A Cardiovascular Analysis of Post-exertional Malaise.

肌痛性脑脊髓炎/慢性疲劳综合征是一种主要影响女性的致残性疾病。 运动性后不适[PEM]，被认为是CFS的必要条件，其形式是 停止运动后出现的症状，通常是最小的运动停止后出现的症状。捕获和量化PEM 仍然是有问题的。最近的报告指出，两个人中的第二个可能出现代谢缺陷 连续的心肺运动试验[CPET]已经引起了人们的极大关注 有两个原因：作为PEM的代谢表现和用于证明患者残疾。具体地说， 初步报告表明，CFS患者在第二天未能复制他们的代谢高峰VO2结果 无氧阈值出现较早的测试，定义为呼吸机的耗氧量 阈值(VO2VT)。随后的研究没有证实无法复制第二天的VO2峰值，但确实如此 确认VO2VT较第一天的水平有所下降。 然而，我们在2-CPET测试中发现了两个问题：(1)结果是 总是表现为不同患者从第一天到第二天的总体差异。由于CFS是 从临床上来说，它可能由多个亚群组成，这些亚群都具有相同的现象学，但不同 病理生理原因。这将意味着只有一些-但不是每一个-患者会表现出 第2天VO2VT异常或其后出现严重的PEM。(2)尽管研究人员声称这一点 异常是PEM的一个标志，没有数据表明患者有这种心肺异常 PEM的时机和严重性。这项提案的首要目标是克服这些缺陷。 一个关键的仍未回答的问题是，为什么一些CFS患者在CPET第二天更早地表现出VO2VT。我们 假设出现这种情况的原因是由于总血量减少导致卒中减少 音量[SV]。我们早期的一项研究显示，一部分重症患者的SV降低；后来的工作 来自另一个小组的研究证实了这一发现，也是在重病患者中，并提供了证据将其归因于 降低了总体积。我们假设，第一天的锻炼会导致与出汗有关的无意识液体流失， 深而快速的呼吸会进一步加重 这些变化将 铅 至 减少 在……里面 TBV和SV的降低。因此，我们假设 VO 2VT第2天CPET，这些减少可能是 通过液体膨胀来阻止。我们将通过根据症状的严重程度对CFS进行分层来评估这些假设， 通过在每次CPET之前测量TBV，通过使用惰性气体测量运动期间的每搏输出量 重复呼吸法，并通过静脉补充循环容量为一半的受试者显示有 在第二天检测前减少了血容量。最后，我们将确定这些变化与PEM之间的关系。 我们将研究80名CFS患者[40名重症患者和40名非重症患者]，并对数据进行比较 从他们到40名匹配的健康对照组，解决了四个目标，以回答这些研究问题。

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.