Cardiac vulnerability due to ambient particulate

环境颗粒物导致心脏脆弱

• 批准号: 7095144
• 负责人: John J Godleski
• 金额: $ 58.13万
• 依托单位: HARVARD SCHOOL OF PUBLIC HEALTH
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-30 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7095144
• 关键词: air pollution; artery stenosis; blood pressure; cardiovascular function; dogs; electrocardiography; endothelin; hemodynamics; myocardial ischemia /hypoxia; nitric oxide; parasympathetic nervous system; telemetry; vasoactive agent

DESCRIPTION (provided by applicant): Particulate air pollution is an important public health problem with respect to cardiovascular morbidity and mortality. Important strides have been made in understanding the neural and cardiac mechanisms involved. Heart rate variability analysis revealed important disturbances in autonomic tone during exposure to concentrated air particles (CAPs). We have obtained evidence in our canine models that CAPs may increase the severity of ischemia during acute coronary artery occlusion. These findings provide the direction for our studies, which are intended to expand our understanding of the mechanisms of air particulate exposure on the cardiovascular system. The specific aims are: 1) To determine the effect of ambient air particles on coronary hemodynamic function and arterial blood pressure in conscious dogs using CAPs exposures. 2) To determine whether the influence of ambient air particles on coronary artery blood flow and resistance is exacerbated by coronary artery stenosis in conscious dogs using CAPs exposures. Our studies will continue to employ the Harvard Ambient Particulate Concentrator (HAPC), a device that can increase ambient particle concentrations up to 30x without changing the physical or chemical characteristics of the particles; 2) a typical urban aerosol; 3) animal models of disease including myocardial ischemia in dogs to simulate the condition of compromised humans with ischemic heart disease, the primary substrate for adult cardiac mortality. The animals will be chronically instrumented with flow probes and telemetry devices to monitor arterial blood pressure and EKG. Coronary blood flow and pressure will be monitored in normal dogs and in dogs with partial coronary artery stenosis and compared during sympathetic or parasympathetic nerve blockade. The vasoactive balance controlled by endothelins and nitric oxide will be assessed during regulation of the coronary vascular response. The effects of components of pollutants will be systematically studied. Thus, the present application will entail unique application of comprehensive techniques to improve understanding of the mechanisms whereby CAPs can exert its deleterious influences on the heart and circulation

描述（由申请人提供）：空气颗粒物污染是一个与心血管发病率和死亡率有关的重要公共卫生问题。在理解所涉及的神经和心脏机制方面已经取得了重要进展。心率变异性分析揭示了暴露于浓缩空气颗粒（CAP）期间自主神经张力的重要紊乱。我们在犬模型中获得的证据表明，CAP 可能会增加急性冠状动脉闭塞期间缺血的严重程度。这些发现为我们的研究提供了方向，旨在扩大我们对空气颗粒暴露对心血管系统影响机制的理解。具体目标是： 1) 使用 CAP 暴露来确定环境空气颗粒对清醒狗冠状动脉血流动力学功能和动脉血压的影响。 2) 使用 CAP 暴露来确定清醒狗的冠状动脉狭窄是否会加剧环境空气颗粒对冠状动脉血流和阻力的影响。我们的研究将继续采用哈佛环境颗粒物浓缩器（HAPC），该设备可以将环境颗粒物浓度提高高达 30 倍，而不会改变颗粒物的物理或化学特性； 2）典型的城市气溶胶； 3）疾病动物模型，包括狗的心肌缺血，以模拟患有缺血性心脏病的受损人类的状况，缺血性心脏病是成人心脏死亡的主要基础。这些动物将长期配备流量探头和遥测设备来监测动脉血压和心电图。将监测正常狗和冠状动脉部分狭窄的狗的冠状动脉血流量和压力，并在交感神经或副交感神经阻滞期间进行比较。在调节冠状血管反应期间将评估由内皮素和一氧化氮控制的血管活性平衡。将系统地研究污染物成分的影响。因此，本申请将需要综合技术的独特应用，以增进对 CAP 对心脏和循环产生有害影响的机制的理解