Noninvasive Quantification of the Resistance Baroeflex

描述(由申请人提供)：动脉和心肺压力反射系统对总外周阻力(TPR)的反馈控制是动脉血压(ABP)调节的重要机制。传统的测量TPR压力反射的技术旨在量化一个压力反射系统的开环增益值。虽然多元回归分析(MRA)可以确定两个系统的闭环增益值，但这种分析要求进行复杂的实验准备，其中心率和血容量都受到扰动，因此很少受到关注。因此，两个TPR压力反射系统的综合功能仍然知之甚少。我们的假设是，这两个TPR压力感受器反射系统可以仅根据自然发生的、搏动到搏动的血流动力学变化中存在的信息来明确地量化。虽然这种微妙的变化在过去一直是许多压力反射研究的焦点，但还没有专门用于描述TPR压力反射的特征。我们开发了一种数学算法来量化每个TPR压力反射的闭环增益值，方法是只分析每一次动脉压和心输出量(CO)的逐次测量。我们已经在单个动物和一小群人身上证明了该算法的可行性，在这些人中，ABP和CO是非侵入性测量的。我们建议在慢性动物研究中进一步发展和严格评估该算法。具体目标1是验证由数学算法确定的TPR压力反射增益值。我们将研究15只有房室传导阻滞的清醒犬，用仪器测量心脏起搏和测量ABP、CO和中心静脉压(CVP)。这项实验准备将使我们能够将通过将算法应用于房室顺序起搏期间测量的ABP和CO而确定的TPR压力反射增益值与通过对一系列心室率和血容量调整期间测量的ABP、CVP和CO应用MRA而建立的参考值进行比较。具体目的2是证明由数学算法确定的TPR压力反射增益值在各种压力反射状态下是有效的。在给予改变压力感受器反射功能的药物后，我们将重复上述方案。这些特定目标的成功实现可能最终导致一种实用的技术，这种技术通常被用来促进对人和动物在健康和疾病方面的TPR压力反射的基本了解。

DESCRIPTION (provided by applicant): Feedback control of total peripheral resistance (TPR) by the arterial and cardiopulmonary baroreflex systems is an important mechanism for arterial blood pressure (ABP) regulation. Traditional techniques for measuring the TPR baroreflex aim to quantify the open-loop gain value of one baroreflex system. While multiple regression analysis (MRA) can determine the closed-loop gain values of both systems, this analysis mandates a sophisticated experimental preparation in which both heart rate and blood volume are perturbed and has therefore received little attention. Thus, the integrated functioning of both TPR baroreflex systems remains poorly understood. Our hypothesis is that both TPR baroreflex systems may be distinctly quantified from only the information present in naturally occurring, beat-to-beat hemodynamic variations. While this subtle variability has been the focus of many baroreflex studies in the past, it has not been exploited specifically for the characterization of the TPR baroreflex. We have developed a mathematical algorithm to quantify the closed-loop gain values of each TPR baroreflex by analyzing only beat-to-beat measurements of ABP and cardiac output (CO). We have demonstrated the feasibility of the algorithm in a single animal and in a small set of humans in which ABP and CO were noninvasively measured. We propose further development and rigorous evaluation of the algorithm in chronic animal studies. Specific Aim 1 is to validate the TPR baroreflex gain values determined by the mathematical algorithm. We will study up to15 conscious dogs with atrio-ventricular (AV) block and instrumented for cardiac pacing and measurement of ABP, CO, and central venous pressure (CVP). This experimental preparation will allow us to compare the TPR baroreflex gain values determined by applying the algorithm to ABP and CO measured during AV sequential pacing with reference values established by applying MRA to ABP, CVP, and CO measured during a set of adjustments to ventricular rate and blood volume. Specific Aim 2 is to demonstrate that the TPR baroreflex gain values determined by the mathematical algorithm are valid under various baroreflex states. We will repeat the above protocol after the administration of drugs that alter baroreflex functioning. Successful achievement of these specific aims may ultimately lead to a practical technique that is routinely employed to advance the basic understanding of the TPR baroreflex in both humans and animals in health and disease.