Circadian Variations of Heart Rate and Premature Beats in Healthy Subjects and in Patients with Previous Myocardial Infarction

Chronobiological analysis of the circadian variations of heart rate, ventricular and atrial ectopies, was carried out on 11 patients with previous myocardial infarction matched with 11 controls. Individual circadian rhythms in heart rate were seen in all the control subjects but only in 6 patients with previous myocardial infarction. The behaviour of the individual circadian rhythms of premature beats was not significantly different between the two groups. A significant group rhythm in ectopies was not demonstrated, nevertheless a trend to higher frequency of arrhythmias during the activity span was detected. These results do not allow to postulate a circadian pattern of arrhythmias common to all the subjects examined. Therefore, the individual circadian behaviour of premature atrial and ventricular beats should be recognized for monitoring antiarrhythmic therapy. A significant group rhythm in heart rate was demonstrated for the two populations studied and linear discriminant analysis showed that the amplitude of this rhythm was significantly lower in patients than in controls. Possibly, myocardial infarction may affect the sinus node function producing a “flattened” range of heart rates during the 24 hours.     

Ten-Year-Replicated Circadian Profiles for 36 Physiological,Serological and Urinary Variables in Healthy Men

At 3-hr intervals over a 24-hr span, 36 systemic, serologic and urinary variables were examined in 7 men in their mid 20's in the Spring of 1969, and again in the same 7 men in the Spring of 1979 under a similar chronobiologic protocol, using the same chemical and numerical analytical procedures. The variables examined for rhythms by cosinor were: vital signs—blood pressure (systoliC., diastoliC., pulse pressure and mean arterial pressure), heart rate, intraocular pressure (left and right), oral temperature; serum components—albumin, albumin/globulin ratio, total bilirubin, calcium, carbon dioxide, chlorides, bilirubin, cholesterol, globulin, glucose, potassium, sodium, sodium/potassium ratio, transaminase, triglycerides, total protein, urea nitrogen; and urine components—calcium, calcium/magnesium ratio, creatinine, magnesium, pH, potassium, sodium, sodium/potassium ratio, urea clearance, urea nitrogen, volume and zinc. Although all subjects appeared clinically healthy in 1969 and in 1979, certain inter-study differences were observed in a number of rhythm parameters of different variables. Statistically significant increases in mesor for the group as a whole were observed forserum Ca, cholesterol, Cl, CO₂, K, Na, and while statistically significant mesor decreases for a group as a whole were noted in serum glucose and transaminase. Statistically significant increases in amplitude for the group as a whole were observed in serum chloride and urinary Na/K ratio, while statistically signficiant decreases were observed in amplitude for blood pressure, heart rate, serum albumin, A/G ratio, globulin, glucose, protein, sodium and transaminase. For the group as a whole, a statistically significant advance in acrophase was observed in serum transaminase, while a statistically significant delay in acrophase was observed for serum A/G ratio, globulin, glucose, potassium, protein, sodium and for urinary magnesium. Statistically significant by sign test, but not by cosinor, was a numerical mesor increase for urinary urea clearance, a numerical decrease in mesor for urinary zinc; a numerical amplitude decrease for serum cholesterol; and a numerical delay in acrophase for oral temperature and serum cholesterol, CO², and globulin in all men examined. Only mesor changes in serum cholesterol and urinary Ca/Mg were positively correlated with the change in body size over the 10-year span between studies.

From a circadian chronobiologic perspective, the immense amount of data uniquely reviewed in this report across a 10-year span in seven healthy individuals serves a useful beginning to the study of the effects of normal aging upon commonly measured physiologic and biochemical variables and, more importantly, upon the circadian rhythm characteristics of these variables. A great deal of supposition about what happens to the mesor, amplitude and acrophase of an individual's circadian rhythms in a variety of endpoints has been based upon transverse studies of short duration and relatively few longterm studies. The further accumulation of data such as presented here and similar long-term longitudinal time series can have no adequate substitute for truly understanding whether reproducible age-related changes in circadian rhythms occur as individuals age.

With these qualifications and with the further qualification that the timing of our observations within the aging process (mid-20's and mid-30's) may be suboptimal for conclusions about aging, very interesting trends definitely appear worth comment. There is some evidence in these data that the flattening of circadian rhythms may really accompany advancing age. In grouped data, this fall in amplitude may be secondary to an isolated fall in predictable swing around the mesor or a combination of this and increased variability of the acrophase with or without amplitude changes. The data are not robust enough to be sure of the relative contribution of these two components. In any event, the circadian amplitude of each and every physiologic variable studied demonstrated a tendency to fall between the mid-20's and mid- 30's. This tendency toward a flattening of circadian variability is also a very prominent property of many of the serum chemistries which were measured. The circadian patterns of excretion of substances in the urine change much less between the mid-20's and mid-30's in our subjects. These findings may indicate a separate effect of aging especially upon metabolic hepatic variables and upon nephrologic circadian rhythms. Cardiovascular rhythms seem to change more in parallel with hepatic metabolic rhythms in contradistinction to the kidney-related serum and urinary rhythms.

Further, ongoing statistical analyses may hopefully turn up interesting and relevant cross-correlations among the individual data themselves in each study year and between the 10-year span, as well as with rhythm (mesor, amplitude and acrophase) and other physiologic characteristics of each subject. Planned re-observation of what happens to the circadian time structure of these seven individuals in their mid-40's will prove invaluable to further sorting out of the effects of aging upon circadian time structure.     

Metabolic cycles are linked to the cardiovascular diurnal rhythm in rats with essential hypertension

Background

The loss of diurnal rhythm in blood pressure (BP) is an important predictor of end-organ damage in hypertensive and diabetic patients. Recent evidence has suggested that two major physiological circadian rhythms, the metabolic and cardiovascular rhythms, are subject to regulation by overlapping molecular pathways, indicating that dysregulation of metabolic cycles could desynchronize the normal diurnal rhythm of BP with the daily light/dark cycle. However, little is known about the impact of changes in metabolic cycles on BP diurnal rhythm.

Methodology/Principal Findings

To test the hypothesis that feeding-fasting cycles could affect the diurnal pattern of BP, we used spontaneously hypertensive rats (SHR) which develop essential hypertension with disrupted diurnal BP rhythms and examined whether abnormal BP rhythms in SHR were caused by alteration in the daily feeding rhythm. We found that SHR exhibit attenuated feeding rhythm which accompanies disrupted rhythms in metabolic gene expression not only in metabolic tissues but also in cardiovascular tissues. More importantly, the correction of abnormal feeding rhythms in SHR restored the daily BP rhythm and was accompanied by changes in the timing of expression of key circadian and metabolic genes in cardiovascular tissues.

Conclusions/Significance

These results indicate that the metabolic cycle is an important determinant of the cardiovascular diurnal rhythm and that disrupted BP rhythms in hypertensive patients can be normalized by manipulating feeding cycles.     

Circadian variations in rat serum and urinary calcium and phosphorus. Reflections on the Ca/PO4 ratio

Daily variations of serum and urine calcium and phosphate were determined in young and adult rats of both sexes. The animals were maintained in natural conditions of illumination and feeding ad libitum. The twenty-four hour rhythm of the serum levels and urinary excretion of these electrolytes in male rats is confirmed. This rhythm is markedly modified in young females and less in adult females. Evidence for a circadian rhythm of the Ca/PO4 ratio appears in all groups of rats. The rhythms of serum and urine Ca/PO4 rations are similar in all experimental groups.     

Circadian rhythms of electrolyte and 17-hydroxycorticosteroid excretion in hyperthyroidism and hypothyroidism.

The circadian rhythms of excretion of sodium, potassium, calcium, magnesium, phosphorus and 17-hydroxycorticosteroid (17-ohcs) were determined in five normal subjects, in six patients with hyperthyroidism and five with hypothyroidism. Constant diets with identical 3-hourly feedings were employed, and urine collections were made every 3 hrs during a 3-day study period. The circadian patterns of urinary excretion of sodium, potassium and 17-OHCS were similar in all three groups with distinct daytime peaks and nighttime nadirs. The total quantities of the ions and 17-OHCS excreted were greater in hyperthyroid than in hypothyroid patients with the greatest difference noted with the 17-OHCS. The rhythms for calcium, magnesium and phosphorus excretion were accentuated in hyperthyroid patients but similar to those in normal subjects with early morning calcium and magnesium peaks and a phosphorus peak approximately 12 hrs later. While a similar although blunted circadian pattern for calcium and perhaps magnesium excretion was noted in hypothyroid patients, their phosphorus rhythms were distorted and rather flat. These latter results confirm the observation of MINTZ et al. and are compatible with their interpretation that thyroid hormone is permissibly necessary for the expression of a normal phosphaturic rhythm and that the circulating level of thyroid hormone influences the amplitude of the phosphaturic rhythm.     

Circadian placebo and ACTH effects on urinary cortisol in arthritics

The effect of placebo and ACTH-1-17 (Synchrodyn®, Hoechst) upon urinary free cortisol was examined at 5 different circadian stages on 10 men with Steinbrocker Stage II–III rheumatoid arthritis. A mean cosinor analysis of urinary cortisol data from the subjects prior to treatment with either ACTH or placebo revealed a statistically highly-significant rhythm. A circadian variation in a response of urinary free cortisol to a placebo was also seen. Moreover, the response of the midline-estimating statistic of rhythm (rhythm-adjusted circadian average) of urinary free cortisol to ACTH-1-17 by patients with rheumatoid arthritis is circadian rhythmic. This reactivity rhythm is out of phase with the spontaneous rhythm in urinary cortisol acrophases—in the tests limited thus far to midsummer. The further assessment of the circadian component in the context of broader interactions by rhythms with other frequencies in various conditions in health and disease is warranted by the demonstration of rhythms here presented for men with rheumatoid arthritis.     

Different circadian pacemakers control feeding and locomotor activity rhythms in European starlings

Summary In higher organisms, many physiological and behavioral functions exhibit daily variations, generated by endogenous circadian oscillators. It is not yet clear whether all the various rhythms that occur within an individual depend on one and the same pacemaker or whether different pacemakers are involved. To examine this question, the feeding and perch-hopping rhythms were measured in European starlings (Sturnus vulgaris) under light-dark cycles and continuous dim light. In dim light, the internal phase relationship between the feeding and perch-hopping rhythms changed systematically as a function of the circadian period, and the two rhythms could even dissociate and show different circadian periods in individuals with extremely long or extremely short circadian periods. Moreover, in some birds kept on lowamplitude light-dark cycles, the rhythm of feeding was synchronized 180° out of phase with the rhythm of locomotor activity. These results strongly suggest that in the European starling the feeding and locomotor activity rhythms are controlled by separate circadian pacemakers.     

Disruption of Daily Rhythms by High-Fat Diet Is Reversible

In mammals a network of circadian clocks coordinates behavior and physiology with 24-h environmental cycles. Consumption of high-fat diet disrupts this temporal coordination by advancing the phase of the liver molecular clock and altering daily rhythms of eating behavior and locomotor activity. In this study we sought to determine whether these effects of high-fat diet on circadian rhythms were reversible. We chronically fed mice high-fat diet and then returned them to low-fat chow diet. We found that the phase of the liver PERIOD2::LUCIFERASE rhythm was advanced (by 4h) and the daily rhythms of eating behavior and locomotor activity were altered for the duration of chronic high-fat diet feeding. Upon diet reversal, the eating behavior rhythm was rapidly reversed (within 2 days) and the phase of the liver clock was restored by 7 days of diet reversal. In contrast, the daily pattern of locomotor activity was not restored even after 2 weeks of diet reversal. Thus, while the circadian system is sensitive to changes in the macronutrient composition of food, the eating behavior rhythm and liver circadian clock are specifically tuned to respond to changes in diet.     

The Utility of the Swine Model to Assess Biological Rhythms and Their Characteristics during Different Stages of Residence in a Simulated Intensive Care Unit: A Pilot Study

The purpose of this pilot study was to explore the utility of the mammalian swine model under simulated intensive care unit (sICU) conditions and mechanical ventilation (MV) for assessment of the trajectory of circadian rhythms of sedation requirement, core body temperature (CBT), pulmonary mechanics (PM) and gas exchange (GE). Data were collected prospectively with an observational time-series design to describe and compare circadian rhythms of selected study variables in four swine mechanically ventilated for up to seven consecutive days. We derived the circadian (total variance explained by rhythms of τ between 20 and 28?h)/ultradian (total variance explained by rhythms of τ between 1 and <20?h) bandpower ratio to assess the robustness of circadian rhythms, and compare findings between the early (first 3 days) and late (subsequent days) sICU stay. All pigs exhibited statistically significant circadian rhythms (τ between 20 and 28?h) in CBT, respiratory rate and peripheral oxygen saturation, but circadian rhythms were detected less frequently for sedation requirement, spontaneous minute volume, arterial oxygen tension, arterial carbon dioxide tension and arterial pH. Sedation did not appear to mask the circadian rhythms of CBT, PM and GE. Individual subject observations were more informative than group data, and provided preliminary evidence that (a) circadian rhythms of multiple variables are lost or desynchronized in mechanically ventilated subjects, (b) robustness of circadian rhythm varies with subject morbidity and (c) healthier pigs develop more robust circadian rhythm profiles over time in the sICU. Comparison of biological rhythm profiles among sICU subjects with similar severity of illness is needed to determine if the results of this pilot study are reproducible. Identification of consistent patterns may provide insight into subject morbidity and timing of such therapeutic interventions as weaning from MV.     

Urinary excretion of immunoreactive prostaglandin E: A circadian rhythm and the effect of posture

The excretion of urinary immunoreactive prostaglandin E (iPGE), sodium, potassium, creatinine and volume was studied in 4 hr collections in normal women at normal activity. iPGE exhibited a circadian rhythm with an amplitude of 29% and peak excretion at 4:55 P.M. There were also significant circadian rhythms for sodium, potassium, creatinine, and volume, all peaking in late afternoon. There were no significant changes either in the total excretion or in the circadian rhythms of iPGE, potassium, or creatinine excretion when the subjects remained in bed for an entire day while the circadian rhythms of sodium and volume were significantly modified in amplitude and phase, respectively. Urinary aldosterone excretion decreased significantly when the subjects were at bed rest. iPGE excretion increased 33% when subjects were first recumbent and then erect for consecutive 4 hr periods on the same day (but when subjects were erect 1 day for a 4 hr period, iPGE excretion was lower by 32% than for the same 4 hr period the preceding day when they were recumbent). These data indicate that: 1) the sympathetic nervous system and renin-angiotensin-aldosterone system do not affect the circadian rhythm of urinary iPGE, and 2) short-term experiments of prostaglandin E excretion must be designed to avoid misleading results due to the circadian rhythm.     

Ultradian Rhythm of Activity in Japanese Quail Groups under Semi-Natural Conditions during Ontogeny: Functional Aspects and Relation to Circadian Rhythm

The function of ultradian rhythms is not yet clearly elucidated. In particular, short-term rhythms are expressed during early ontogeny, especially in broods of precocial birds. We investigated the relationship between the clarity of the ultradian rhythm of the activity/rest cycle of a group of young Japanese quail (Coturnix japonica) and the level of social synchronisation and spatial cohesion between the birds within that group. The subjects were descended from two lines selected for either very pronounced rhythmic or arrhythmic circadian activity. We found a positive relationship between the clarity of the ultradian rhythm of the activity/rest cycle when birds were young and the clarity of the circadian rhythm of feeding activity when birds were older, but still immature. The temporal organisation of the behaviour of the chicks from these two lines was observed in outdoor aviaries, when they were 4, 8, 12 and 15 days old. The mean ultradian period expressed by groups of 12 chicks was variable, with a minimum of 6 minutes. The ultradian period lengthened regularly as chicks grew older, and reached approximately 40 min on day 15. The clarity of the ultradian rhythmicity of group activity was linked to the level of inter-individual social synchronisation and of spatial cohesion; the more pronounced the ultradian rhythms of a group, the greater the temporal and spatial cohesion of the chicks within the group. Moreover, these characteristics varied with the age of the chicks. Finally, chicks in the less rhythmic groups weighed less. These results stress the adaptive value of this temporal organisation strategy under natural conditions.     

Circadian placebo and ACTH effects on urinary cortisol in arthritics

The effect of placebo and ACTH-1-17 (Synchrodyn®, Hoechst) upon urinary free cortisol was examined at 5 different circadian stages on 10 men with Steinbrocker Stage II–III rheumatoid arthritis. A mean cosinor analysis of urinary cortisol data from the subjects prior to treatment with either ACTH or placebo revealed a statistically highly-significant rhythm. A circadian variation in a response of urinary free cortisol to a placebo was also seen. Moreover, the response of the midline-estimating statistic of rhythm (rhythm-adjusted circadian average) of urinary free cortisol to ACTH-1-17 by patients with rheumatoid arthritis is circadian rhythmic. This reactivity rhythm is out of phase with the spontaneous rhythm in urinary cortisol acrophases—in the tests limited thus far to midsummer. The further assessment of the circadian component in the context of broader interactions by rhythms with other frequencies in various conditions in health and disease is warranted by the demonstration of rhythms here presented for men with rheumatoid arthritis.     

Marker rhythms of circadian system function: a study of patients with metastatic colorectal cancer and good performance status

Cancer patients may exhibit normal or altered circadian rhythms in tumor and healthy tissues. Four rhythms known to reflect circadian clock function were studied in 18 patients with metastatic colorectal cancer and good performance status. Rest-activity was monitored by wrist actigraphy for 72 h before treatment, and its circadian rhythm was estimated by an autocorrelation coefficient at 24h and a dichotomy index that compared the activity level when in and out of bed. Blood samples (9-11 time points, 3-6 h apart) were drawn on day 1 and day 4 of the first course of chronochemotherapy (5-fluorouracil: 800 mg/m2/day; folinic acid: 300 mg/m2/day; oxaliplatin: 25 mg/m2/day). Group 24h rhythms were validated statistically for plasma concentrations of melatonin, 6-alpha-sulfatoxymelatonin, and cortisol and for lymphocyte counts. Significant individual 24h rhythms were displayed in melatonin by 15 patients, cortisol by seven patients, lymphocytes by five patients, and prominent circadian rhythms in activity were displayed by 10 patients; only one patient exhibited significant rhythms in all the variables. The results suggest the rhythms of melatonin, cortisol, lymphocytes, and rest/activity reflect different components of the circadian system, which may be altered differently during cancer processes. Such 24h rhythm alterations appeared to be independent of conventional clinical factors.     

Small bowel and plasma gastrin rhythms in cats

The purpose of this experiment was to study the possible role of the gastric antrum and small bowel in the rhythm(s) of plasma gastrin. The cat was used as the laboratory animal. Three groups of cats were provided with a gastric fistula for the study of gastric acid and plasma gastrin rhythms. The first group (N = 7) served as controls. A second group (N = 3) was antrectomized and later subjected to a 80% small bowel resection. Gastric acid secretions were collected every 30 min from 0800 to 2400. Blood samples for determination of gastrin were drawn every 2 hr from 0800 to 2400. In control animals a circadian (i.e. approximately 24 hr) and 3 ultradian (i.e. less than 24 hr) rhythms were detected for acid output. In the antrectomized cats, circadian and ultradian rhythms were documented. After small bowel resection circadian and ultradian rhythms in gastric acid secretion were observed. For plasma gastrin, circadian and ultradian rhythms were found in the control cats. In the antrectomized cats no rhythms were observed. After small bowel resection an ultradian rhythm reappeared in these antrectomized cats. Removal of the antrum in the cat induces disappearance of circadian and ultradian rhythms of plasma gastrin but fails to modify the acid rhythms. Small bowel resection results in the reappearance of an ultradian rhythm for plasma gastrin and a shift in acrophase for the circadian rhythm in acid secretion.     

Ultradian Rhythm of Activity in Japanese Quail Groups under Semi-Natural Conditions during Ontogeny: Functional Aspects and Relation to Circadian Rhythm

The function of ultradian rhythms is not yet clearly elucidated. In particular, short-term rhythms are expressed during early ontogeny, especially in broods of precocial birds. We investigated the relationship between the clarity of the ultradian rhythm of the activity/rest cycle of a group of young Japanese quail (Coturnix japonica) and the level of social synchronisation and spatial cohesion between the birds within that group. The subjects were descended from two lines selected for either very pronounced rhythmic or arrhythmic circadian activity. We found a positive relationship between the clarity of the ultradian rhythm of the activity/rest cycle when birds were young and the clarity of the circadian rhythm of feeding activity when birds were older, but still immature. The temporal organisation of the behaviour of the chicks from these two lines was observed in outdoor aviaries, when they were 4, 8, 12 and 15 days old. The mean ultradian period expressed by groups of 12 chicks was variable, with a minimum of 6 minutes. The ultradian period lengthened regularly as chicks grew older, and reached approximately 40 min on day 15. The clarity of the ultradian rhythmicity of group activity was linked to the level of inter-individual social synchronisation and of spatial cohesion; the more pronounced the ultradian rhythms of a group, the greater the temporal and spatial cohesion of the chicks within the group. Moreover, these characteristics varied with the age of the chicks. Finally, chicks in the less rhythmic groups weighed less. These results stress the adaptive value of this temporal organisation strategy under natural conditions.     

Consistent Changes in the Circadian Rhythms of Blood Pressure and Atrial Natriuretic Peptide in Congestive Heart Failure

We demonstrated in previous works that the circadian rhythms of blood pressure (BP) and atrial natriuretic peptide (ANP) are antiphasic in normal subjects and in essential hypertension. The aim of the present study was to assess the circadian rhythms of BP and ANP in 20 patients with stable congestive heart failure (CHF), divided into two groups of 10 according to their New York Heart Association functional class. A matched control group of 10 normal volunteers was also studied. Noninvasive BP monitoring at 15-min intervals was performed for 24 h. Peripheral blood samples were also obtained at 4-h intervals starting from 08:OO h. The mean (±SEM) circadian mesors of ANP plasma levels were 13.4 ± 1.7 pmol/L in the control group, 28.6 ± 2.4 pmol/L in the group of 10 patients in class 11, and 81.5 ± 12 pmol/L in the group of 10 patients in class 111-IV. In normal subjects, plasma ANP concentration was highest at 04:OO h (21.5 ± 2.7 pmol/L) and lowest at 16:OO h (8.8 ± 2.4 pmol/L; p < 0.01). Both groups of patients with CHF showed no significant circadian change in the plasma levels of ANP and also a significantly blunted circadian rhythm of BP. Cosinor analysis confirmed the loss of the circadian rhythms of ANP and BP in CHF patients. Our findings support the existence of a causal relationship between the circadian rhythms of ANP and BP.     

Consistent changes in the circadian rhythms of blood pressure and atrial natriuretic peptide in congestive heart failure.

We demonstrated in previous works that the circadian rhythms of blood pressure (BP) and atrial natriuretic peptide (ANP) are antiphasic in normal subjects and in essential hypertension. The aim of the present study was to assess the circadian rhythms of BP and ANP in 20 patients with stable congestive heart failure (CHF), divided into two groups of 10 according to their New York Heart Association functional class. A matched control group of 10 normal volunteers was also studied. Noninvasive BP monitoring at 15-min intervals was performed for 24 h. Peripheral blood samples were also obtained at 4-h intervals starting from 08:00 h. The mean (+/- SEM) circadian mesors of ANP plasma levels were 13.4 +/- 1.7 pmol/L in the control group, 28.6 +/- 2.4 pmol/L in the group of 10 patients in class II, and 81.5 +/- 12 pmol/L in the group of 10 patients in class III-IV. In normal subjects, plasma ANP concentration was highest at 04:00 h (21.5 +/- 2.7 pmol/L) and lowest at 16:00 h (8.8 +/- 2.4 pmol/L; p less than 0.01). Both groups of patients with CHF showed no significant circadian change in the plasma levels of ANP and also a significantly blunted circadian rhythm of BP. Cosinor analysis confirmed the loss of the circadian rhythms of ANP and BP in CHF patients. Our findings support the existence of a causal relationship between the circadian rhythms of ANP and BP.     

Circadian and circannual rhythms of hormonal variables in elderly men and women

A group of fourteen men (73 ± 5 yr of age), and eighteen women (77 ± 7 yr of age) institutionalized at the Berceni Clinical Hospital, Bucharest, Romania, were studied over a 24-hr span once during each season (winter, spring, summer and fall). All subjects followed a diurnal activity pattern with rest at night and ate three meals per day with breakfast at about 0830, lunch at about 1300 and dinner at about 1830. The meals were similar, although not identical for all subjects during all seasons. On each day of sampling blood was collected at 4-hr intervals over a 24-hr span. Seventeen hormonal variables were determined by radioimmunoassay. Statistically significant circadian rhythms were detected and quantitated by population mean cosinor analysis in pooled data from all four seasons in both sexes for ACTH, aldosterone, Cortisol, C-peptide, dehydroepiandrosterone-sulfate (DHEA-S), immunoreactive insulin, prolactin, 17-OH progesterone, testosterone, total T₄ and TSH. In women, estradiol and progesterone also were determined and showed a circadian rhythm during all seasons. Total T, and FSH showed circadian rhythm detection by cosinor analysis in the men only; LH showed no consistent circadian rhythm as group phenomenon in men or women.

A circannual rhythm was detected using the circadian means of each subject at each season as input for the population mean cosinor in the women for ACTH, C-peptide, DHEA-S, FSH, LH, progesterone, 17-OH progesterone and TSH. In the men, a circannual rhythm was detected for ACTH, FSH, insulin, LH, testosterone and T₃. There were phase differences between men and women in ACTH, FSH and LH. In those functions in which both the circadian and circannual rhythms were statistically significant, a comparison of the amplitudes showed in the women a higher circannual rather than circadian amplitude for DHEA-S. In 17-OH progesterone, TSH and C-peptide, the circadian amplitude in women was larger. In men, the circannual amplitude of T₃ was larger than the circadian amplitude and in insulin the circadian amplitude was larger than the circannual amplitude. There was no statistically significant difference between the circadian and circannual amplitudes in the women in ACTH and progesterone and in the men in ACTH and testosterone.     

Persistance of phase-coupling between the circadian rhythms of hypophyseal hormones in free-running rats

The circadian rhythms in plasma ACTH, TSH, LH and PRL were explored in sighted or blind, spayed and estrogen-implanted rats. A marked endogenous circadian rhythmicity was shown to persist in the blind animals for the 4 endocrine rhythms. The endogenous rhythms also kept very close reciprocal phase relationship as in the synchronized state, and they were peaking almost simultaneously, after 60 d. of free-running. Finally the endogenous hormonal rhythm maintained their usual phase relationships with the endogenous activity rhythm, so that the circadian phase of increased hormonal secretion coincided with the circadian resting phase of the sleep/wake rhythm. These results are discussed in the light of the alternate theory of one vs multiple but phase-locked circadian pacemakers driving endocrine and behavioral circadian rhythms.     

Small Bowel and Plasma Gastrin Rhythms in Cats

The purpose of this experiment was to study the possible role of the gastric antrum and small bowel in the rhythm(s) of plasma gastrin. The cat was used as the laboratory animal. Three groups of cats were provided with a gastric fistula for the study of gastric acid and plasma gastrin rhythms. The first group (N = 7) served as controls. A second group (N = 3) was antrectomized and later subjected to a 80% small bowel resection. Gastric acid secretions were collected every 30 min from 0800 to 2400. Blood samples for determination of gastrin were drawn every 2hr from 0800 to 2400. In control animals a circadian (i.e.<24hr) and 3 ultradian (i.e.<24 hr) rhythms were detected for acid output. In the antrectomized cats, circadian and ultradian rhythms were documented. After small bowel resection circadian and ultradian rhythms in gastric acid secretion were observed. For plasma gastrin, circadian and ultradian rhythms were found in the control cats. In the antrectomized cats no rhythms were observed. After small bowel resection an ultradian rhythm reappeared in these antrectomized cats. Removal of the antrum in the cat induces disappearance of circadian and ultradian rhythms of plasma gastrin but fails to modify the acid rhythms. Small bowel resection results in the reappearance of an ultradian rhythm for plasma gastrin and a shift in acrophase for the circadian rhythm in acid secretion.