A Model-Based Estimate of Carbon Monoxide Uptake by Heart Muscle During Exercise

基于模型的运动过程中心肌吸收一氧化碳的估计

基本信息

批准号：
7254910
负责人：
EUGENE N BRUCE
金额：
$ 6.46万
依托单位：
UNIVERSITY OF KENTUCKY
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-07-01 至 2010-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7254910
关键词：
Model Based Estimate Carbon Monoxide

项目摘要

DESCRIPTION (provided by applicant): Intermittent exposures to carbon monoxide (CO) concentrations that exceed permissible levels are thought to contribute to the increased incidence of cardiovascular disease in exposed workers. A valid assessment of the cardiac risk associated with these exposures has proved difficult, in part because of limited information regarding the degree of hypoxia that occurs in heart tissue during these exposures. Although the Coburn-Forster-Kane Equation (CFKE) is often used to predict CO uptake by, and removal from, hemoglobin (Hb), it can not estimate CO uptake by extravascular tissues such as muscle, a potentially large storage site for CO as muscle accounts for approximately 41% of body weight in young, adult males. Therefore, we developed, and validated with human data, a mathematical model of CO uptake and washout that, unlike the CFKE, includes a muscle compartment. Our model predicts that the CO concentration in muscle increases soon after the onset of the exposure and rises steadily as carboxyhemoblobin (COHb) increases. When used to assess CO washout under hyperoxia, the common treatment strategy for toxic CO exposures, our model predicts a further rise in CO uptake by muscle myoglobin (Mb), even as COHb levels fall, suggesting an increased risk for hypoxic injury to the myocardium. Based on these results, we hypothesize that a mathematical model that could predict COMb levels in cardiac muscle would provide a more accurate estimate of risk for cardiac hypoxia than COHb alone. Accordingly, the objectives of this proposal are to use data sets obtained from two human CO exposure experiments to: 1) enhance our model to enable it to predict COHb and COMb during exercise and washout under hyperoxia, and 2) evaluate the correlation between the predicted CO dose to the heart and subtle ECG changes during exercise and washout under hyperoxia. To accomplish these objectives we will expand the model to include a separate myocardial compartment, optimize our method for fitting the model and estimating myocardial COMb at rest and during exercise in each subject, and correlate model estimates of myocardial COMb levels with degree of cardiac electrical instability. Relevance: To understand the increased risk for heart disease in workers exposed to carbon monoxide, we will use our mathematical model to analyze existing data from exposed humans to determine the exposure conditions likely to damage the heart. We will also determine whether treatment with 100% oxygen may be harmful in some cases.

描述（由申请人提供）：超过允许水平的一氧化碳（CO）浓度的间歇性暴露被认为有助于暴露的工人中心血管疾病的发病率增加。事实证明，对与这些暴露相关的心脏风险进行有效评估很困难，部分原因是关于这些暴露期间心脏组织中缺氧程度的信息有限。尽管Coburn-Forster-Kane方程（CFKE）通常用于预测血红蛋白（HB）的CO摄取和去除，但它无法估计血管外组织（如肌肉）（如肌肉）的摄取，这是肌肉的潜在较大的储藏点，这是CO作为肌肉的可能性大的肌肉，肌肉占年轻的成人，成人，成人的成人大约41％。因此，我们通过人类数据开发并验证了CO摄取和清除的数学模型，与CFKE不同，它包括一个肌肉舱。我们的模型预测，肌肉的CO浓度在暴露发作后不久会增加，并且随着羧基杂霉素（COHB）的增加而稳步上升。当用于评估高氧下的CO冲洗时，毒性CO暴露的常见治疗策略，我们的模型预测肌肉肌红蛋白（MB）的CO进一步增加，即使COHB水平下降，也表明对心肌造成低氧损伤的风险增加。基于这些结果，我们假设一个可以预测心脏肌肉中梳子水平的数学模型将为心脏缺氧的风险提供更准确的估计，而不是单独使用COHB。因此，该提案的目标是使用从两个人类CO暴露实验获得的数据集，以：1）增强我们的模型，使其能够预测cohb和梳子在锻炼和梳理过程中，以及2）评估预测的co剂量与心脏的相关性，并在运动过程中进行锻炼，并在多氧下进行洗涤。为了实现这些目标，我们将扩展模型以包括一个单独的心肌室，优化我们的模型拟合方法，并在每个受试者进行运动过程中估算心肌梳子，并将心肌梳子水平的模型估计与心脏电气不稳定程度相关联。相关性：了解暴露于一氧化碳的工人中心脏病的风险增加，我们将使用我们的数学模型来分析来自暴露的人类的现有数据，以确定可能损害心脏的暴露状况。我们还将确定在某些情况下使用100％氧的治疗是否可能有害。