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Arnold Peckerman, Ph.D., Benjamin H. Natelson, M.D.,
John J. LaManca, Ph.D.,
Claudia Pollet, M.D., Sharon L. Smith, B.S., and John Ottenweller, Ph.D.
East Orange DVA Medical Center
Introduction. Severe chronic fatigue is one of the
most common and disabling health problems among veterans of the Gulf War
(GVs). This study tested a hypothesis that centrally-originating abnormalities
in sympathetic control of circulation contribute to symptoms in GVs with
chronic fatigue syndrome (CFS). The study also examined for alterations
in immune functioning in GVs with CFS as a possible factor in autonomic
dysregulation.
Procedures. The study sample consisted of 35 VA Gulf
War Registry veterans who met CDC criteria for CFS and 34 healthy Registry
veterans. Cardiovascular sympathetic function was examined as hemodynamic
responses to the cold pressor test, and two cognitive challenges, an evaluative
speech task and mental arithmetic. Response measurements included blood
pressure (BP), and impedance cardiography-derived stroke volume (SV),
cardiac output (Q), total peripheral resistance (TPR), and Heather Index
of myocardial contractility (HI). Immune measures included enumeration
of monocytes, granulocytes, lymphocyte subsets, and concentration of cytokines
(IL-2, IL-4, IL-6, IL10, IL-12, interferon-?, and TNF-a) in plasma.
Results. During behavioral stress testing, GVs with
CFS displayed greatly attenuated BP responses to speech (p<.0001) and
mental calculations (p<.005). In contrast, no differences in responses
were observed during the cold pressor test. Diminished BP responses to
cognitive stressors in veterans with CFS were associated with a lower
SV, Q, and HI values, and increased TPR (ps<.05), indicating a low
flow circulatory state. Significantly, within the CFS group, fatigue severity
was predictive of low blood pressure responses to cognitive stressors
(R2=.20, p<.008). On measures of immune function, veterans with CFS
had higher monocytes and neutrophils counts (ps<.05), and lower NK
(p<.05) and higher T-helper cell subsets (p<.005). This pattern
of changes in immune cells in Gvs with CFS was associated with increased
concentration of IL-2, IL-4, IL-10, and TNF-a cytokines. Stepwise multiple
regression analyses examined the relationship between these indicators
of immune activation and cardiovascular hypofunction. A combination of
higher monocyte and TNF-a levels was predictive of low BP responses to
cognitive stressors (R2=.43, p<.0001). Lower resting Q was associated
with lower TNF-a levels, and hanges in Q during cognitive tasks were negatively
related to IL-10 levels (ps<.05).
Conclusions. The diminished blood pressure responsiveness
to cognitive but not sensory stress in GVs with CFS is consistent with
a hypothesis that a central nervous system disorder involving integration
between higher cortical brain functioning and sympathetic control of circulation
may be the underlying pathology in these veterans. Low flow circulatory
pattern displayed by GVs with CFS suggests a mechanism through which autonomic
dysregulation may become expressed as symptoms of CFS. This study also
indicates that in part, autonomic dysregulation in GVs with CFS may be
related to immune activation, involving proliferation of monocytes and
their cytokine products, including TNF-a, as well as an increased activity
of Th2 cytokines, notably IL-10. Further research extending these findings
into the specific mechanisms of the observed cardiac hypofunction and
its relation to immune factors holds considerable promise for future clinical
interventions.
Keywords: Chronic Fatigue Syndrome, Cardiac Output, Stress
Reactivity
This work was supported by DVA Medical Research Funds and
DVA NJCEHR |
