Noninvasive Quantification of the Resistance Baroreflex

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。测量TPR压力反射的传统技术旨在量化压力反射系统的开环增益值。虽然多元回归分析（MRA）可以确定这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干扰，因此很少受到关注。因此，TPR压力反射系统的整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清楚地量化，只有在自然发生的，心跳到心跳的血流动力学变化的信息。虽然这种微妙的变化一直是过去许多压力反射研究的焦点，但尚未专门用于TPR压力反射的表征。我们已经开发了一种数学算法来量化每个TPR压力感受器反射的闭环增益值，通过分析只有心跳到心跳的测量ABP和心输出量（CO）。我们已经证明了算法的可行性，在一个单一的动物，并在一小组的人，其中ABP和CO进行非侵入性测量。我们建议在慢性动物研究中进一步开发和严格评估该算法。具体目标1是验证由数学算法确定的TPR压力反射增益值。我们将研究多达15只清醒的房室传导阻滞犬，并进行心脏起搏和ABP、CO和中心静脉压（CVP）的测量。该实验准备将使我们能够将通过将算法应用于AV顺序起搏期间测量的ABP和CO而确定的TPR压力感受器反射增益值与通过将MRA应用于在一组心室率和血容量调整期间测量的ABP、CVP和CO而建立的参考值进行比较。具体目标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。我们将在给予改变压力反射功能的药物后重复上述方案。这些特定目标的成功实现可能最终导致一种实用的技术，该技术通常用于促进对人类和动物健康和疾病中TPR压力感受器反射的基本理解。

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.