Cardiovascular and thermoregulatory effects of inhaled PM-associated transition metals: A potential interaction between nickel and vanadium sulfate

Recent epidemiological studies have shown an association between daily morb idity and mortality and ambient particulate matter (PM) air pollution. It h as been proposed that bioavailable metal constituents of PM are responsible for many of the reported adverse health effects. Studies of instilled resi dual oil fly ash (ROFA) demonstrated immediate and delayed responses, consi sting of bradycardia, hypothermia, and arrhythmogenesis in conscious, unres trained rats. Further investigation of instilled ROFA-associated transition metals showed that vanadium (V) induced the immediate responses, while nic kel (Ni) was responsible for the delayed effects. Furthermore, Ni potentiat ed the immediate effects caused by V when administered concomitantly. The p resent study examined the responses to these metals in a whole-body inhalat ion exposure. To ensure valid dosimetric comparisons with instillation stud ies, 4 target exposure concentrations ranging from 0.3-2.4 mg/m(3) were use d to incorporate estimates of total inhalation dose derived using different ventilatory parameters. Rats were implanted with radiotelemetry transmitte rs to continuously acquire heart rate (HR), core temperature (T-CO), and el ectrocardiographic data throughout the exposure. Animals were exposed to ae rosolized Ni, V, or Ni + V for 6 h per day x 4 days, after which serum and bronchoalveolar lavage samples were taken. Even at the highest concentratio n, V failed to induce any significant change in HR or T-CO. Ni caused delay ed bradycardia, hypothermia, and arrhythmogenesis at concentrations > 1.2 m g/m(3). When combined, Ni and V produced observable delayed effects at 0.5 mg/m(3) and potentiated responses at 1.3 mg/m(3), greater than were produce d by the highest concentration of Ni (2.1 mg/m(3)) alone. These results ind icate a possible synergistic relationship between inhaled Ni and V, and pro vide insight into potential interactions regarding the toxicity of PM-assoc iated metals.