van de Luit L, van der Meulen J, Cleophas T J, Zwinderman A H
Department of Medicine, Merwede Hospital Dordrecht, The Netherlands.
Angiology. 1998 Nov;49(11):903-8. doi: 10.1177/000331979804901105.
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.
疲劳是昼夜节律紊乱的一个重要症状。迄今为止，尚未发表过关于慢性疲劳综合征（CFS）患者昼夜节律的研究。本研究的目的是研究慢性疲劳综合征患者与年龄匹配的血压正常对照组相比的心率、收缩压和舒张压节律，并研究褪黑素和异搏帕明对这些节律的影响。根据1987年美国疾病控制中心标准，对18例慢性疲劳综合征患者进行了动态血压（ABP）测量（Space Lab公司产品，经验证），并将12例年龄匹配的血压正常对照组的测量结果用于两组的余弦分析。随后，在一项为期8周的开放标签评估中，对4例患者研究了褪黑素和异搏帕明对ABP的影响。有1例患者为高血压患者（每4小时至少有一次舒张压>90mmHg），因此被排除。其余17例患者（15例女性，2例男性）的数据显示，心率有显著的12小时节律，收缩压和舒张压有24小时节律，其95%置信区间与正弦模式无显著差异。虽然这些节律与对照组的节律同步，但其幅度不同，分别为对照组节律幅度的2.8倍、2.8倍和9.0倍（分别为p<0.001、p<0.001和p<0.0001）。慢性疲劳综合征患者夜间收缩压持续低于100mmHg。在随后一项针对该研究人群中4例患者的初步研究中，这些患者每天服用4mg褪黑素和200mg异搏帕明，持续4周，结果显示异搏帕明减轻了夜间低血压（p<0.05），而褪黑素加重了夜间低血压（p<0.02）。慢性疲劳综合征患者昼夜节律幅度增加，夜间收缩压持续低于100mmHg。正性肌力化合物可能对这类患者有益，但褪黑素可能并非如此。
