The circadian variation of cardiovascular stress levels and reactivity: Relationships to individual differences in morningness/eveningness

Two studies assessed the circadian variation of cardiovascular responses to stress in healthy and coronary artery disease (CAD) populations. In within-subjects designs, stressors were administered to healthy male subjects and male CAD patients both in the morning and afternoon, and subjects were classified as either morning or evening types using the Morningness-Eveningness Questionnaire (Horne & Östberg, 1976, International Journal of Chronobiology, 4, 97–110). No consistent circadian variation in blood pressure or heart rate responses was observed in the aggregate sample of either healthy subjects or CAD patients. However, there were significant interactions between circadian type and time of day. In both populations, morning, subjects exhibited higher cardiovascular levels during the morning session, and evening subjects exhibited higher levels during the afternoon session. Analyses of cardiovascular reactivity revealed less consistent evidence for this interaction. Self-reports of stress revealed interactions between time of day and and morningness/eveningness only in CAD sample. In CAD patients, preliminary analysis of myocardial wall function, an index of myocardial ischemia, did not reveal a significant interaction between morningness/eveningness and time of day, perhaps due to small sample size. The presence of differing circadian patterns in stress response based on individual differences in morningness/eveningness is discussed in teerms of its methodological implications for psychophysiological research and in terms of the role of stress as an acute trigger of CAD.     

Circadian rhythms in arthritis: hormonal effects on the immune/inflammatory reaction

Biological signaling and rhythms occur in a complex network with participation and interaction of the central nervous system, the autonomic nervous system, the endocrine glands, peripheral endocrine tissues and the immune system. It is a clinical observation that patients affected by chronic immune/inflammatory conditions (i.e. rheumatoid arthritis/RA) exhibit circadian, circamensual (females) and circannual rhythms of disease-related symptoms. Proinflammatory cytokines exhibit a peculiar rhythmicity, in particular serum TNF and serum IL-6, and together with other relevant immunological parameters display an elevation in the early morning hours in patients with RA. As a matter of fact, RA patients particularly experience joint pain, morning stiffness, and functional disability in the early morning hours. Since circadian rhythmicity of neuroendocrine pathways is closely coupled to immune/inflammatory reactions, new aspects at least concerning RA management are suggested. In particular, further investigations will indicate whether timed release of immunosuppressive/antiinflammatory drugs will have increased efficacy and whether dosages can be reduced below critical levels above which adverse events appear.     

Self-reported diurnal mood changes, early morning awakening and the dexamethasone suppression test in endogenous depression

Several authors have suggested that Dexamethasone Suppression Test (DST) non-suppression is related to circadian alternations of hypothalamic-pituitary-adrenal function. Two clinical manifestations of altered circadian rhythms in depressed patients are early morning awakening and diurnal variation in mood. To observe whether these clinical symptom patterns were associated with an increased frequency of abnormal DSTs, we examined post-DST plasma cortisol concentrations and matched clinical ratings of early morning awakening and diurnal variation in mood in 49 patients with major depressive disorder, endogenous subtype. We found no significant association between these clinical and laboratory variables.     

71例阵发性房性心动过速的动态心电图分析与探讨

目的：探讨71例阵发性房性心动过速发生规律及其临床意义。方法 ：应用动态心电图对71例短阵房性心动过速发生规律及其昼夜节律进行监测与分析。结果：房性心动过速以冠心病发生率最高（49.3%）;检出率随年龄增长而增加,老年组检出率最高,尤以男性发生率增加更为明显,与其他年龄组比较差异有统计学意义（P〈0.01）;老年组房性心动过速昼夜节律减弱。结论：冠心病患者受到心房肌缺血、缺氧、炎症、变性、纤维化等多种因素的影响,使心房肌除极速度不一致,利于短阵房性心动过速的发生;短阵房性心动过速的检出率随年龄增长呈上升趋势,主要因素与心肌退行性病变引起心脏自律性、兴奋性及传导性发生改变有关;房性心动过速昼夜节律减弱,提示老年人房性心动过速多为病理性改变。     

Phase-shifting effects of bright morning light as treatment for delayed sleep phase syndrome

Bright light has recently been shown to have phase-shifting effects on human circadian rhythms. In this study we applied this effect to 20 patients with delayed sleep phase syndrome (DSPS) who were unable to fall asleep at conventional clock times and had a problem staying alert in the morning. In a controlled treatment study, we found that 2 h of bright light exposure in the morning together with light restriction in the evening successfully phase advanced circadian rhythms of core body temperature and multiple sleep latencies in these patients. This finding corroborates the importance of light for entraining human circadian rhythms.     

Maternal deprivation in neonatal rats alters the expression of circadian system under light-dark cycles and restricted daily feeding in adulthood

Effects of maternal deprivation (MD) with different conditions were examined on the circadian rhythms in plasma corticosterone and locomotor activity in adult rats under ad libitum and restricted daily feeding (RF), in which rats had free access to food for 2 h for 3 weeks. Three different types of MD were performed from postnatal day 1 (P1) to day 6 (P6); MD for 12 h/day (MD12), for 3 h/day in the morning (MD3am) and in the afternoon (MD3pm). Under ad libitum feeding, corticosterone levels at 08:00 h and 24:00 h were significantly increased in MD12 rats. A similar increase was detected in MD3am rats, but not in MD3pm rats. Under the RF, corticosterone levels at 08:00 h, 24:00 h, and 04:00 h were significantly increased in MD12 rats. Similar elevations were detected in MD3am rats, but not in MD3pm rats. Furthermore, prefeeding locomotor activities under the RF increased significantly in MD12 rats. A similar increase was observed in MD3am rats, but not in MD3pm rats. Keeping ambient temperature and humidity at 37 degrees C and 70-80% during MD attenuated the effects of MD on the corticosterone rhythmicities under RF as well as ad lib feeding. It is concluded that MD in the early postnatal period influences the expressions of circadian rhythms in plasma corticosterone and locomotor activity in adult rats. Not only the length but also the time of day of MD seems to be critical for these effects. Ambient temperature and/or humidity are suggested to be one of the factors by which MD exerts its effect.     

Increased light exposure consolidates sleep and strengthens circadian rhythms in severe Alzheimer's disease patients

Sleep in the nursing home environment is extremely fragmented, possibly in part as a result of decreased light exposure. This study examined the effect of light on sleep and circadian activity rhythms in patients with probable or possible Alzheimer's disease. Results showed that both morning and evening bright light resulted in more consolidated sleep at night, as measured with wrist actigraphy. Evening light also increased the quality of the circadian activity rhythm, as measured by a 5-parameter extended cosine model (amplitude, acrophase, nadir, slope of the curve, and relative width of the peak and trough). Increasing light exposure throughout the day and evening is likely to have the most beneficial effect on sleep and on circadian rhythms in patients with dementia. It would behoove nursing homes to consider increasing ambient light in multipurpose rooms where patients often spend much of their days.     

Circadian variation in vascular tone and its relation to alpha-sympathetic vasoconstrictor activity

BACKGROUND. The frequency of several cardiovascular events, such as myocardial infarction, sudden death, and stroke, is increased during the early morning hours. There is also a similar circadian pattern in several physiologic variables, including blood pressure, suggesting that certain dynamic processes may contribute to the circadian distribution and onset of acute events. METHODS. To determine whether there are circadian variations in vascular tone and to investigate their underlying mechanisms, we measured blood flow and vascular resistance in the forearm and their responses to phentolamine (an alpha-adrenergic-antagonist drug) and sodium nitroprusside (a direct vasodilator) in 12 normal subjects (7 men and 5 women; mean age [+/- SD], 44 +/- 9 years) at three different times of day (7 a.m., 2. p.m., and 9 p.m.). The drugs were infused into the brachial artery, and the responses were measured by strain-gauge plethysmography. RESULTS. The basal forearm vascular resistance was significantly higher, and the blood flow significantly lower, in the morning than in the afternoon and evening (mean vascular resistance, 31 +/- 8, 25 +/- 6, and 22 +/- 7 mm Hg per milliliter per minute per 100 ml of forearm volume, respectively; P less than 0.01). The vasodilator effect of phentolamine was also significantly greater in the morning (mean decrease in vascular resistance, 38 +/- 6 percent) than in the afternoon (26 +/- 6 percent) and evening (21 +/- 7 percent) (P less than 0.05). Consequently, there was no circadian variation in vascular resistance or blood flow after the infusion of this drug. In contrast, the vasodilation in response to sodium nitroprusside was similar at all three times of day. CONCLUSIONS. There is a circadian rhythm in basal vascular tone, due either partly or entirely to increased alpha-sympathetic vasoconstrictor activity during the morning. This variation may contribute to higher blood pressure and the increased incidence of cardiovascular events at this time of day.     

Increased Light Exposure Consolidates Sleep and Strengthens Circadian Rhythms in Severe Alzheimer's Disease Patients

Sleep in the nursing home environment is extremely fragmented, possibly in part as a result of decreased light exposure. This study examined the effect of light on sleep and circadian activity rhythms in patients with probable or possible Alzheimer's disease. Results showed that both morning and evening bright light resulted in more consolidated sleep at night, as measured with wrist actigraphy. Evening light also increased the quality of the circadian activity rhythm, as measured by a 5-parameter extended cosine model (amplitude, acrophase, nadir, slope of the curve, and relative width of the peak and trough). Increasing light exposure throughout the day and evening is likely to have the most beneficial effect on sleep and on circadian rhythms in patients with dementia. It would behoove nursing homes to consider increasing ambient light in multipurpose rooms where patients often spend much of their days.     

生物钟基因与心血管疾病

几乎各种生物的生理、生化和行为过程中都表现出一定的昼夜节律变化。昼夜节律生物钟(circa dianclock)就是设定并调控机体出现这种昼夜周期的系统,是一种以近似24h为周期的振荡器(oscilla tor);是机体为了更好地适应环境,在进化过程中自然选择作用下获得的[1]。该生物钟与昼-夜变换同步,使得机体不仅能适应由于地球自转带来的昼夜中的明暗变化,也能够适应地轴相对于太阳倾斜角度发生变化引起的昼夜长短变化。很早就已发现动物植物的生理行为呈现昼夜节律,但直到上世纪中期才发现该节律由内在的昼夜节律生物钟所控制[2]。1生物钟基因对果蝇…     

Postoperative circadian disturbances

An increasing number of studies have shown that circadian variation in the excretion of hormones, the sleep wake circle, the core body temperature rhythm, the tone of the autonomic nervous system and the activity rhythm are important both in health and in disease processes. An increasing attention has also been directed towards the circadian variation in endogenous rhythms in relation to surgery. The attention has been directed to the question whether the circadian variation in endogenous rhythms can affect postoperative recovery, morbidity and mortality. Based on the lack of studies where these endogenous rhythms have been investigated in relation to surgery we performed a series of studies exploring different endogenous rhythms and factors affecting these rhythms. We also wanted to examine whether the disturbances in the postoperative circadian rhythms could be correlated to postoperative recovery parameters, and if pharmacological administration of chronobiotics could improve postoperative recovery. Circadian rhythm disturbances were found in all the examined endogenous rhythms. A delay was found in the endogenous rhythm of plasma melatonin and excretion of the metabolite of melatonin (AMT6s) in urine the first night after both minor and major surgery. This delay after major surgery was correlated to the duration of surgery. The amplitude in the melatonin rhythm was unchanged the first night but increased in the second night after major surgery. The amplitude in AMT6s was reduced the first night after minimally invasive surgery. The core body temperature rhythm was disturbed after both major and minor surgery. There was a change in the sleep wake cycle with a significantly increased duration of REM-sleep in the day and evening time after major surgery compared with preoperatively. There was also a shift in the autonomic nervous balance after major surgery with a significantly increased number of myocardial ischaemic episodes during the nighttime period. The circadian activity rhythm was also disturbed after both minor and major surgery. The daytime AMT6s excretion in urine after major surgery was increased on the fourth day after surgery and the total excretion of AMT6s in urine was correlated to sleep efficiency and wake time after sleep onset, but was not correlated to the occurrence of postoperative cognitive dysfunction. We could only prove an effect of melatonin substitution in patients with lower than median pain levels for a three days period after laparoscopic cholecystectomy. In the series of studies included in this thesis we have systematically shown that circadian disturbances are found in the secretion of hormones, the sleep-wake cycle, core body temperature rhythm, autonomic nervous system tone, myocardial ischaemia and activity rhythm after surgery. Correlation exists between circadian rhythm parameters and measures of postoperative sleep quality and recovery. However, oral melatonin treatment in the first three nights after surgery, cannot yet be generally recommended for improvement of sleep quality or other recovery parameters based on the available results. It may be indicated in subgroups or if other perioperative treatment algorithms were used, but this has to be investigated in future trials.     

Biological rhythm and thromboembolic disease. Physiological, epidemiological and pharmacological aspects

Arterial and venous thromboembolic disorders are the leading cause of death in most of the advanced nations. The study of physiologic, epidemiologic and pharmacologic relationships of these disorders to biological rhythms, may lead to a better understanding and perhaps a better treatment. Chronophysiologic studies have shown that hemostatic variables follow circadian rhythms. The level of platelets aggregation and of blood coagulation has been found to be increased in the morning and decreased at night, whereas fibrinolytic activity is lower in the morning than in the evening. Chronoepidemiologic studies demonstrated a morning peak for arterial thromboembolic disorders and an evening peak for cerebral bleedings. These facts might partially be explained by circadian variations in hemostasis and suggest a chronotherapeutic approach in thromboembolic disorders. Unfractionated heparin, because of its antithrombotic effect, is one of the major drugs used to treat this disease. However, with such a treatment venous thrombosis recurs or bleeding complications occur yet in about 30% of patients. Chronopharmacologic studies indicate that anticoagulant effect of heparin is minimum in the morning and maximum at night, following the physiologic circadian variation of blood coagulation. Such results suggest that the heparin doses should be modulated as a function of administration times in order to increase its effectiveness and to minimize both bleeding risk and thrombosis. Further studies are needed to evaluate such a proposal.     

Altered circadian rhythms in rheumatoid arthritis patients play a role in the disease's symptoms

The circadian changes in the metabolism or nocturnal secretion of endogenous corticosteroids (reduction) observed in rheumatoid arthritis (RA) patients are responsible, in part, for the time-dependent changes that are observed in the inflammatory response and related early morning clinical symptoms of the disease. Melatonin (MLT), another circadian nocturnal hormone that is the secretory product of the pineal gland, has been implicated in the time-dependent RA inflammatory reaction with effects that are opposite to those of corticosteroids. As a consequence, altered functioning of the HPA axis (early morning reduced corticosteroid production) and of the pineal gland (night increased MLT production) found in RA patients, seem to be important factors in the appearance and perpetuation of the clinical circadian symptoms of the disease. Consistently, human proinflammatory Th1-type cytokine production (related to MLT stimulation) exhibits a diurnal rhythmicity with peak levels during the night and early morning, at a time when plasma cortisol (inducing the Th2-type cytokine production) is lowest and MLT is highest. Reduced daily light exposure as observed in northern Europe (Estonia), at least during the winter, might explain the higher and more prolonged serum MLT concentrations that were observed in northern RA patients, as well as some epidemiological features versus southern Europe patients.     

Severe mood dysregulation: in the "light" of circadian functioning

Severe affective and behavioral dysregulation, labeled as severe mood dysregulation (SMD), is a widely spread phenomenon among adolescent psychiatric patients. This phenotype constitutes severe impairment across multiple settings, including various symptoms, such as non-episodic anger, mood instability, and hyperarousal. Moreover, SMD patients often show depression and reduced need for sleep. Despite a lifetime prevalence of 3.3%, systematic research is still scarce, and treatments that have been established do not account for the range of symptoms present in SMD. Considering the circadian dysfunctions, two hormones, melatonin and cortisol, are essential. When these hormones are dysregulated, the circadian rhythm gets out of synchrony. Since evidence is emerging showing that the worse the sleep-wake cycle is entrained, the worse the psychiatric symptoms are depicted, the importance of proper circadian functioning becomes clear.Chronotherapy as the controlled exposure to environmental stimuli (e.g. light) acting on biological rhythms has shown therapeutic effects. In both seasonal and major depression chronotherapy has been implemented, decreasing depressive symptoms and stabilizing circadian rhythms. Preliminary evidence from SMD related disorders, namely attention-deficit/hyperactivity disorder and pediatric bipolar depression, indicates that morning light therapy elicits positive influences on other symptoms as well. Hence, light therapy might not only be effective for depressive symptoms and circadian rhythms, but might also be beneficial for symptoms including inattention and irritability.We hypothesize that light therapy might be a helpful adjunctive treatment enhancing affective and circadian functioning, and eliciting positive influences on behavior. Physiologically, changes of both cortisol levels and melatonin production are expected.     

Asymmetric dimethylarginine (ADMA) levels display a morning peak in patients with acute myocardial infarction

High Asymmetric Dimethylarginine (ADMA) levels are associated with increased platelet activity, elevated blood pressure, vasoconstriction and impaired vascular relaxation. We hypothesized that the myocardial infarction morning peak of occurrence is closely related to a morning peak of ADMA levels. We performed a cross-sectional study among patients with documented myocardial infarction who had been enrolled in the prospective MISSION! Intervention Study. In total, serum ADMA levels were measured in their acute setting of myocardial infarction in 120 patients. The frequency of myocardial infarction onset of symptoms and emergency coronary catheterization and the ADMA levels displayed a similar daily pattern with a morning peak between 06:00-11:59 h. The absolute ADMA levels peak was between 06:00-07:59 h with a median (interquartile range) peak value of 1.01 (0.84-1.21) μmol/L for the n=9 patients vs. 0.75 (0.61-0.89) μmol/L for the remaining 111 patients admitted throughout the rest of the 24-hour interval (p=0.003 for between groups comparison). The amplitude (95% 0.08 μmol/L (0.004-0.16) with p=0.042 for statistic model significance. In conclusion, ADMA levels display a 24-hour variation with a significant morning peak in patients with acute myocardial infarction. These findings may relate ADMA levels to the acute onset of thrombotic cardiovascular events.     

Blunted cortisol rhythm is associated with learning impairment in aged hamsters

In mammals, the cognitive decline that accompanies unsuccessful aging is associated with circadian rhythm dysfunction and increased levels of circulating glucocorticoids. The possible causal relations among these factors are not known. To test for primary effects of circadian clock dysfunction versus increased glucocorticoid levels as contributors to age-related learning impairment, we measured cortisol and wheel-running rhythms along with context learning in aged hamsters (15-18 months). At this age, locomotor rhythms of learners and nonlearners were found to be indistinguishable. However, plasma cortisol levels were lower, and the amplitude of the cortisol rhythm was reduced in the impaired animals. These data suggest that age-related cognitive decline may be related more to a loss of hormone rhythmicity than to a loss of behavioral rhythmicity or an increase in hormone level.     

Circadian rhythms of activity in healthy young and elderly humans

Patterns of activity of healthy adult humans were monitored in a controlled environment for several days using a wrist-mounted ambulatory activity meter. Subjects were 15 young males, 14 young females, 17 elderly males and 23 elderly females. Substantial differences in the absolute levels and patterns of daily rest and activity across age groups were observed. The elderly subjects were somewhat more active than the young subjects overall, especially in the early morning. Consistent with their increased levels of daytime activity the elderly subjects reported less sleepiness, especially in the morning, than the young volunteers. The age groups also differed significantly on all circadian parameters. The mean acrophase (peak of a sinusoid fitted to the activity rhythms) of the elderly group occurred at 1326 hr, significantly earlier than in the young group (1513 hr). The amplitude and the mesor (mean level) of the rhythms were both greater in the elderly group. It is uncertain whether these differences reflect changes in behavior that occur as a consequence of the aging process, previously-established differences in the life styles of the different populations studied, or some other factor. These findings suggest that levels and rhythms of daily activity in healthy elderly people are often well preserved and may not deteriorate as readily as had been assumed.     

Locomotor, feeding and melatonin daily rhythms in sharpsnout seabream (Diplodus puntazzo)

Sharpsnout seabream is a marine teleost of increasing interest for Mediterranean aquaculture, but there is still a lack of information regarding its circadian organization. In this study, we have investigated sharpsnout seabream locomotor activity, feeding and plasma melatonin daily rhythms under a 12:12-h LD cycle, as well as the persistence of locomotor activity circadian rhythmicity under constant light (LL) conditions. When submitted to an LD cycle, most sharpsnout seabream displayed a diurnal locomotor pattern, with an average 74% of activity recorded during daytime. However, along the experiment 40% of fish spontaneously changed their locomotor rhythm phasing and became nocturnal. Feeding behaviour, nevertheless, remained strictly diurnal in all cases, with 97% of food demands being made during the light period. Free-running locomotor rhythms were recorded in one third of the fish kept under LL. Daily plasma melatonin levels displayed a rhythmic profile, with low daytime values (111 pg/ml) and high nighttime concentrations (791 pg/ml). Taken together, these results evidence a high degree of plasticity for sharpsnout seabream activity patterns, as well as phasing independence of locomotor and feeding rhythms. Finally, the existence of a well-defined daily rhythm of plasma melatonin was found.     

The relation between hepatitis C virus and coronary heart disease

It is well known that chronic hepatitis C is associated with insulin resistance and metabolic syndrome which are risk factors for atherosclerosis and coronary heart disease. As a result, chronic hepatitis C might be thought, through its association with metabolic syndrome, to increase the risk of myocardial infarction. However, unexpectedly it was found that HCV infection is not associated with an increased risk of myocardial infarction. We are providing here an hypothesis of the mechanism through which HCV infection does not increase the risk for myocardial infarction and also may be protecting against some cardiovascular risks that typically develop in many patients with metabolic syndrome who do not have chronic hepatitis C. The suggested mechanism includes factors that are normal consequences of chronic hepatitis, such as: significant decrease in cholesterol and LDL levels; defected blood clotting system; impaired myocardial function; decreased venous return and central venous pressure; increased nitric oxide and TNF alpha levels; and diminished cardiac beta receptors signal transduction. All these factors contribute to a protective effect against cardiac ischemia and coronary heart disease. We suggest further studies to investigate this hypothesis.     

Rhythms in behaviors, body temperature and plasma corticosterone in SCN lesioned rats given methamphetamine

In aperiodic rats with lesions in the suprachiasmatic nuclei (SCN), rhythms with a circadian period in spontaneous locomotion, wheel-running, feeding, drinking, body temperature and plasma corticosterone were restored by chronic administration of methamphetamine. These rhythms were not entrained by a light-dark cycle. Wheel-running, feeding and drinking rhythms in individual rats were in phase in terms of ultradian bout as well as circadian fluctuation. Rhythms of the intraperitoneal temperature appeared accompanying the spontaneous locomotor rhythm. The phase relation between the two rhythms was similar to that of SCN dependent rhythms. Plasma corticosterone also fluctuated in a circadian fashion. The corticosterone peak preceded the activity onset of locomotor rhythm by a few hours, which was similar to the phase relation observed in the SCN intact animals. It is concluded that the oscillatory mechanism underlying the spontaneous locomotor rhythm in SCN lesioned and methamphetamine treated rats drives also other physiological rhythms. The phase-relations among them were similar to those of rhythms driven by the circadian pacemaker in the SCN.