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Biomedical subjects

Franz Halberg

Publications and source records attributed to Franz Halberg.

At least 55 records · Page 3Linked to original sources

Effects of diaphragmatic breathing on ambulatory blood pressure and heart rate.

Psychological procedures, such as self-hypnosis in the form of autogenic training, have been proposed for correcting a deviant, e.g., high blood pressure (BP). In view of the overwhelming evidence for the circadian (CD) stage dependence of any treatment effects, the CD stage dependence of the effects of diaphragmatic breathing (DB) on BP and heart rate (HR) was explored in data from a clinically healthy normotensive subject who, following 3 weeks of ambulatory monitoring as a reference standard, measured BP and HR with a manual monitor at 1-min intervals for 5 min before and after DB (three deep diaphragmatic breaths) and who performed DB for about 2 weeks at about 2-h intervals while awake. The 3-week data series were analyzed by cosinor, involving the least-squares fit of cosine curves with periods of 24, 12 and 168 h. A CD rhythm was detected for BP and HR (P < 0.001 in each case), peaking in the afternoon. Some about-weekly (circaseptan; CS) BP rhythms and 12-h (circasemidian) components were also statistically significant. DB was found to reduce systolic (S) BP. Overall, SBP decreased by 5.9 +/- 0.8 mmHg (P < 0.001) and diastolic (D) BP by 1.4 +/- 0.8 mmHg (P < 0.005), while HR remained at about the same average. The effect of DB on BP was CD-dependent, the largest response occurring in the afternoon, 2-3 h before the peaks in SBP and DBP found in the reference data of the same subject. There was also a 5-10% decrease in SBP around the weekend (Friday, Saturday and Sunday). The results on a single subject suggest the need to collect similar data on others for optimizing by clock-hour, day of the week, and eventually by the marker rhythms BP and/or HR the best times for DB and other procedures. The personalized best time for people on different work/rest schedules for relaxation may be several hours before their BP has reached its highest point in the 24-h span. HR may serve as a marker for DB timing, but the effect on HR of DB was only of borderline statistical significance in the subject investigated.

Adolescent↗

Toward chronocardiologic and chronomic insights: dynamics of heart rate associated with head-up tilting.

As a step towards investigating the chronome (i.e. the inferential endpoints of chaos, trends and rhythms) of heart rate (HR) variability (HRV), we investigated whether the fractality or complexity of HRV is affected by a head-up tilting (HUT) test in the morning after an overnight fast. Spectral and non-linear analyses of HR were performed on data gathered during an 80 degrees passive HUT test in 15 men and 28 women 32.8 +/- 11.5 years of age. The non-linear endpoints included the scaling exponents alpha1 (<11 beats) and alpha2 (>11 beats), which indicate fractal properties, calculated with detrended fluctuation analysis, and the approximate entropy (ApEn), a measure of overall complexity. Passive HUT increased alpha1 (from 0.986 +/- 0.217 to 1.370 +/- 0.185; P = 0.0001), but did not alter alpha2 (from 0.925 +/- 0.110 to 0.958 +/- 0.130; P = 0.19). A slight but statistically significant decrease in ApEn was seen during HUT (from 1.114 +/- 0.131 to 1.013 +/- 0.197; P = 0.002). In the tilt-up position, there was a statistically significant negative correlation between alpha1 and ApEn (r = -0.490; P < 0.05). In both the supine and the tilt-up position, alpha1 was correlated weakly with HF (r = -0.343 and r = -0.322, respectively), and strongly with LF/HF (r = 0.557 and r = 0.795), respectively. There was also a negative correlation between ApEn and LF/HF (r = -0.406 and r = -0.357, respectively). alpha2 did not correlate with any spectral or non-linear measures of HRV. Short-term fractal properties and complexity of HR were lowered with orthostatic stress. Alterations of the autonomic activities could be partly responsible for these changes and await extension of such studies to assess the broad spectral element of HRV, that includes, with components of approximately 3.6 and approximately 10.5 s, cycles with very much lower frequencies, along the scales of hours and even years, that critically modulate the mislabeled (only relatively high- and low-frequency) components in the range of seconds or minutes.

Adult↗

Stress/strain/life revisited. Quantification by blood pressure chronomics: benetensive, transtensive or maletensive chrono-vasculo-neuro-immuno-modulation.

We propose to initiate the automatic self-assessment of wear and tear as "stress and strain" by the time structures of blood pressure (BP) and heart rate (HR), in order to arrive eventually at an individualized timely and timed routine of life and to early preventive intervention as soon as needed. The routine may involve physiological scheduling of physical and mental activities and meals, and if need be of non-drug or drug treatment for stress amplification, e.g., by exercise, and/or strain (not stress) relief by relaxation. In so doing, we recognize the circulation as a pillar and marker of preventive and active neuroimmunomodulation (NIM), suggesting that some concerns of a vasculo- and broader NIM can be quantified by transdisciplinary chronobiology using its cartography--chronomics--of time structures, i.e., chronomes, from chronos = time and nomos = rule. Thus, we are introducing the chronomics of BP, HR and of other variables in the historical context of pioneers who were indispensable to experimental medicine. We build upon their contributions, but we must point out when, in the past, by necessity rather than choice, the giants provided rationalizing truisms that are no substitute for systematic serial data collection and appropriate computer analysis. A time-unspecified spotcheck as a baseline is much better than no measurement, but very often it is not enough, and it is always insufficient when an estimate of variability constitutes the information needed. For dynamic cycles, there are only reference cycles as a routine, although when maps are available, single timed spotchecks can be invaluable. With reference to their historical context, here we rely only upon data which necessity, rather than philosophy, compels us to collect.

Activities of Daily Living↗

Transient circadian hyper-amplitude-tension (CHAT) may be intermittent: case reports illustrating gliding spectral windows.

Taking the heart rate (HR) for one cycle, whether to examine behavior in the region of periods of 1 s, 1 day, 1 week, 1.3 or 10.5 years, etc., is hazardous. Replications, when possible are mandatory for examining altered variability, whatever the period(s) involved may be. This replication in the individual, and across individuals when the periods are long, measured in decades, may serve for diagnosis and treatment. This rule applies in particular to a seemingly transient circadian hyper-amplitude-tension (CHAT), an over peer-threshold variability in blood pressure (BP), based on the fit of a 24-h cosine curve to time series of appropriate length, rather than to a mere snapshot covering just a single day or week. Transient CHAT may turn into intermittent CHAT, as determined in two cases presented herein. One case of transient CHAT could be so named after a successful treatment (Rx) change eliminated CHAT as an effect validated by monitoring at 30-min intervals for a 7-day span on a new treatment. CHAT disappeared for over 300 consecutive half-hourly measurements, but thereafter it reappeared. During the ensuing nearly continuously monitored 5 years, CHAT continued to appear and disappear sometimes without a treatment change. In another case, which was responsive to a change in the timing of medication, CHAT also disappeared and thereafter reappeared. In a short-term perspective of weeks or months of monitoring, CHAT seemed to be transient, but further monitoring again revealed it to be intermittent. Cases of intermittent CHAT require follow-up for outcomes by comparison with the population at large. Miniaturized instrumentation for their detection should be a high priority, but it must be realized that the automatic ambulatorily functioning monitors, available at 10% of the regular price through a BIOCOS project (corne001@umn.edu), already signify great progress, as compared to previously used manual measurements made around the clock by hypertensive opinion leaders in medicine from diagnosis to death. On automatically collected time series of BP and HR, gliding pergressive spectral windows as such, or such pergressive windows aligned further with global spectral windows, visualize the changing dynamics involved in health and disease, in the steps of Werner Menzel and Paolo Scarpelli.

Aged↗

Chronoecoepidemiology of "strain": infradian chronomics of urinary cortisol and catecholamines during nightly exposure to noise.

This meta-analysis of published data (Noise Health 5 (2002) 35 and 47) summarizing a survey for 40 days of the nightly excretion of urinary free cortisol, epinephrine and norepinephrine validates a circaseptan cortisol pattern anticipated and reported earlier for cortisol, here not detected for the catecholamines. We also quantify a circadecan (about 10-day) variation in nightly norepinephrine excretion, but not in the excretion of the other two hormones examined. About 4.2-day variations, common to norepinephrine and epinephrine, and an about 4.7-day variation in cortisol await further scrutiny, since these components were not anticipated. Infradian characteristics are quantified time-microscopically and differences among infradian aspects of the spectral element of endocrine chronomes (time structures; from chronos, time and nomos, rule) are demonstrated. Chronomics, the cartography of chronomes, reveals that "stress hormones" need to be examined separately in a budding chronoepidemiology seeking to detect how humans interact, mostly for better, sometimes for worse, with the undesirable features of the technology they create and of its consequences, such as aircraft noise.

Activity Cycles↗

Blood pressure self-surveillance for health also reflects 1.3-year Richardson solar wind variation: spin-off from chronomics.

Self-experimentation concerns not only scientists, but also each individual for the sake of his/her chronobiologic health and science literacy, eventually to be acquired in primary and secondary education. Public education ensures that everybody who knows how to read or write can dispense with the service of a costly scribe. At all ages, public education can teach equally well how to find out whether one's blood pressure (BP) and heart rate (HR) responds to an increase in sodium intake with a rise, with no change or with a decrease in BP. This task and many others could become a matter of informed self-surveillance. Whenever there are inter-individual, sometimes opposite differences in response, government-sponsored trials on groups that do not consider such differences cannot solve what only the individual can do, at first by help from schools. Eventually special institutions may be designed for chronomics, the monitoring, interpretation and archivization of chronomes (time structures; from chronos = time and nomos = rule) of biological variables, also charged with a demographic analyzing and reporting system. Each individual's properly coded record, to guard confidentiality, becomes part of a promptly accessible database for one's own needs and for society's requirements. What individuals and small groups started as chronobiology, what is immediately available on back burners, as a service by an international project on the biosphere and the cosmos (BIOCOS) (corne001@umn.edu) could become a public system of planned surveillance archivization of one's rhythms from womb to tomb. Alterations of a rhythm's amplitude or acrophase or of a deterministic or other chaotic endpoint, such as a correlation dimension and approximate entropy, or of a standard deviation, among a multitude of other endpoints, can signal (in the otherwise neglected normal range) reversible risk elevations. If these elevated risks are detected and prompt the institution of countermeasures, such prehabilitation can save the cost of rehabilitation or of long-term care after morbid events; suffering also can be prevented such as that by those who are unlucky enough to helplessly survive a massive brain, heart or societal "stroke". As an equally important dividend, science gains in basic and applied terms, as illustrated herein by the demonstration of a trans-year, an approximately 1.3 to 1.6-year, heretofore unknown component of the human BP and HR spectrum, beating with the circannual component and characterizing the same data. Chronomically interpreted self-monitoring is a civic duty for both one's health and everybody's science.

Blood Pressure Monitoring, Ambulatory↗

Circadian heart rate and blood pressure variability considered for research and patient care.

OBJECTIVES: To review mechanisms of circadian variations in heart rate variability (HRV) and blood pressure variability (BPV) and mortality and morbidity due to cardiovascular diseases (CVD). METHODS: Results from 7-day/24-h HRV and BPV are interpreted by gender and age-specified reference values in the context of a Medline search. RESULTS: Abnormal HRV and BPV measured around the clock for 7 days provides information on the risk of subsequent morbid events in subjects without obvious heart disease and without abnormality outside the conventional (in the sense of chronobiologically unquantified) physiological range. Meditation, beta-blockers, ACE inhibitors, n-3 fatty acids and estrogens may have a beneficial influence on HRV, but there is no definitive outcome-validated therapy. Low HRV has been associated with a risk of arrhythmias and arrhythmic death, unstable angina, myocardial infarction, progression of heart failure and atherosclerosis. BPV may be characterized by treatable circadian-hyper-amplitude-tension (CHAT), which can be transient '24-h CHAT' or '7-day-CHAT', MESOR-hypertension and/or an unusually-timed (odd) circadian acrophase (ecphasia), all associated with an increased risk of stroke, stroke death, myocardial infarction, and kidney disease. CONCLUSIONS: Precise insight into the patho-physiology in time of HRV and BPV is needed with development of a consensus on best measures of HRV for clinical purposes and to determine when a 7-day record interpreted chronobiologically suffices and when it does not, for detection within as well as outside the conventional normal range, for diagnostic clinical practice and to direct therapy of risk greater than that associated with hypertension, smoking or any other risk factor.

Blood Pressure↗

Circadian telomerase activity and DNA synthesis for timing peptide administration.

DNA synthesis and telomerase activity were assessed in nude mice transplanted with hepatic carcinoma. Hepatic cancer cells (SMMC-7721) were implanted into both flanks of each of 14 BALB/C mice synchronized in 12 h of light alternating with 12 h of darkness (LD12:12) for 4 weeks. At 7 timepoints, tumor samples were collected for measurement of cellular DNA content by flow cytometry and telomerase activity by PCR-ELISA assay. Cosinor analyses determine a 24-h rhythm for all variables, showing a similar timing for the DNA-synthesis phase and telomerase activity. These results provide a model for exploring optimal timing of chronotherapy with peptides, especially for treatment with telomerase inhibitors.

Animals↗

Effects of autogenic training and antihypertensive agents on circadian and circaseptan variation of blood pressure.

Even when the daily blood pressure mean is acceptable, too large a circadian amplitude of blood pressure largely increases cardiovascular disease risk. Autogenic training (N = 11), a non-pharmacologic intervention capable of lowering an excessive blood pressure variability, may be well-suited for MESOR-normotensive patients diagnosed with circadian-hyper-amplitude-tension (CHAT). Not all anti-hypertensive drugs affect blood pressure variability. Accordingly, long-acting carteolol (N = 11) and/or atenolol (N = 8) may be preferred to captopril retard (N = 13), nilvadipine (N = 8), or amlodipine (N = 7) for midline-estimating statistic of rhythm (MESOR)-hypertensive patients with CHAT. Prospective outcome studies are needed to assess whether the relative merits of these treatments are in keeping with their effects on blood pressure and blood pressure variability.

Antihypertensive Agents↗

Approximate entropy of human respiratory movement during eye-closed waking and different sleep stages.

STUDY OBJECTIVE: The breath-to-breath variability of respiratory parameters changes with sleep stage. This study investigates any alteration in the approximate entropy (ApEn) of respiratory movement as a gauge of complexity in respiration, by stage of consciousness, in the light of putative brain interactions. PARTICIPANTS: Eight healthy men, who were between the ages of 23 and 29 years, were investigated. MEASUREMENTS AND RESULTS: The signals of chest wall movement and EEG were recorded from 10:30 PM to 6:00 AM. After analog-to-digital conversion, the ApEn of respiratory movement (3 min) and EEG (20 s) were computed. Surrogate data were tested for nonlinearity in the original time series. The most impressive reduction in the ApEn of respiratory movement was associated with stage IV sleep, when the ApEn of the EEG was also statistically significantly decreased. A statistically significant linear relation is found between the ApEn of both variables. Surrogate data indicated that respiratory movement had nonlinear properties during all stages of consciousness that were investigated. CONCLUSION: Respiratory movement and EEG signals are more regular during stage IV sleep than during other stages of consciousness. The change in complexity described by the ApEn of respiration depends in part on the ApEn of the EEG, suggesting the involvement of nonlinear dynamic processes in the coordination between brain and lungs.

Adult↗

System times and time horizons for biospheric near-matches of primarily non-photic environmental cycles.

System time is defined as the duration (T) and sampling density (deltat) of a given study. A time horizon is obtained by combining analytical results on endpoints of time structures (chronomes), usually on control groups, from accumulating diverse studies carried out with drastically different values of T and deltat. These two design considerations depend upon and are limited by resources. The desideratum of a small At e.g., for studies of chaotic endpoints, limits T, e.g., has thus far precluded a continuous mapping of decadal cycles in endpoints such as the approximate entropy or the correlation dimension. Time horizons are being documented for an increasing number of variables that undergo cycles with infra-annual frequencies - with one cycle in about one, two and/or five decades - in the biosphere as in the environment. These infra-annuals, in and around us, modulate ultra-annuals, including circadians, as well as about 7-day (circaseptan) and about half-yearly (circasemiannual) cycles, all prominent, e.g., in geophysical and biospheric specta. Neglect of infra-annual chronomics can lead to blunders. A statistically highly significant decrease in the excretion of steroidal metabolites (or in heart rate variability) may be misinterpreted as premature aging if it lasts for several years, and may be unnecessarily acted upon, e.g., by drugs. The decrease, however, may only be transient, occurring only during a given stage of a circadecadal cycle, and it may be followed for the next several years by an also spurious "rejuvenation", possibly misinterpreted as a drug effect. When recognized as the alternating stages of decadal cycles and assessed with an affordable deltat, infra-annuals of variables involved in major problems of our day, including homicides and wars, may lead us to manipulable internal or external mechanisms, and thus, eventually, possibly to countermeasures to crime and terror as well as to the optimization of aims such as spirituality.

Circadian Rhythm↗

Marriage and divorce over a century in Japan: social biomedicine, not yet societal therapy.

During the past half-century, the differences found in the spectral element of marriages vs. divorces in Tokyo reveal a half-year aspect which increasingly dominates in marriages, probably as a result of a mix of socio-economic, climatic and/or geomagnetic, as well as human affection-related factors, On the other hand, a decadal component is prominent in divorces, possibly in association with non-photic solar activity. Sparser (yearly, not monthly) records, obtained over a century at different latitudes in Japan, demonstrate that the decadal components are not consistent in moving spectra of original (as yet not detrended) data. Longer and denser series over much greater differences in latitudes and longitudes will have to be subjected to a much more thorough scrutiny, in conjunction with a series of possibly pertinent variables, to assess the contributions of different sources of variation in different areas of Japan and world wide, preferably in democratic, non-combatant areas, where the socio-economical, political and other war-associated conditions are mostly in the background.

Confidence Intervals↗

Geomagnetics and society interact in weekly and broader multiseptans underlying health and environmental integrity.

Evidence for the ubiquity and partial endogenicity of about-weekly (circaseptan) components and multiples and/or submultiples thereof (the multiseptans) accumulates as longer and denser records become available. Often attributed to a mere response to the social schedule, circaseptan components now have been documented to characterize environmental variables related to primarily non-photic solar effects. Plausibly, like circadians, circaseptans are anchored in genomes, from bacteria to humans, via both an internal and external evolution. If so, circaseptans, like circadians, may be found in the absence of a 7-day schedule, whereas the social schedule may play a synchronizing role and be responsible for the detection of prominent weekly variations in population statistics. The wobbliness of multiseptans and other components of some environmental time structures (chronomes) may correspond to the wobbliness of multiseptans found in cardiovascular morbidity statistics. Here, the latter stem primarily, but not exclusively, from an extensive database on the incidence of daily calls for an ambulance in Moscow, Russia from 1979-1981. A modulation of multiseptans and other chronome components of both environmental and biological variables by the about 11-year solar activity cycle (and of other low-frequency signals reviewed elsewhere) may account for prior controversies and scepticism about a variety of non-photic effects on biota. This is notably the case when relatively short series are analyzed without consideration of effects of unassessed long-term variations; this is the task of the new field of chronomics. In the spectral element of the chronomes of geophysical and biospherical variability, there are natural near weeks,apart from any precise 7-day periodicity.

Analysis of Variance↗

Partial spectral element in the chronome of a human neonatal heart rate at term.

An initial infradian prominence characterizes the spectral element of the chronome or the time structure of half-hourly heart rates during the first 40 days after birth of a boy born at term. Immediately pertinent infradian prominence, which was previously documented for many premature infants and anticipated from the integration of 2-day segments of half-hourly data from infants born at term, is now displayed longitudinally. Dominating first are an about-weekly (circaseptan) or half-weekly (circasemiseptan) and an about 26-day (circatrigintan) component, with a subsequent change from infradian to circadian prominence.

Chronobiology Phenomena↗

Circadian blood pressure overswinging in a physically fit, normotensive African American woman.

Ambulatory blood pressure (BP) and heart rate (HR) were measured in a physically fit, normotensive postmenopausal African American woman, before and after 15 weeks of aerobic training. Mean BP, HR, and HR variability were normal at the outset and were further improved by training. Training had no effect on circadian BP variation, which exceeded gender- and age-specified limits, indicative of circadian hyperamplitude tension (CHAT). A 12-week treatment with the beta1-adrenoceptor blocker atenolol, 14 months post-training, normalized CHAT and HR variability and further reduced BP and HR. These results suggest beta1-adrenergic mediation of CHAT and its refractoriness to exercise training.

Adrenergic beta-Antagonists↗