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

• 批准号: 7016199
• 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
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-01 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7016199
• 关键词: carbon monoxide; carboxyhemoglobin; environmental exposure; exercise; human data; mathematical model; model design /development; myocardium; myoglobin; occupational hazard

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）：间歇性暴露于超过允许水平的一氧化碳 (CO) 浓度被认为会导致暴露工人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，部分原因是有关这些暴露期间心脏组织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) 吸收和去除的 CO2，但它无法估计肌肉等血管外组织吸收的 CO2，而肌肉是 CO2 潜在的大型储存场所，因为在年轻成年男性中，肌肉约占体重的 41%。因此，我们开发了一个二氧化碳吸收和冲刷的数学模型，并用人体数据进行了验证，与 CFKE 不同，该模型包括一个肌肉室。我们的模型预测，肌肉中的 CO 浓度在接触开始后很快就会增加，并随着碳氧血红蛋白 (COHb) 的增加而稳定上升。当用于评估高氧条件下的 CO 冲刷（有毒 CO 暴露的常见治疗策略）时，我们的模型预测即使 COHb 水平下降，肌肉肌红蛋白 (Mb) 吸收的 CO 也会进一步增加，这表明心肌缺氧损伤的风险增加。基于这些结果，我们假设能够预测心肌中 COMb 水平的数学模型将比单独的 COHb 更准确地估计心脏缺氧的风险。因此，本提案的目标是使用从两次人体 CO 暴露实验中获得的数据集来：1）增强我们的模型，使其能够预测高氧运动和冲刷过程中的 COHb 和 COMb，2）评估预测值之间的相关性在高氧条件下运动和冲洗期间，心脏的 CO 剂量和心电图的细微变化。为了实现这些目标，我们将扩展模型以包括单独的心肌室，优化我们的模型拟合方法以及估计每个受试者静息和运动期间心肌 COMb 的方法，并将心肌 COMb 水平的模型估计与心电不稳定程度相关联。相关性：为了了解接触一氧化碳的工人患心脏病的风险增加，我们将使用我们的数学模型来分析接触一氧化碳的人类的现有数据，以确定可能损害心脏的接触条件。我们还将确定在某些情况下使用 100% 氧气进行治疗是否可能有害。