Institute of Toxicology, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstädter Landstrasse 1, D-85764 Neuherberg, Germany.
ACS Nano. 2011 Jul 26;5(7):5345-53. doi: 10.1021/nn200801c. Epub 2011 Jun 7.
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.
工程纳米粒子(ENPs)在工业产品、食品和药物中的应用越来越多。ENPs 使用后的命运及其对健康的影响知之甚少。特别是作为空气污染物,悬浮的纳米粒子引起了一些关注,导致肺部和心血管系统疾病。人类健康风险可能源于吸入与炎症、体内分散和易受伤害的器官(如心脏、大脑)和组织暴露相关的毒性的 ENPs。然而,其潜在机制在很大程度上尚不清楚。此外,ENPs 在治疗应用中的未来使用正在研究中。因此,由于暴露于 ENPs 而导致的潜在心血管风险的知识需求量很大,但目前还没有建立既定的生物学测试模型。因此,我们建立了分离的跳动心脏(Langendorff 心脏)作为研究 ENPs 心血管效应的模型系统。该模型能够在 4 小时的最小时间段内观察和分析电生理参数,而不受全身效应的影响,并允许在 ENPs 影响下确定受刺激的物质释放。我们发现,由火焰烟尘(Printex 90)、火花放电生成的烟尘、锐钛矿(TiO2)和二氧化硅(SiO2)制成的 ENPs 显著增加了心率,并伴有心律失常。然而,火焰衍生的 SiO2(Aerosil)和单分散聚苯乙烯晶格没有表现出任何影响。心率的增加归因于心脏内肾上腺素能神经末梢释放儿茶酚胺。我们提出分离的 Langendorff 心脏及其电生理特性作为研究心血管 ENP 毒性的合适测试模型。