Amplified amplitudes of circadian rhythms and nighttime hypotension in patients with chronic fatigue syndrome: improvement by inopamil but not by melatonin

Abstract:

Fatigue is an important symptom of a disturbed circadian rhythm. To date, no studies of circadian rhythms in patients with chronic fatigue syndrome (CFS) have been published.

The objectives of the study were to study rhythms of heart rate and systolic and diastolic blood pressure in patients with chronic fatigue syndrome compared with age-matched normotensive controls and to study the effects of melatonin and inopamil on such rhythms.

Ambulatory blood pressure (ABP) measurements (Space Lab, Inc, validated) of 18 patients with CFS were made according to the 1987 U.S. Center for Disease Control Criteria, and measurements of 12 age-matched normotensive controls were used in a cosinor analysis of the two groups. The effects of melatonin and inopamil on ABP were studied subsequently in four patients in an 8-week open-label evaluation. One patient was hypertensive (diastolic blood pressure > 90 mm Hg at least once every 4 hours), and was, therefore, excluded.

The data of the remaining 17 patients (15 women, 2 men) revealed a significant 12-hour rhythm in heart rate and 24-hour rhythm in systolic and diastolic blood pressure with 95% confidence intervals not significantly different from sinusoidal patterns. Although these rhythms were synchronous with the control group rhythms, their amplitudes were not and showed, respectively, 2.8, 2.8, and 9.0 times the size of the control group rhythms (p < 0.001, p < 0.001, and p < 0.0001, respectively). Systolic blood pressures in the patients with CFS were consistently below 100 mm Hg during the nighttime.

In a subsequent pilot study of four patients from the study population treated with melatonin 4 mg daily and inopamil 200 mg daily for 4 weeks, inopamil reduced nighttime hypotension (p < 0.05), whereas melatonin increased nighttime hypotension (p < 0.02).

Patients with CFS have increased amplitudes of circadian rhythms and systolic blood pressures consistently below 100 mm Hg during the nighttime. Positive inotropic compounds may be beneficial in such patients, but melatonin may not be.

 

Source: van de Luit L, van der Meulen J, Cleophas TJ, Zwinderman AH. Amplified amplitudes of circadian rhythms and nighttime hypotension in patients with chronic fatigue syndrome: improvement by inopamil but not by melatonin. Angiology. 1998 Nov;49(11):903-8. http://www.ncbi.nlm.nih.gov/pubmed/9822046

 

Dissociation of body-temperature and melatonin secretion circadian rhythms in patients with chronic fatigue syndrome

Abstract:

Many patients with chronic fatigue syndrome (CFS) display features of hypothalamic dysfunction. We have investigated aspects of circadian rhythmicity, an important hypothalamic function, in 20 CFS patients and in 17 age- and sex-matched healthy control subjects.

There were no differences between the two groups in the amplitude, mesor (mean value) or timing of the peak (acrophase) of the circadian rhythm of core temperature, or in the timing of the onset of melatonin secretion.

However, the CFS patients showed no significant correlation between the timing of the temperature acrophase and the melatonin onset (P < 0.5), whereas the normal significant correlation was observed in the controls (P < 0.05). Dissociation of circadian rhythms could be due to the sleep deprivation and social disruption, and/or the reduction in physical activity which typically accompany CFS.

By analogy with jet-lag and shift-working, circadian dysrhythmia could be an important factor in initiating and perpetuating the cardinal symptoms of CFS, notably tiredness, impaired concentration and intellectual impairment.

 

Source: Williams G, Pirmohamed J, Minors D, Waterhouse J, Buchan I, Arendt J, Edwards RH. Dissociation of body-temperature and melatonin secretion circadian rhythms in patients with chronic fatigue syndrome. Clin Physiol. 1996 Jul;16(4):327-37. http://www.ncbi.nlm.nih.gov/pubmed/8842569