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）：关于心血管发病率和死亡率，空气污染是一个重要的公共卫生问题。在理解所涉及的神经和心脏机制方面已经取得了重要成长。心率变异性分析表明，在暴露于浓缩空气颗粒（CAP）的过程中，自主语调的重要干扰。我们已经在犬类模型中获得了证据，表明帽子可能会增加急性冠状动脉阻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，旨在扩大我们对心血管系统空气颗粒机制的理解。具体目的是：1）确定环境空气颗粒对使用CAP暴露的有意识狗中冠状动脉血流动力功能和动脉血压的影响。 2）确定环境空气颗粒对冠状动脉血流和抗药性的影响是否会因使用CAP暴露的有意识狗的冠状动脉狭窄加剧。我们的研究将继续采用哈佛环境颗粒浓度（HAPC），该设备可以将周围颗粒浓度提高到30倍而不会改变颗粒的物理或化学特征。 2）典型的城市气溶胶； 3）疾病的动物模型，包括狗中的心肌缺血，以模拟患有缺血性心脏病的人的病情，这是成人心脏死亡率的主要基质。这些动物将用流量探针和遥测装置长期仪器，以监测动脉血压和EKG。在正常犬和部分冠状动脉狭窄的狗中，将监测冠状动脉流动和压力，并在交感神经或副交感神经阻滞期间进行比较。在调节冠状动脉血管反应期间，将评估由内皮蛋白控制和一氧化氮控制的血管活性平衡。污染物成分的影响将被系统地研究。因此，当前的应用将需要采用全面技术的独特应用，以提高对机制的理解，使帽子可以对其对心脏和循环的有害影响产生有害的影响