal particles cause measurable effects. The study also served to explore exposure and measurement techniques and the dog model for potential inclusion in the NERC core studies.

Four healthy aged dogs, two males and two females aged 12-13 years (termed the "normal" group) were exposed for 3 hours on 3 consecutive days to aerosols of Ni, V, Cu, Fe, and Mn as oxides, and to Ni and V as sulfates, all at a concentration of 50 µg/m3. The dogs breathed the aerosols orally via mouth tubes while standing in slings with only light restraint. ECG's were recorded continuously using several standard leads and a chest lead. The ECG's were be examined for heart rate, heart-rate variability, arrhythmias, and changes in the various segments of the ECG complexes, such as elevated ST segment or T alterans.

Using the same exposure system and recording procedures, four dogs, three males and one female, having significant systolic murmurs over the mitral valves (termed the "abnormal" group) were exposed to aerosols of Ni and V as sulfates. Two of these dogs had clinical signs of early congestive heart failure. The other two dogs were considered to be in a pre-heart failure state. These dogs ranged in age from 6 to 17 years old. One of these dogs, a male, was part of the original four aged dogs described above. That dog was exposed twice to the Ni and V sulfate aerosols.

Status: The exposures and data collection have been completed. The particle size distribution of the exposure aerosol was measured using cascade impactors, and the results are presented in Table 6.

With one exception, all of the dogs were able to complete the exposures as planned. One male dog in the normal group was removed from the second day of exposure to Cu oxide after 2 hours because of cardiopulmonary arrest. This apparently occurred because the dog's mouth piece and breathing tube became inadvertently occluded. The dog was resuscitated and successfully completed all of the remaining exposures.

Detailed evaluations of the ECG's are now underway. Observations of the ECG's during exposure indicated that most of the normal group exhibited the sinus arrhythmia that is typical of healthy dogs. Escape complexes and some supraventricular beats were observed among these dogs during all exposures, and further data analysis will be required to determine whether the incidence of these events was related to exposure. The abnormal group had abnormal ECG traces and did not exhibit sinus arrhythmia. There were marked differences among the dogs in some measures of heart rate variability, but further data analysis will be required to determine if these differences were related to exposure. Data analysis should be completed by August 2000.