# A Cardiovascular Analysis of Post-exertional Malaise.

> **NIH NIH R01** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2021 · $682,769

## Abstract

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 ...

## Key facts

- **NIH application ID:** 10211169
- **Project number:** 1R01NS117638-01A1
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** DONNA M MANCINI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $682,769
- **Award type:** 1
- **Project period:** 2021-05-01 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10211169

## Citation

> US National Institutes of Health, RePORTER application 10211169, A Cardiovascular Analysis of Post-exertional Malaise. (1R01NS117638-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10211169. Licensed CC0.

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