Franca Carandente

From various kinds of heart rate variability to chronocardiology

Abstract We wish to show that cardiologic variability can be examined with benefit by the concepts and computer methods of chronobiology, the science (logos) of lifes (bios) time (chronos) structure. From heart rate data in a recent article, 1 dynamic end points are obtained to quantify health. 2 On a group basis, when conventional end points applied to 2 sets of electrocardiographic records fail to separate for sudden adult death, chronobiologic end points already do so. 2 Novel information not obtained by conventional location or dispersion indexes 3 can be provided by the computation of the circadian and other amplitudes. 4 Beyond sudden death after myocardial infarction, the importance of these amplitudes has been demonstrated in several additional cases of cardiologie interest 2 : (1) the amplitudes of several rhythmic components of systolic or diastolic blood pressure separate groups of human newborns with a positive versus negative family history of high blood pressure or cardiovascular diseases, or both, when the mean based on the same data does not do so; (2) in children ≥9 years old, the circadian amplitude and acrophase of blood pressure, but not the mean, separate groups at low or high risk of developing high blood pressure later in life; (3) at 15 years of age, the circadian amplitude of diastolic blood pressure, but not the mean, correlates with the thickness of the interventricular septum of the heart.

Chronobiometry with pocket calculators and computer systems

SummarySelected methods for the study of biologic time series are reviewed and their relative merits are discussed in the light of underlying assumptions. Their potential applications are exemplified in several fields of biology and medicine. The monitoring of environmental integrity, notably of pollution, is investigated. The need for specifying optimal sampling requirements is underlined. An individualized and time-qualified definition of health by the establishment of reference intervals is required for increasingly rational individualized program for the prevention and/or treatment of disease. With these reference intervals and rhythm characteristics available, one can better interpret with single samples or time series an increased risk of a certain disease or the inception of the disease. For all of these aims the monitoring of environmental and/or personal marker rhythms is essential — to obtain large data bases from which information can be more easily derived for monitoring personal health, to recognize risk as well as to diagnose disease early and to optimize treatment by timing according to rhythms.

Chronotype influences activity circadian rhythm and sleep: differences in sleep quality between weekdays and weekend.

Several studies have shown the differences among chronotypes in the circadian rhythm of different physiological variables. Individuals show variation in their preference for the daily timing of activity; additionally, there is an association between chronotype and sleep duration/sleep complaints. Few studies have investigated sleep quality during the week days and weekends in relation to the circadian typology using self-assessment questionnaires or actigraphy. The purpose of this study was to use actigraphy to assess the relationship between the three chronotypes and the circadian rhythm of activity levels and to determine whether sleep parameters respond differently with respect to time (weekdays versus the weekend) in Morning-types (M-types), Neither-types (N-types) and Evening-types (E-types). The morningness–eveningness questionnaire (MEQ) was administered to 502 college students to determine their chronotypes. Fifty subjects (16 M-types, 15 N-types and 19 E-types) were recruited to undergo a 7-days monitoring period with an actigraph (Actiwacth® actometers, CNT, Cambridge, UK) to evaluate their sleep parameters and the circadian rhythm of their activity levels. To compare the amplitude and the acrophase among the three chronotypes, we used a one-way ANOVA followed by the Tukey–Kramer post-hoc test. To compare the Midline Estimating Statistic of Rhythm (MESOR) among the three chronotypes, we used a Kruskal–Wallis non-parametric test followed by pairwise comparisons that were performed using Dunn’s procedure with a Bonferroni correction for multiple comparisons. The analysis of each sleep parameter was conducted using the mixed ANOVA procedure. The results showed that the chronotype was influenced by sex (χ2 with p = 0.011) and the photoperiod at birth (χ2 with p < 0.05). Though the MESOR and amplitude of the activity levels were not different among the three chronotypes, the acrophases compared by the ANOVA post-hoc test were significantly different (p < 0.001). The ANOVA post-hoc test revealed the presence of a significant difference (p < 0.001) between the M-types (14:32 h) and E-types (16:53 h). There was also a significant interaction between the chronotype and four sleep parameters: Sleep end, Assumed Sleep, Immobility Time and Sleep Efficiency. Sleep Efficiency showed the same patterns as did Assumed Sleep and Immobility Time: the Sleep Efficiency of the E-types was poorer than that of the M- and N-types during weekdays (77.9% ± 7.0 versus 84.1% ± 4.9 and 84.1% ± 5.2) but was similar to that measured in the M- and N-types during the weekend. Sleep Latency and Movement and Fragmentation Index were not different among the three chronotypes and did not change on the weekend compared with weekdays. This study highlights two key findings: first, we observed that the circadian rhythm of activity levels was influenced by the chronotype; second, the chronotype had a significant effect on sleep parameters: the E-types had a reduced sleep quality and quantity compared with the M- and N-types during weekdays, whereas the E-types reached the same levels as the other chronotypes during the weekends. These findings suggest that E-types accumulate a sleep deficit during weekdays due to social and academic commitments and that they recover from this deficit during “free days” on the weekend.

Blood pressure patterns in normal pregnancy and in pregnancy-induced hypertension, preeclampsia, and chronic hypertension

Objective To compare the 24-hour blood pressure (BP) pattern in physiologic pregnancy, pregnancy-induced hypertension, preeclampsia, and chronic hypertension. Methods We investigated four groups of women with singleton pregnancy: 73 controls, 48 patients with pregnancy-induced hypertension, 38 with preeclampsia, and 53 with mild to moderate chronic hypertension. The 24-hour BP monitoring was performed longitudinally in controls and in patients with chronic hypertension, and at the time of diagnosis in those with pregnancy-induced hypertension or preeclampsia. Results Nineteen thousand eight hundred seventy-two BP measurements were analyzed. In controls, the mean values of BP indices were lower than those first reported in nonpregnant women, and the acrophase was always localized in the first part of the afternoon. In pregnancy-induced hypertension and especially in preeclampsia, besides the obvious quantitative increase in BP, circadian BP oscillations were less pronounced than in controls, and the severity of hypertension seemed to favor the loss of diurnal rhythm. Conversely, in chronic hypertension, circadian oscillations were the same as in controls. Conclusion Standardized 24-hour BP monitoring during pregnancy allows quantitative and qualitative evaluations of the hypertensive status. However, if such a technique is used routinely in every clinical setting, we should establish specific thresholds of normality for pregnancy.

Circadian variations in expression of the trkB receptor in adult rat hippocampus

The expression of brain-derived neurotrophic factor (BDNF) in the central nervous system (CNS) and the expression of its high-affinity trkB receptor on neuron surfaces are known to depend on neuron activity. The expression of BDNF (mRNA and protein) and trkB mRNA shows circadian oscillations in rat hippocampal homogenates. We investigated circadian variations in trkB expression in specific areas of the adult rat hippocampal formation by immunohistochemistry. In sets of two experiments performed in the spring, 39 2-month-old male Wistar rats were accustomed to a 12-h light-12-h dark cycle for 2 weeks. Three animals were then sacrificed every 4 h. Forty-micrometer-thick coronal sections of hippocampal formation were obtained and processed for trkB immunohistochemistry. Cell staining intensity was assessed by image analysis of different hippocampal areas on five sections per animal. Circadian rhythmicity was evaluated by the cosinor method. Statistically significant circadian variations in trkB expression were found in dentate gyrus, entorhinal cortex, and the CA3 and hilar regions of the hippocampus, with highest expression during the first half of the dark (activity) period. These findings suggest a relationship between trkB expression and the physiological neuronal activation of wakefulness. TrkB receptor expression in the hippocampal regions studied was continuous and changes were gradual over the 24-h cycle, suggesting that more complex regulatory mechanisms also intervened.

Differential modulation of clock gene expression in the suprachiasmatic nucleus, liver and heart of aged mice

Studies on the molecular clockwork during aging have been hitherto addressed to core clock genes. These previous investigations indicate that circadian profiles of core clock gene expression at an advanced age are relatively preserved in the master circadian pacemaker and the hypothalamic suprachiasmatic nucleus (SCN), and relatively impaired in peripheral tissues. It remains to be clarified whether the effects of aging are confined to the primary loop of core clock genes, or also involve secondary clock loop components, including Rev-erbα and the clock-controlled genes Dbp and Dec1. Using quantitative real-time RT-PCR, we here report a comparative analysis of the circadian expression of canonical core clock genes (Per1, Per2, Cry1, Cry2, Clock and Bmal1) and non-core clock genes (Rev-erbα, Dbp and Dec1) in the SCN, liver, and heart of 3month-old vs 22month-old mice. The results indicate that circadian clock gene expression is significantly modified in the SCN and peripheral oscillators of aged mice. These changes are not only highly tissue-specific, but also involve different clock gene loops. In particular, we here report changes of secondary clock loop components in the SCN, changes of the primary clock loop in the liver, and minor changes of clock gene expression in the heart of aged mice. The present findings outline a track to further understanding of the role of primary and secondary clock loop components and their crosstalk in the impairment of circadian output which characterizes aging.

Circadian rhythmicity of acid secretion and electrical function in intact and injured rat gastric mucosa--the relation of timing to ulcerogenesis.

Alteration of electrical function in mammalian gastric mucosa is considered as an indicator of gastric barrier rupture. Measurements of transmucosal potential difference (PD) and electrical resistance (R) have documented such alterations to a variety of mucosal damaging agents. This study was designed to test whether the rat gastric mucosa exhibits circadian rhythms in acid secretion and electrical function and whether the damage produced by a mucosal acting agent (butyric acid) is also circadian-stage dependent. Mucosa was isolated from the gastric body of male rats standardized from birth to a light-dark regimen. Circadian rhythms of acid secretion and PD and R with acrophases during the dark hours were documented. Administration of butyric acid produced circadian-stage dependent damage with an acrophase also during the dark-phase span. Thus, in this experimental model, measurements of electrical function represented a poor index of gastric mucosal susceptibility to damaging agents. The authors discuss the possibility that rhythms other than those related to electrical function may better define mucosal vulnerability to ulcerogenesis.

Sleep quality and high intensity interval training at two different times of day: A crossover study on the influence of the chronotype in male collegiate soccer players

ABSTRACT The influence of the chronotype on the sleep quality in male collegiate soccer players in response to acute high intensity interval training (HIIT) performed at two different times of day was evaluated. The sleep quality was poorer in the morning-type than in the evening-type players after the evening HIIT session, whereas no significant changes in the sleep quality of the two chronotypes after the morning HIIT session was observed. The results suggest that an athlete’s chronotype should be taken into account when scheduling training sessions and to promote faster recovery processes.

Protective Effect of Aerobic Physical Activity on Sleep Behavior in Breast Cancer Survivors

Hypotheses. Sleep disorders are associated with an increased risk of cancer, including breast cancer (BC). Physical activity (PA) can produce beneficial effects on sleep. Study design. We designed a randomized controlled trial to test the effect of 3 months of physical activity on sleep and circadian rhythm activity level evaluated by actigraphy. Methods. 40 BC women, aged 35-70 years, were randomized into an intervention (IG) and a control group (CG). IG performed a 3 month of aerobic exercise. At baseline and after 3 months, the following parameters were evaluated both for IG and CG: anthropometric and body composition measurements, energy expenditure and motion level; sleep parameters (Actual Sleep Time-AST, Actual Wake Time-AWT, Sleep Efficiency-SE, Sleep Latency-SL, Mean Activity Score-MAS, Movement and Fragmentation Index-MFI and Immobility Time-IT) and activity level circadian rhythm using the Actigraph Actiwatch. Results. The CG showed a deterioration of sleep, whereas the IG showed a stable pattern. In the CG the SE, AST and IT decreased and the AWT, SL, MAS and MFI increased. In the IG, the SE, IT, AWT, SL, and MAS showed no changes and AST and MFI showed a less pronounced change in the IG than in the CG. The rhythmometric analysis revealed a significant circadian rhythm in two groups. After 3 months of PA, IG showed reduced fat mass %, while CG had improved weight and BMI. Conclusion. Physical activity may be beneficial against sleep disruption. Indeed, PA prevented sleep worsening in IG. PA can represent an integrative intervention therapy able to modify sleep behaviour.

Physical activity and breast cancer

Knowledge of the relationships between risks and benefits of a given lifestyle is fundamental to being able to change life-long habits responsible for the development of pathological processes. Breast cancer is a widely studied pathology of vast social importance. It is important to identify the most appropriate lifestyle to give the organism the necessary tools to prevent tumour development. Physical exercise can act on and modify the different risk factors responsible for the development of both the primary pathology of breast cancer and relapses, thus reducing mortality. The various hypotheses of the biological routes through which physical activity can reduce risk indicate involvement of the following mechanisms: reduction in body weight, reduction in circulating levels of sex hormones, reduction in insulin resistance, reduction in leptin and adiponectin and modulation of the immune system. Recent discoveries on the mechanisms of cancer development indicate that cancer is the chronic pathology par excellence, and it is highly unlikely that it will be possible to eliminate it by concentrating all our efforts on tumour treatment techniques alone; it will be necessary to cure the whole organism in depth. Physical activity can be considered an “anticancer biology” that succeeds in exploiting the breakthroughs of medicine and our natural defences.