Loss Of Circadian Variation Research Articles

High-Fat Diet-Induced Obesity Ablates Gastric Vagal Afferent Circadian Rhythms.

Appropriate circadian control of food intake is vital for maintaining metabolic health. Diet-induced obesity is associated with strong circadian changes in food intake, but the contributing mechanisms have yet to be determined. Vagal afferents are involved in regulation of feeding behavior, particularly meal size, and have been shown to exhibit circadian fluctuation in mechanosensitivity, potentially allowing for time of day-specific levels of satiety signaling. Our study indicates that, in diet-induced obesity, these circadian fluctuations in gastric vagal afferent mechanosensitivity are lost. This was accompanied by increased light phase eating, particularly increased meal size. This is the first evidence that diet-induced disruption to vagal afferent signaling may cause a perturbation in circadian eating patterns.

Abstract 302: Sex Differences In Nonlinear Dynamics And Their Circadian Variation In Control Dogs And In A New Arrhythmogenic Canine Model Of Heart Failure

Introduction: Females can be more arrhythmogenic than males, and this sex difference can persist with development of chronic heart failure (CHF). The aim of this study was to investigate sex differences in the arrhythmogenic substrate in control dogs and in a new arrhythmogenic canine model of CHF. Methods: CHF was induced in 30 dogs by aortic insufficiency and aortic constriction. Holter monitoring assessed VT and PVCs from 30 dogs, as well as traditional HRV measures and nonlinear dynamics (including correlation dimension (CD), detrended fluctuations analysis α1 (DFAα1), and Shannon entropy (SE)) at baseline, 240 days (240d) and 720 days (720d) after CHF induction. Results: At baseline, females had lower LF/HF (0.27±0.03 vs 0.33±0.02, p=0.04), CD (1.60±0.17 vs 2.21±0.15, p=0.01), DFAα1 (0.62±0.03 vs 0.72±0.03, p=0.03), and SE (2.99±0.02 vs 3.10±0.03, p=0.03 vs males). Females lacked circadian variation in LF/HF, DFAα1, and SE while males had circadian variation in all of these. Of 11 dogs with frequent runs of VT and PVCs, 95% and 91% of total VT runs and total PVCs, respectively, were in females. With CHF, all these linear and nonlinear parameters progressively declined in males and females. CHF females had less decline in LF/HF than males so that by 720 days there was no more sex difference (0.24±0.06, 0.17±0.03 in females vs 0.22±0.05, 0.18±0.01 in males at 240d, 720d). However, for nonlinear parameters of CD, DFAα1, and SE, CHF females had lower values than males (CD: 1.56±0.21, 0.99±0.32 vs 1.87±0.24, 1.50±0.34; DFAα1: 0.51±0.05, 0.43±0.04 vs 0.54±0.07, 0.48±0.04; and SE 2.93±0.08, 2.76±0.08 vs 3.01±0.11, 2.91±0.04 in females vs males at 240d, 720d). With CHF, circadian variation in CD, DFAα1, and SE were lost in both males and females. Conclusions: There are sex differences in the arrhythmogenic substrate in control dogs and in this new arrhythmogenic canine model of moderate CHF. At baseline, females have lower sympathetic stimulation, reduced cardiac chaos, and loss of circadian variation in nonlinear dynamics. With CHF, sex differences in nonlinear dynamics persist; this reflects a loss of complexity and fractal properties that could contribute to increased arrhythmias in female CHF dogs.

Ambulatory blood pressure measurement in the renal patient.

Ambulatory blood pressure monitoring has been steadily growing in popularity as equipment becomes more accurate, affordable, and patient-friendly. In addition, software packages are more powerful and physician-customizable, and more physicians are accepting of ambulatory blood pressure monitoring's advantages. Summarizing the studies that deal mainly with hemodialysis patients, there are clear advantages to using more than isolated pre- and posthemodialysis blood pressure readings. If enough predialysis blood pressure readings are taken and averaged, this is a reasonable guide to end-organ damage (ie, left ventricular hypertrophy). Home and ambulatory blood pressure-derived values are complementary, and only this approach can discern any further contribution from diurnal blood pressure elevation. The cross-sectional association between blood pressure and end-organ damage is very weak in end-stage renal disease patients if the blood pressure values are "casual," but the relationship is much stronger when ambulatory blood pressure monitoring-derived measurements are used. One prospective study clearly linked the sustained loss of diurnal blood pressure fall with sleep with progressive left ventricular dilatation. Loss of circadian variation in blood pressure is associated with an increased mortality rate for dialysis patients and for diabetic patients, regardless of diabetes type. The combination of nondipping in renal impairment leads to a high mortality rate. Much more work is needed to dissect out the causes for abnormal diurnal blood pressure rhythm and attempt to modulate this parameter. Obstructive sleep apnea may be a promising target for intervention.

Non-dipping circadian blood pressure and renal impairment are associated with increased mortality in diabetes mellitus.

To assess the relevance of circadian blood pressure variation to future morbidity and mortality in patients with diabetes mellitus. A retrospective descriptive 4 year follow-up study of data collected after ambulatory blood pressure monitoring in a clinic setting. Seventy-five patients (46 male; 29 female) of whom 41 % had Type 1 diabetes and 59% Type 2 were followed up for a median of 42 months (11-56). The median creatinine for the whole group at baseline was 101 (56-501) micromol/l. The median circadian blood pressures for the total study population were 147 (110-194)/87 (66-109) mmHg during daytime and 132 (86-190)/77 (50-122) mmHg during night-time. Half of the patients exhibited a fall in night-time pressures to 10% lower than daytime pressures (dippers). Dippers were younger, 47 (32-75) years, than non-dippers, 57 (35-79) years, P = 0.03. Over time, dippers had a lower mortality than non-dippers, with 8% deaths in the cohort of dippers, 26% deaths in the cohort of non-dippers, P = 0.04. Cox regression analysis revealed significant contributions from age, duration of diabetes and baseline renal function to subsequent mortality in non-dippers. Analysing current degree of renal impairment and original dipper status together revealed that, of those patients whose creatinine remained normal, 7% of patients whose blood pressure dipped had subsequently died and 10% of non-dipping patients had died; of those patients whose creatinine unequivocally rose, 10% of dipping patients had died and 42% of non-dipping patients had died, P = 0.03 Loss of circadian variation in blood pressure is associated with an increased mortality rate, regardless of diabetes type. The combination of non-dipping and subsequent renal impairment leads to the highest mortality rate. The study suggests a role for ambulatory blood pressure monitoring in day-to-day clinical practice to select patients with nephropathy who are at greatest risk, in an effort to alter outcome.

Body temperature regulation in rats near term of pregnancy.

Experiments were carried out to define the effects of pregnancy on body temperature (Tb) regulation in rats. Tb was measured by biotelemetry in six animals from day 10 of pregnancy (term day 21) to postpartum day 10. Average 24-h Tb decreased from day 15 of gestation to the time of parturition. Furthermore, there was a loss of the normal circadian variation of Tb late in gestation, which was again present by postpartum day 2. The decrease in 24-h Tb on day 15 of gestation resulted from this loss of circadian variation, as Tb did not increase during the dark period. The further decrease in Tb on day 20 of gestation resulted from an overall decrease in Tb during the light and dark periods as well as from a loss of the circadian variation in Tb. Tb increased dramatically within 4 h of birth of the first pup, which always occurred on day 21 during the light period. The mechanisms responsible for these dramatic changes in thermoregulation during late gestation and around the time of parturition are presently unknown.

Importance of long-acting angiotensin-converting enzyme inhibitors for congestive heart failure

The renin-angiotensin system (RAS) has both localized and systemic effects in the pathophysiology of heart failure. These may lead to structural changes in the heart and blood vessels as well as to more disseminated symptomatology, including vasoconstriction and both satt and water retention. In association with other neurohormonal mechanisms, such as the sympathetic nervous system, these latter effects result in an elevated work load for the heart. The increase in neurohormonal activity, seen in some patients with heart failure, may result in a loss of circadian variation in heart rate and blood pressure and deprive the heart of a needed reduction in work load during the night. The suppression of such neurohormonal activity through the use of long-acting angiotensin-converting enzyme (ACE) inhibitors, such as lisinopril, provides a means of controlling such symptoms. In comparison with short-acting ACE inhibitors, such long-acting suppression of the RAS may have a number of advantages. These include a more sustained increase in exercise duration, improvement in left ventricular ejection fraction, and, speculatively, a better influence on patient mortality.

Is circadian variation in theophylline trough serum concentrations determined by time of dosing?

Ten healthy volunteers were each given two separate courses of eight doses of theophylline 200 mg as a slow release preparation at 12 hourly intervals. In the first course (regimen 1) the dose was given at 11.00 h and 23.00 h and in the second (regimen 2) at 05.00 h and 17.00 h. Sixty hours after the start of each course, four consecutive trough serum theophylline concentrations were measured. On regimen 1 the trough concentration of theophylline was 6.2 +/- 2.2 mg/l (mean +/- s.d.) at 11.00 h compared with 5.4 +/- 1.9 mg/l at 23.00 h (P less than 0.01). This circadian variation was abolished during regimen 2 when the mean theophylline concentrations were identical at 5.2 mg/l. The higher trough concentrations after the evening dose on regimen 1 and the loss of circadian variation on regimen 2 may be due to the change in sleep period in relation to the time of dosing.