title: Cardiovascular responses in unrestrained WKY rats to inhaled ultrafine carbon particles.
abstract: Based on epidemiologic observations, the issue of adverse health effects of inhaled ultrafine particles (UFP) is currently under intensive discussion. We therefore examined cardiovascular effects of UFP in a controlled animal exposure on young, healthy WKY rats. Short-term exposure (24 h) to carbon UFPs (38 nm, 180 microg m (-3)), generated by spark discharging, induced a mild but consistent increase in heart rate (18 bpm, 4.8%), which was associated with a significant decrease in heart-rate variability during particle inhalation. The timing and the transient character of these responses point to a particle induced alteration of cardiac autonomic balance, mediated by a pulmonary receptor activation. After 24 h of inhalation exposure, bronchoalveolar lavage revealed significant but low-grade pulmonary inflammation (clean air 1.9% vs. UFPs 6.9% polymorphonuclear cells) and on histopathology sporadic accumulation of particle-laden macrophages was found in the alveolar region. There was no evidence of an inflammation-mediated increase in blood coagulability, as UFP inhalation did not induce any significant changes in plasma fibrinogen or factor VIIa levels and there were no prothrombotic changes in the lung or the heart at both the protein and mRNA level. Histological analysis revealed no signs of cardiac inflammation or cardiomyopathy. This study therefore provides toxicological evidence for UFP-associated pulmonary and cardiac effects in healthy rats. Our findings suggest that the observed changes are mediated by an altered sympatho-vagal balance in response to UFP inhalation, but do not support the concept of an inflammation-mediated prothrombotic state by UFP.
authors.affiliation: Institute for Inhalation Biology GSF-National Research Center for Environment and Health, Neuherberg, Germany. harder@gsf.de
authors.forename: Volker
authors.initials: V
authors.lastname: Harder
authors.forename: Peter
authors.initials: P
authors.lastname: Gilmour
authors.forename: Bernd
authors.initials: B
authors.lastname: Lentner
authors.forename: Erwin
authors.initials: E
authors.lastname: Karg
authors.forename: Shinji
authors.initials: S
authors.lastname: Takenaka
authors.forename: Axel
authors.initials: A
authors.lastname: Ziesenis
authors.forename: Andreas
authors.initials: A
authors.lastname: Stampfl
authors.forename: Urmila
authors.initials: U
authors.lastname: Kodavanti
authors.forename: Joachim
authors.initials: J
authors.lastname: Heyder
authors.forename: Holger
authors.initials: H
authors.lastname: Schulz
mesh_terms: D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D002244:Carbon / Q000633:toxicity*; D002318:Cardiovascular Diseases / Q000209:etiology* / Q000662:veterinary; D006339:Heart Rate / Q000187:drug effects*; D007249:Inflammation; D019570:Inhalation Exposure; D008168:Lung / Q000276:immunology* / Q000473:pathology; D008264:Macrophages; D008297:Male; D010316:Particle Size; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000393:Air Pollutants; D002244:Carbon