A Cardiovascular Analysis of Post-exertional Malaise.

劳累后不适的心血管分析。

• 批准号: 10211169
• 负责人: DONNA M MANCINI
• 金额: $ 68.28万
• 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/10211169
• 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; Infusion procedures; Intravenous; Isotonic Exercise; Link; Liquid substance; Malaise; Measures; Metabolic; Methods; Muscle; Noble Gases; Oxygen Consumption; Patients; Physiological; Physiology; Protocols documentation; Randomized; Reporting; Research; Research Personnel; Role; Saline; Severities; Severity of illness; Short Interspersed Nucleotide Elements; Stroke Volume; Subgroup; Sweating; Symptoms; Testing; 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.

肌痛性脑脊髓炎/慢性疲劳综合征是一种主要影响妇女的致残性疾病。 劳累后不适[PEM]，被认为是CFS的必要条件，采取的形式是广泛增加 在通常是最小的运动停止后出现的症状。捕获和量化PEM 仍然存在问题。最近的报告指出，可能的代谢缺陷发生在第二个两个 连续心肺运动试验[CPET]已经引起了人们的极大关注 原因有两个：作为PEM的代谢表现和用于证明患者残疾。具体而言是 最初的报告表明，CFS患者在第二天未能复制其代谢峰值VO 2结果 无氧阈值定义为呼吸室的耗氧量， 阈值（VO 2 VT）。随后的研究未证实无法复制第2天的峰值VO 2，但证实 确认VO 2 VT较第1天观察到的水平降低。 然而，我们发现了2-CPET测试工作中的两个问题：（1）结果是 始终表示为不同患者从第1天到第2天的总差异。由于CFS是 在临床上定义，它可能由多个亚组组成，所有亚组具有相同的现象学，但不同 病理生理原因。这意味着只有一些-但不是所有-患者会表现出 第2天VO 2 VT异常或此后重度PEM。(2)尽管研究人员声称， 异常是PEM的标志物，没有数据将显示这种心肺异常的患者联系起来 PEM的时间和严重程度本提案的首要目标是克服这些缺陷。 一个关键的尚未回答的问题是为什么一些CFS患者在CPET的第2天更早地表现出VO 2 VT。我们 假设其原因是由于总血量[TBV]减少导致中风减少 体积[SV]。我们的一项早期研究显示，重症患者亚组的SV减少; 另一组的研究证实了这一发现，也是在重症患者中，并提供了证据将其归因于 降低TBV。我们假设第1天的运动会导致与出汗有关的无感觉液体丢失， 深呼吸急促，这将进一步加剧 这些变化将 铅 到 减小 在 降低TBV和SV。因此，我们假设 第2天CPET的VO 2 VT，这些降低可能是 防止液体膨胀。我们将通过对CFS症状的严重程度进行分层来评估这些假设， 通过在每次CPET之前确定TBV，通过在使用惰性气体的运动期间测量每搏输出量， 再呼吸方法，并通过静脉补充循环容量的一半的受试者显示， 在第2天测试前减少血容量。最后，我们将确定这些变化与PEM的关系。 我们将研究80例CFS患者[40例重度和40例非重度类别]并比较数据 从他们到40个匹配的健康对照组，以解决四个目标来回答这些研究问题。