Cardiac and Thermoregulatory Effects of Instilled Particulate Matter-Associated Transition Metals in Healthy and Cardiopulmonary-Compromised Rats

Campen, Matthew J.; Nolan, Julianne P.; Schladweiler, Mette C.; Kodavanti, Urmila P.; Costa, Daniel L.; Watkinson, William P.

doi:10.1080/00984100290071694

Cited by 68 publications

(40 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…These findings have been discovered in parallel with compelling evidence that lethal arrhythmias are likely caused by a shift in autonomic balance towards sympathetic domination [15]. It has been further shown that rodents exposed to a number of toxicants or stressors [29][30][31][32][33][34] can experience rapid changes in cardiac function, suggesting a role for the neural reflexes of the ANS [33]. The results from these various studies have contributed to the growing interest in measuring HRV in environmental toxicology research.…”

Section: Introductionmentioning

confidence: 88%

Heart rate variability in rodents: uses and caveats in toxicological studies

et al. 2007

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Section: Introductionmentioning

confidence: 88%

Heart rate variability in rodents: uses and caveats in toxicological studies

et al. 2007

Self Cite

View full text Add to dashboard Cite

show abstract

“…Although the issue of dose imparts uncertainty in the interpretation of the effects seen in experimental animals, the coherence in the effects seen in animals with model and ambient PM lends credence to its use to explore mechanistic questions surrounding rare effects seen in the exposed human population (Costa and Dreher 1997;Dye et al 2001). The inflammatory responses to the IT dose of ROFA used in this study have been well characterized in healthy and compromised animal models and have been compared with INH of comparable doses of the metal sulfates themselves (Campen et al 2002). The estimated cumulative dose of ROFA resulting from the INH exposure based on 15% deposition was 3.03 mg/kg.…”

Section: Discussionmentioning

confidence: 99%

Emission-particle-induced ventilatory abnormalities in a rat model of pulmonary hypertension.

Gardner

McGee

Kodavanti

et al. 2004

Environ Health Perspect

View full text Add to dashboard Cite

Preexistent cardiopulmonary disease in humans appears to enhance susceptibility to the adverse effects of ambient particulate matter. Previous studies in this laboratory have demonstrated enhanced inflammation and mortality after intratracheal instillation (IT) and inhalation (INH) of residual oil fly ash (ROFA) in a rat model of pulmonary hypertension induced by monocrotaline (MCT). The present study was conducted to examine the effects of ROFA in this model on ventilatory function in unanesthetized, unrestrained animals. Sixty-day-old male CD rats were injected with MCT (60 mg/kg) or vehicle (VEH) intraperitoneally 10 days before IT of ROFA (8.3 mg/kg) or saline (SAL) (control) or nose-only INH of ROFA [15 mg/m3 for 6 hr on 3 consecutive days or air (control)]. At 24 and 72 hr after exposure, rats were studied individually in a simultaneous gas uptake/whole-body plethysmograph. Lungs were removed at 72 hr for histology. Pulmonary test results showed that tidal volume (VT) decreased 24 hr after IT of ROFA in MCT-treated rats. Breathing frequency, minute volume (VE), and the ventilatory equivalent for oxygen increased in MCT- and VEH-treated rats 24 hr after IT or INH of ROFA and remained elevated 72 hr post-IT. O2 uptake (VO2) decreased after IT of ROFA in MCT-treated rats. Carbon monoxide uptake decreased 24 hr after IT of ROFA, returning to control values in VEH-treated rats but remaining low in MCT-treated rats 72 hr post-IT. ROFA exposure induced histologic changes and abnormalities in several ventilatory parameters, many of which were enhanced by MCT treatment.

show abstract

“…Both Zn and V modulate the function of cardiac myocytes by slowing their spontaneous beat rate, analogous to slowing of heart rate previously demonstrated in rats instilled with residual oil fly ash containing high amounts these metals (Campen et al 2002;Wichers et al 2004). However, compared with V, the decrease induced by Zn was significantly more pronounced and occurred at lower concentrations with shorter exposure times.…”

Section: Discussionmentioning

confidence: 99%

Metal Particulate Matter Components Affect Gene Expression and Beat Frequency of Neonatal Rat Ventricular Myocytes

Graff¹,

Cascio²,

Brackhan³

et al. 2004

Environ. Health Perspect.

View full text Add to dashboard Cite

Soluble particulate matter (PM) components (e.g., metals) have the potential to be absorbed into the bloodstream and transported to the heart where they might induce the expression of inflammatory cytokines and remodel electrical properties. We exposed cultured rat ventricular myocytes to similar concentrations of two metals [zinc (Zn) and vanadium (V)] found commonly in PM and measured changes in spontaneous beat rate. We found statistically significant reductions in spontaneous beat rate after both short-term (4-hr) and long-term (24-hr) exposures, with a more substantial effect seen with Zn. We also measured the expression of genes associated with inflammation and a number of sarcolemmal proteins associated with electrical impulse conduction. Exposure to Zn or V (6.25-50 µM) for 6 hr produced significant increases in IL-6, IL-1α, heat shock protein 70, and connexin 43 (Cx43). After 24 hr exposure, Zn induced significant changes in the gene expression of Kv4.2 and KvLQt (potassium channel proteins), the α 1 subunit of the L-type calcium channel, and Cx43, as well as IL-6 and IL-1α. In contrast, V produced a greater effect on Cx43 and affected only one ion channel (KvLQT1). These results show that exposure of rat cardiac myocytes to noncytotoxic concentrations of Zn and V alter spontaneous beat rate as well as the expression of ion channels and sarcolemmal proteins relevant to electrical remodeling and slowing of spontaneous beat rate, with Zn producing a more profound effect. As such, these data suggest that the cardiac effects of PM are largely determined by the relative metal composition of particles.

show abstract

Cardiac and Thermoregulatory Effects of Instilled Particulate Matter-Associated Transition Metals in Healthy and Cardiopulmonary-Compromised Rats

Cited by 68 publications

References 34 publications

Heart rate variability in rodents: uses and caveats in toxicological studies

Heart rate variability in rodents: uses and caveats in toxicological studies

Emission-particle-induced ventilatory abnormalities in a rat model of pulmonary hypertension.

Metal Particulate Matter Components Affect Gene Expression and Beat Frequency of Neonatal Rat Ventricular Myocytes

Contact Info

Product

Resources

About