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.

肌痛性脑脊髓炎/慢性疲劳综合征 [CFS] 是一种主要影响女性的致残性疾病。 劳累后不适 [PEM] 被认为是慢性疲劳综合症 (CFS) 的必要条件，其表现为 通常是在停止轻微运动后一段时间出现的症状。捕获和量化 PEM 仍然存在问题。最近的报告指出，两次中的第二次可能发生代谢缺陷 进行至力竭的连续心肺运动试验[CPET]引起了广泛关注 原因有两个：作为 PEM 的代谢表现以及用于证明患者残疾。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摄氧量结果 早期出现无氧阈值（定义为通气时的耗氧量）的测试 阈值（VO2VT）。随后的研究并未证实无法复制第 2 天的峰值摄氧量，但确实如此 确认 VO2VT 较第一天的水平有所降低。 然而，我们发现 2-CPET 测试工作存在两个问题：(1) 结果是 始终呈现为不同患者从第 1 天到第 2 天的总体差异。由于 CFS 是 根据临床定义，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——但不是所有——患者会表现出 第 2 天 VO2VT 异常或此后严重 PEM。 (2) 尽管研究人员声称这 异常是 PEM 的标志，没有数据关联显示这种心肺异常的患者 PEM 的时间和严重程度。该提案的总体目标是克服这些缺陷。 一个尚未解答的关键问题是为什么一些 CFS 患者在 CPET 第 2 天较早地表现出 VO2VT。我们 假设其原因是总血容量 [TBV] 减少导致中风减少 体积[SV]。我们的一项早期研究表明，重病患者亚组的 SV 降低；以后的工作 另一组研究人员也在重症患者中证实了这一发现，并提供了证据将其归因于 减少TBV。我们假设第一天的锻炼会导致与出汗和相关的不明显的液体流失 深呼吸急促，这会进一步加剧 这些变化将 带领 到 减少 在 TBV 和 SV 减少。据此，我们假设 VO 2VTon 第 2 天 CPET，这些下降可能是 被流体膨胀所阻止。我们将通过根据症状严重程度对 CFS 进行分层来评估这些假设， 通过在每次 CPET 之前确定 TBV，通过使用惰性气体测量运动期间的每搏输出量 再呼吸方法，并通过静脉补充循环容量，为一半的受试者提供了 在第 2 天测试之前减少血容量。最后我们将确定这些变化与 PEM 有何关系。 我们将研究 80 名 CFS 患者（40 名重度患者和 40 名非重度患者）并比较数据 从他们到 40 个匹配的健康对照，以解决回答这些研究问题的四个目标。