title: Langendorff heart: a model system to study cardiovascular effects of engineered nanoparticles.
abstract: Engineered nanoparticles (ENPs) are produced and used in increasing quantities for industrial products, food, and drugs. The fate of ENPs after usage and impact on health is less known. Especially as air pollution, suspended nanoparticles have raised some attention, causing diseases of the lung and cardiovascular system. Human health risks may arise from inhalation of ENPs with associated inflammation, dispersion in the body, and exposure of vulnerable organs (e.g., heart, brain) and tissues with associated toxicity. However, underlying mechanisms are largely unknown. Furthermore future use of ENPs in therapeutic applications is being researched. Therefore knowledge about potential cardiovascular risks due to exposure to ENPs is highly demanded, but there are no established biological testing models yet. Therefore, we established the isolated beating heart (Langendorff heart) as a model system to study cardiovascular effects of ENPs. This model enables observation and analysis of electrophysiological parameters over a minimal time period of 4 h without influence by systemic effects and allows the determination of stimulated release of substances under influence of ENPs. We found a significant dose and material dependent increase in heart rate accompanied by arrhythmia evoked by ENPs made of flame soot (Printex 90), spark discharge generated soot, anatas (TiO(2)), and silicon dioxide (SiO(2)). However, flame derived SiO(2) (Aerosil) and monodisperse polystyrene lattices exhibited no effects. The increase in heart rate is assigned to catecholamine release from adrenergic nerve endings within the heart. We propose the isolated Langendorff heart and its electrophysiological characterization as a suitable test model for studying cardiovascular ENP toxicity.
authors.affiliation: Institute of Toxicology, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstädter Landstrasse 1, D-85764 Neuherberg, Germany. stampfl@helmholtz-muenchen.de
authors.forename: Andreas
authors.initials: A
authors.lastname: Stampfl
authors.forename: Melanie
authors.initials: M
authors.lastname: Maier
authors.forename: Roman
authors.initials: R
authors.lastname: Radykewicz
authors.forename: Peter
authors.initials: P
authors.lastname: Reitmeir
authors.forename: Martin
authors.initials: M
authors.lastname: Göttlicher
authors.forename: Reinhard
authors.initials: R
authors.lastname: Niessner
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002395:Catecholamines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography / Q000187:drug effects; D004738:Engineering; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D053758:Nanoparticles / Q000009:adverse effects*
chemical_list: D002395:Catecholamines; D002118:Calcium