A Cardiovascular Analysis of Post-exertional Malaise.

劳累后不适的心血管分析。

• 批准号: 10570877
• 负责人: DONNA M MANCINI
• 金额: $ 66.73万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-05-01 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10570877
• 关键词: Address; Affect; Age; Anaerobic Threshold; Attention; Behavioral; Blood Volume; Body mass index; Breathing; Cardiopulmonary; Cardiopulmonary Physiology; Cardiovascular system; Categories; Chronic Fatigue Syndrome; Clinical; Cognitive; Data; Exercise; Exercise Test; Exertion; Fatigue; Feeling; Gender; Goals; Hour; Hypovolemia; Hypovolemics; Infusion procedures; Intravenous; Isotonic Exercise; Link; Liquid substance; Malaise; Measures; Metabolic; Methods; Muscle; Noble Gases; Oxygen Consumption; Patients; Physiological; Physiology; Probability; Protocols documentation; Randomized; Reporting; Research; Research Personnel; Role; Saline; Severities; Severity of illness; Stroke Volume; Subgroup; Sweating; Symptoms; Testing; Time; Woman; Work; actigraphy; digital; disability; early onset; exhaustion; fitness; phenomenological models; prevent

Myalgic encephalomyelitis/chronic fatigue syndrome [CFS] is a disabling illness primarily affecting women. Post exertional malaise [PEM], thought to be the sine qua non of CFS, takes the form of a broad increase in symptoms occurring sometime after the cessation of often minimal exertion. Capturing and quantifying PEM remains problematic. Recent reports pointing to a possible metabolic deficit occurring on the second of two sequential cardiopulmonary exercise tests [CPET] done to exhaustion have attracted a great deal of attention for two reasons: as a metabolic manifestation of PEM and for use in proving patient disability. Specifically, the initial reports indicated that CFS patients failed to replicate their metabolic peak VO2 result on the second day of testing with an earlier onset of the anaerobic threshold defined as the oxygen consumption at the ventilatory threshold (VO2VT). Subsequent studies did not confirm the inability to replicate the peak VO2 on day #2 but did confirm the reduction in VO2VT from levels seen on day #1. However, we identified two problems with the work that has been done on 2-CPET testing: (1) the results are always presented as aggregate differences from day #1 to day #2 across different patients. Since CFS is defined clinically, it probably is comprised of multiple subgroups all with the same phenomenology but different pathophysiological causes. This would mean that only some – but not every – patient would show the abnormality in VO2VT on day #2 or severe PEM thereafter. (2) Although the researchers claim that this abnormality is a marker of PEM, there are no data linking patients who show this cardiopulmonary abnormality to the timing and severity of PEM. The overarching goal of this proposal is to overcome these deficiencies. A critical still unanswered question is why some CFS patients manifest VO2VT earlier on day #2 of CPET. We hypothesize that the reason for this is due to reduced total blood volume [TBV] leading to a reduced stroke volume [SV]. One of our early studies showed reduced SV in a subgroup of severely ill patients; later work from another group confirmed this finding, also in severely ill patients, and provided evidence to attribute this to reduced TBV. We hypothesize that exercise on day #1 will lead to insensible fluid loss related to sweating and deep rapid breathing which will further exacerbate thatthese changes will lead to decreases in reductions in TBV and SV. Accordingly, we hypothesize VO 2VTon day #2 CPET and that these decreases may be prevented by fluid expansion. We will evaluate these hypotheses by stratifying CFS on severity of symptoms, by determining TBV before each CPET, by measuring stroke volume during exercise using an inert gas rebreathing method, and by replenishing circulating volume intravenously for half the subjects shown to have reduced blood volume before day #2 testing. Finally we will determine how these changes relate to PEM. We will study 80 CFS patients [40 in the Severe and 40 in the Non-Severe categories] and compare the data from them to 40 matched healthy controls to address four aims to answer these research questions.

肌力脑脊髓炎/慢性疲劳综合征[CFS]是一种致命的疾病，主要影响女性。 劳累后[PEM]，被认为是CFS的正弦原则，以广泛增加的形式 症状在停止经常减少后发生。捕获和量化PEM 仍然有问题。最近的报告表明，在两个 顺序肺运动测试[CPET]疲惫吸引了很多关注 有两个原因：作为PEM的代谢表现，用于提供患者残疾。具体来说， 初步报告表明，CFS患者未能在第二天复制其代谢峰值。 用厌氧阈值开始的测试，定义为通风时的氧气消耗量 阈值（VO2VT）。随后的研究没有确认无法在第2天复制VO2的峰值，但确实如此 确认VO2VT从第1天看到的水平减少。 但是，我们确定了在2-CPET测试上完成的工作的两个问题：（1）结果是 从不同的患者开始，从第一天到第2天的总差异始终表示为总体差异。由于CFS是 在临床上定义，它可能由多个具有相同现象学但不同的亚组组成 病理生理原因。这意味着只有一些（但不是每个人）的患者才能显示 在第2天的VO2VT异常或此后的严重PEM。 （2）尽管研究人员声称这是 绝对是PEM的标记，没有链接患者的数据显示这种心肺绝对 PEM的时间和严重性。该提案的总体目标是克服这些缺陷。 一个关键的仍未解决的问题是，为什么有些CFS患者在CPET的第2天早些时候表现出VO2VT。我们 假设这样做的原因是由于总血量减少[TBV]导致中风减少 卷[SV]。我们的早期研究表明，严重患者的子组中的SV减少了。以后的工作 另一组也证实了这一发现，也是在严重患者中，并提供了证据将其归因于 减少了TBV。我们假设第1天的练习将导致与出汗和 呼吸深刻的呼吸，这将进一步加剧 这些变化将会 带领 到 减少 在 TBV和SV的减少。因此，我们假设 VO 2Vton Day＃2 CPET，这些下降可能是 由液体扩张阻止。我们将通过对症状严重程度进行分层CF来评估这些假设， 通过在每个CPET之前确定TBV，通过使用惰性气体在运动过程中测量中风量 重新呼吸方法，并通过对所显示的一半的受试者进行静脉注射循环体积 第2天测试前的血量减少。最后，我们将确定这些变化与PEM的关系。 我们将研究80名CFS患者[重度中的40例，在非重生类别中40例]，并比较数据 从他们到40个匹配的健康控件，以解决四个目标，以回答这些研究问题。