Metronomic Breathing Research Articles

Valsalva manoeuvre in patients with different Parkinsonian disorders

The valsalva manoeuvre (VM), used as an autonomic function test, can detect sympathetic and/or parasympathetic autonomic dysfunction. This study investigated the value of VM in patients with different Parkinsonian syndromes (PS). We continuously recorded blood pressure, ECG and respiration among 38 patients with multiple system atrophy (MSA), 32 patients with progressive supranuclear palsy (PSP), 26 patients with idiopathic Parkinson's disease (PD) and in 27 healthy subjects matched in age and sex (Con). VM was performed in addition to metronomic breathing and tilt-table testing. VM could not be analysed in 26% of the ES patients. Valsalva ratio (VR), as a parameter of cardiovagal function, was pathologically decreased in all patient groups. Valsalva ratio (VR) was not able to discriminate parasympathetic dysfunction between patients and controls as well as E/I ratio of metronomic breathing. As a parameter of sympathetic dysfunction during VM, the physiological increase of blood pressure was more often missing during phase IV than phase II especially in PD and MSA patients. Correlation with orthostatic hypotension during tilt-table testing was only moderate. Although VM can demonstrate sympathetic and parasympathetic autonomic dysfunction, we cannot recommend VM as a first line autonomic test in PS patients. Metronomic breathing and tilt-table test seem more capable as parasympathetic resp. and sympathetic function tests to identify cardiovascular abnormalities in PS patients.

The Effects of Sildenafil on Heart Rate Variability in Healthy Subjects

The effects of sildenafil on heart rate variability were investigated in 20 healthy male subjects aged 24 (21 to 32) years (median; range). Subjects orally received single 100-mg doses of sildenafil and placebo under randomized double-blind crossover conditions on 2 separate study days. Time domain measures of heart rate variability were assessed under conditions of relaxed rest, metronomic breathing (6 cycles per minute), and bicycle ergometry before administration of sildenafil and placebo as well as 60 minutes afterwards. Sildenafil did not alter heart rate nor heart rate variability to a significant extent (P > 0.05).

Hypohydration and prior heat stress exacerbates decreases in cerebral blood flow velocity during standing

Hypohydration is associated with orthostatic intolerance; however, little is known about cerebrovascular mechanisms responsible. This study examined whether hypohydration reduces cerebral blood flow velocity (CBFV) in response to an orthostatic challenge. Eight subjects completed four orthostatic challenges (temperate conditions) twice before (Pre-EU and Pre-Hyp) and following recovery from passive heat stress ( approximately 3 h at 45 degrees C, 50% relative humidity, 1 m/s air speed) with (Post-EU) or without (Post-Hyp) fluid replacement of sweat losses (-3% body mass loss). Measurements included CBFV, mean arterial pressure (MAP), heart rate (HR), end-tidal CO(2), and core and skin temperatures. Test sessions included being seated (20 min) followed by standing (60 s) then resitting (60 s) with metronomic breathing (15 breaths/min). CBFV and MAP responses to standing were similar during Pre-EU and Pre-Hyp. Standing Post-Hyp exacerbated the magnitude (-28.0 +/- 1.4% of baseline) and duration (9.0 +/- 1.6 s) of CBFV reductions and increased cerebrovascular resistance (CVR) compared with Post-EU (-20.0 +/- 2.1% and 6.6 +/- 0.9 s). Standing Post-EU also resulted in a reduction in CBFV, and a smaller decrease in CVR compared with Pre-EU. MAP decreases were similar for Post-EU (-18 +/- 4 mmHg) and Post-Hyp (-21 +/- 5 mmHg) from seated to standing. These data demonstrate that despite similar MAP decreases, hypohydration, and prior heat stress (despite apparent recovery) produce greater CBFV reduction when standing. These observations suggest that hypohydration and prior heat stress are associated with greater reductions in CBFV with greater CVR, which likely contribute to orthostatic intolerance.

Right ventromedial prefrontal lesions result in paradoxical cardiovascular activation with emotional stimuli

Ventromedial prefrontal cortex (VMPFC) lesions can alter emotional and autonomic responses. In animals, VMPFC activation results in cardiovascular sympathetic inhibition. In humans, VMPFC modulates emotional processing and autonomic response to arousal (e.g. accompanying decision-making). The specific role of the left or right VMPFC in mediating somatic responses to non-arousing, daily-life pleasant or unpleasant stimuli is unclear. To further evaluate VMPFC interaction with autonomic processing of non-stressful emotional stimuli and assess the effects of stimulus valence, we studied patients with unilateral VMPFC lesions and assessed autonomic modulation at rest and during physical challenge, and heart rate (HR) and blood pressure (BP) responses to non-stressful neutral, pleasant and unpleasant visual stimulation (VES) via emotionally laden slides. In 6 patients (54.0 +/- 7.2 years) with left-sided VMPFC lesions (VMPFC-L), 7 patients (43.3 +/- 11.6 years) with right-sided VMPFC lesions (VMPFC-R) and 13 healthy volunteers (44.7 +/- 11.6 years), we monitored HR as R-R interval (RRI), BP, respiration, end-tidal carbon dioxide levels, and oxygen saturation at rest, during autonomic challenge by metronomic breathing, a Valsalva manoeuvre and active standing, and in response to non-stressful pleasant, unpleasant and neutral VES. Pleasantness versus unpleasantness of slides was rated on a 7-point Likert scale. At rest, during physical autonomic challenge, and during neutral VES, parameters did not differ between the patient groups and volunteers. During VES, Likert scores also were similar across the three groups. During pleasant and unpleasant VES, HR decreased (i.e. RRI increased) significantly whereas BP remained unchanged in volunteers. In VMPFC-L patients, HR decrease was insignificant with pleasant and unpleasant VES. BP slightly increased (P = 0.06) with pleasant VES but was stable with unpleasant VES. In contrast, VMPFC-R patients had significant increases in HR and BP during pleasant and not quite significant HR increases (P = 0.06) with only slight BP increase during unpleasant VES. Other biosignals remained unchanged during VES in all groups. Our results show that VMPFC has no major influence on autonomic modulation at rest and during non-emotional, physical stimulation. The paradoxical HR and BP responses in VMPFC-R patients suggest hemispheric specialization for VMPFC interaction with predominant parasympathetic activation by the left, but sympathetic inhibition by the right VMPFC. Valence of non-stressful stimuli has a limited effect with more prominent left VMPFC modulation of pleasant and more right VMPFC modulation of unpleasant stimuli. The paradoxical sympathetic disinhibition in VMPFC-R patients may increase their risk of sympathetic hyperexcitability with negative consequences such as anxiety, hypertension or cardiac arrhythmias.

Calculating sympathovagal balance from heart rate variability: are there alternatives in adolescents?

Objective — Assessing sympathovagal balance by calculating LF/HF-ratio from power spectral analysis (PSA) of heart rate variability (HRV) may be difficult in adolescents as chaotic breathing leads to methodical bias and metronomic breathing is not easy to perform. Diastolic blood pressure variability (dBPV) is less influenced and may therefore offer more stable values for calculations. The present study was performed on 72 paediatric subjects to investigate possible alternative LF/HF-calculations from PSA of HRV and dBPV.Methods and results — Seventy-two paediatric individuals in three groups: 12 controls, 17 heartand heart-lung-transplanted children (TX) and 43 adolescents born small for gestational age (SGA). Short-term beat-to-beat HRV and BP-recordings were made supine and during active standing. Ratios calculated: LF/HF from HRV, LF/HF from dBPV, LF-dBPV/HF-HRV and LF-HRV/HF-dBPV. LF/HF from dBPV as well as LF-HRV/HF-dBPV did not correlate with LF/HF-HRV. Correlation of LF/HF from HRV and LF-dBPV/HF-HRV was high especially in TX and in patients with resting heart rate of above 90 beats per minute.Conclusions — In adolescents, the ratio of LF-dBPV/HF-HRV may be an alternative method for calculating sympathicovagal balance being less influenced by breathing patterns. In younger patients with elevated resting heart rate, but also in patients with very low HRV such as TX-patients this method could be a supplemental diagnostic tool whenever autonomic nervous control on the cardiocirculatory system has to be assessed.

Hypohydration Exacerbates Decreases in Cerebral Blood Flow Velocity During Orthostatic Stress

PURPOSE: Hypohydration is associated with orthostatic intolerance, however little is known about cerebrovascular mechanisms responsible. This study examined if hypohydration reduces cerebral blood flow velocity (CBFV) in response to an orthostatic challenge. METHODS: Eight subjects completed four orthostatic challenges (temperate conditions) twice before (PRE-EU) and after passive heat stress (∼3h @ 45°C, 50% rh, 1m/s air speed) with (POST-EU) or without (POST-HYPO) fluid replacement of sweat losses (−3% body mass loss). Measurements included CBFV, blood pressure (BP), heart rate (HR), end-tidal CO2(ETCO2), rectal (Trec) and skin (Tsk) temperatures, included being seated (20 min) followed by standing (60 sec) then re-sitting (10 min) with metronomic breathing (15 breaths/ min). RESULTS: Two PRE-EU results were similar. Standing when POST-HYPO resulted in greater CBFV reductions (P<0.05), greater HR increases (P<0.05), but similar BP decreases than when standing during PRE-EU and POST-EUH. POST-HYPO Trec was higher (P<0.05), but Tskand ETCO2were similar to POST-EU and PRE-EU. CONCLUSIONS: These data demonstrate that despite similar BP responses, hypohydration causes a greater CBFV reduction when standing which provides a mechanism for increased risk of orthostatic hypotension.

Acute effects of caffeine on heart rate variability in habitual caffeine consumers

During the last years, heart rate variability (HRV) has become a promising risk factor for cardiovascular events. However, the effect of caffeine on HRV in habitual caffeine consumers has barely been investigated. Therefore, we treated 30 male habitual caffeine users in a randomized double-blinded crossover study design with either placebo, 100 or 200 mg caffeine orally and determined parameters of HRV under resting conditions and metronomic breathing. As result, we could not detect significant differences in HRV parameters up to 90 min after drug ingestion. We conclude that modest amounts of caffeine do not reveal negative nor positive effects on HRV within the first 90 min after drug ingestion in young and healthy habitual caffeine consumers. However, further research is necessary to determine the effects of caffeine on HRV in habitual caffeine users, healthy as well as suffering from diabetes, hypertension and postmyocardial infarction.

Cardiorespiratory Regulation in Migraine. Results in Children and Adolescents and Review of the Literature

To investigate autonomic regulation in juvenile migraine we studied 70 children and adolescents with migraine during the headache-free period and 81 healthy controls by cardiorespiratory function tests. Heart rate variability was analysed with time and frequency domain indices during spontaneous breathing at rest and during metronomic breathing. Changes of heart rate and blood pressure were studied during tilt-table test, active standing, Valsalva manoeuvre and sustained handgrip. We found significant differences in metronomic breathing, tilt-table test and Valsalva manoeuvre. We interpret our findings and results reported in the literature as pointing to a restricted ability of the system to rest, which supports therapies intending to further this ability. In autonomic tests, hyperreactivity in juvenile migraineurs changes to hyporeactivity and passive coping in adults. This might be explained by disturbances of raphe nuclei and the periaqueductal grey. It corresponds to psychological findings in juvenile migraineurs reporting hypersensitivity and repressed aggression and claiming learned helplessness.

Erectile dysfunction--value of neurophysiologic diagnostic procedures

Neurogenic, particularly autonomic disorders, frequently contribute to the etiology and pathophysiology of erectile dysfunction. Parasympathetic and sympathetic outflow mediates erection. Noncholinergic, nonadrenergic neurotransmitters induce activation of cyclic monophosphates, leading to relaxation of smooth muscles of the corpora cavernosa and by this to tumescence and rigidity, i.e. erection. The diagnosis of neurologic causes of erectile dysfunction requires a detailed history and neurologic examination. Conventional neurophysiological procedures evaluate the function of rapidly conducting, thickly myelinated nerve fibers only. Therefore, techniques such as sphincter ani externus electromyography, latency measurements of the pudendal nerve or bulbocavernosus reflex studies frequently do not contribute to the diagnostic process. The evaluation of small nerve fibers that are essential for erection, for example by means of psychophysical quantitative thermotesting, might improve the diagnosis of neurogenic causes of erectile dysfunction. In addition, the assessment of heart rate variability at rest, during metronomic breathing, Valsalva maneuver, and active standing might be helpful to identify an autonomic neuropathy as the cause of erectile dysfunction.

Assessment and evaluation of hereditary sensory and autonomic neuropathies with autonomic and neurophysiological examinations.

The five different types of the rare hereditary sensory and autonomic neuropathies (HSAN) are classified by their mode of inheritance, pathology, natural history, biochemical, neurophysiologic and autonomic abnormalities. Clinically, the different types of HSANs can be identified by a detailed history and examination and 'bedside' tests of sympathetic or parasympathetic function such as active standing, metronomic breathing or the Valsalva maneuver, sensory and motor nerve conduction studies, quantitative sensory testing of thermal and vibratory perception, and the analysis of sudomotor function by recordings of the sympathetic skin response (SSR) or the sweat output during quantitative sudomotor axon reflex testing (QSART). The slowly progressive, symmetrical HSAN type I manifests between the second and fourth decade with ulcers or mutilations of the lower extremities, low normal sensory and motor nerve conduction velocities, but abnormal warm, cold and heat pain perception and distal anhidrosis. In HSAN type II, symptoms occur already in infancy, trophic alterations affect fingers and toes. There are acral anhidrosis and various autonomic dysfunctions such as tonic pupils, eating and swallowing difficulties, constipation, episodic fever, profound hypotonia and episodes of apnea. Sensory perception is severely impaired and accounts for elevated vibratory but also thermal perception thresholds. Sensory nerve conduction is highly abnormal while motor nerve conduction studies are almost normal. Type III, the autosomal recessive familial dysautonomia (FD), is the most common of the HSANs. FD is characterized by pronounced autonomic, primarily sympathetic dysregulation with severe orthostatic hypotension, repeated episodes of autonomic crises with excessive arterial hypertension, profuse sweating, skin blotching, puffy hands and behavioral abnormalities. FD manifests only in children of Ashkenazi Jewish ancestry. Cardinal findings are diminished deep tendon reflexes, absence of overflow tears, absence of fungi-form papillae of the tongue and of axon flare response following intradermal histamine injection. Thermal and vibratory testing show pronounced impairment of temperature and pain but also of vibratory perception. Children with HSAN IV, 'congenital insensitivity to pain with anhidrosis' experience repeated episodes of high fevers during high environmental temperature due to anhidrosis. The anhidrosis of the hyperkeratotic skin accounts for absence of the SSR or lack of sweat output during QSART. The patients' insensitivity to superficial as well as deep, visceral pain can be demonstrated e. g. by quantitative heat pain testing. Patients develop severe mutilations e. g. of the tip of their tongue, they might have severe burn injuries and multiple, unnoticed fractures with neuropathic joints. Children with the very rare HSAN type V respond normally to tactile, vibratory or thermal stimuli, but have a selective loss of pain perception with otherwise normal neurological examination. Painful stimuli reveal no signs of discomfort.

Heart rate variability measurement in diabetic neuropathy: review of methods.

Heart rate variability (HRV) is an important tool to analyze the autonomic function. It therefore has a special interest for early detection and ensuing treatment of autonomic neuropathy in diabetic patients. The aim of this work is to present a brief historical review of HRV, as well as a technical review of the most common methods to measure it. In this work is presented a system that performs three measurements of HRV. An overview of methodologies developed to quantify HRV is presented; this technical review covers the most common time and frequency domain techniques, for short and long periods of time, with comments about clinical utility of these tests. A system performing three standard tests of HRV, Anscore Health Management System, is presented. This system performs metronomic breathing (MT), the Valsalva Test (VT), and the Stand Test (ST). A normal range study with 212 healthy subjects in three centers (ages 20-80 years, with even age distribution, and even male and female distribution) was conducted. A subset of 45 subjects from the total number of subjects was selected for the reproducibility study, consisting of three measurements of each test. The normal range study showed a decrease in all the ratios with age and, for the Valsalva test, a difference among genders; 5th percentiles were calculated. The reproducibility study results, expressed as mean CV%, were 4.30% for the MT, 6.26% for the VT, and 6.66% for the ST. HRV is the most reliable measurement of autonomic function; when controlled maneuvers like MT, VT, and ST are performed, high reproducibility is obtained, with results comparable to that observed for nerve conduction studies. Such reproducibility makes autonomic function testing more feasible as a test component in multicenter studies of different neurological disorders.

Mechanisms of cerebral autoregulation, assessment and interpretation by means of transcranial doppler sonography

Cerebrovascular autoregulation assures constancy of cerebral perfusion despite blood pressure changes, as long as mean blood pressure remains in a range between 50-170 mmHg. Static and dynamic myogenic mechanisms dampen sudden blood pressure changes. Neurogenic influences of sympathetic, noradrenergic fibers modulate primarily proximal, large diameter segments of cerebral arteries, but also small 15-20 microns diameter vessels. Parasympathetic, vasodilating impulses are of less influence. Monoaminergic brainstem centers such as the dorsal raphe nucleus, locus coeruleus or nucleus reticularis pontis oralis also influence vessel tone. Metabolic, local parenchymal and endothelial substances have major impact on cerebral vessel tone. Particularly important are nitric oxide, calcitonin gene related peptide, substance P, endothelin, potassium channels and autocoids such as histamine, bradykinin, arachidonic acid, prostanoids, leucotrienes, free radicals or serotonin. The clinical examination of autoregulation is mostly based on brief blood pressure changes induced by drugs such as angiotensin, phenylephrine or sodium nitroprusside, or by challenge maneuvers. Frequently, blood pressure is challenged by a tilt-table maneuver, the "leg-cuff"-method according to Aaslid, or a Valsalva maneuver. The analysis of coherence and phase relation between spontaneous or metronomic breathing modulation of blood pressure and brain perfusion also assesses autoregulatory function. Cerebral blood flow is determined by means of transcranial Doppler sonography, mostly of the proximal segment of the mid-cerebral artery. There is some controversy whether a decrease of cerebral blood flow velocity measured at this segment indicates vasodilatation at the insonated segment or reflects blood flow reduction due to decreased perfusion of down-stream vessel segments. Various clinical and animal studies are presented demonstrating diameter constancy of the insonated mid-cerebral artery segment and thus indicating that slowing of mid cerebral artery blood flow velocity as assessed by transcranial Doppler sonography is due to a decrease of down-stream perfusion. Direct, intraoperative measurements of vessel diameter confirm this conclusion.

Exaggerated heart rate oscillations during two meditation techniques

We report extremely prominent heart rate oscillations associated with slow breathing during specific traditional forms of Chinese Chi and Kundalini Yoga meditation techniques in healthy young adults. We applied both spectral analysis and a novel analytic technique based on the Hilbert transform to quantify these heart rate dynamics. The amplitude of these oscillations during meditation was significantly greater than in the pre-meditation control state and also in three non-meditation control groups: i) elite athletes during sleep, ii) healthy young adults during metronomic breathing, and iii) healthy young adults during spontaneous nocturnal breathing. This finding, along with the marked variability of the beat-to-beat heart rate dynamics during such profound meditative states, challenges the notion of meditation as only an autonomically quiescent state.

Familial aggregation of heart rate variability based on short recordings - the kibbutzim family study

The objective of this study was to assess the familial aggregation of heart rate variability (HRV), a readily measurable noninvasive reflection of cardiac autonomic function. Familial correlations were analyzed in 451 kibbutz members aged 15-97 years belonging to 80 kindreds. Five-minute duration Holter recordings made during silent supine spontaneous breathing and metronomic breathing were analyzed in the time and frequency domains. The present analysis considers the familial correlations and the heritability estimates of two time-domain indices, the standard deviation (SD) of the R-R interval (RR), reflecting total variability, and the root mean square of successive differences in RR intervals (RMSSD), reflecting vagal (parasympathetic) tone. During free breathing, age- and sex-adjusted correlations between parents and their children (r=0.24 for both indices) and between adult siblings above 30 years of age (r=0.24 and t=0.34 for SD and RMSSD, respectively) were statistically significant, whereas spouse correlations (r=-0.04, r=-0.02 for SD and RMSSD, respectively) and correlations in younger siblings (r=-0.22 and r=0.01, respectively) were not. Significant heritability estimates were demonstrated for the two indices (h2=0.41 for SD and h2=0.39 for RMSSD). These findings suggest that familial aggregation of HRV characteristics is determined mostly by genetic factors and less so by environmental factors and provide a basis for continuing the investigation into the underlying genetic influences on HRV.

Voluntary control of breathing does not alter vagal modulation of heart rate

Variations in respiratory pattern influence the heart rate spectrum. It has been suggested, hence, that metronomic respiration should be used to correctly assess vagal modulation of heart rate by using spectral analysis. On the other hand, breathing to a metronome has been reported to increase heart rate spectral power in the high- or respiratory frequency region; this finding has led to the suggestion that metronomic respiration enhances vagal tone or alters vagal modulation of heart rate. To investigate whether metronomic breathing complicates the interpretation of heart rate spectra by altering vagal modulation, we recorded the electrocardiogram and respiration from eight volunteers during three breathing trials of 10 min each: 1) spontaneous breathing (mean rate of 14.4 breaths/min); 2) breathing to a metronome at the rate of 15, 18, and 21 breaths/min for 2, 6, and 2 min, respectively; and 3) breathing to a metronome at the rate of 18 breaths/min for 10 min. Data were also collected from eight volunteers who breathed spontaneously for 20 min and breathed metronomically at each subject's mean spontaneous breathing frequency for 20 min. Results from the three 10-min breathing trials showed that heart rate power in the respiratory frequency region was smaller during metronomic breathing than during spontaneous breathing. This decrease could be explained fully by the higher breathing frequencies used during trials 2 and 3 of metronomic breathing. When the subjects breathed metronomically at each subject's mean breathing frequency, the heart rate powers during metronomic breathing were similar to those during spontaneous breathing. Our results suggest that vagal modulation of heart rate is not altered and vagal tone is not enhanced during metronomic breathing.

Gender- and age-related differences in heart rate dynamics: Are women more complex than men?

Objectives. This study aimed to quantify the complex dynamics of beat-to-beat sinus rhythm heart rate fluctuations and to determine their differences as a function of gender and age.Background. Recently, measures of heart rate variability and the nonlinear “complexity” of heart rate dynamics have been used as indicators of cardiovascular health. Because women have lower cardiovascular risk and greater longevity than men, we postulated that there are important gender-related differences in beat-to-beat heart rate dynamics.Methods. We analyzed heart rate dynamics during 8-min segments of continuous electrocardiographic recording in healthy young (20 to 39 years old), middle-aged (40 to 64 years old) and elderly (65 to 90 years old) men (n = 40) and women (n = 27) while they performed spontaneous and metronomic (15 breaths/ min) breathing. Relatively high (0.15 to 0.40 Hz) and low (0.01 to 0.15 Hz) frequency components of heart rate variability were computed using spectral analysis. The overall “complexity” of each heart rate time series was quantified by its approximate entropy, a measure of regularity derived from nonlinear dynamics (“chaos” theory).Results. Mean heart rate did not differ between the age groups or genders. High frequency heart rate power and the high/low frequency power ratio decreased with age in both men and women (p < 0.05). The high/low frequency power ratio during spontaneous and metronomic breathing was greater in women than men (p < 0.05). Heart rate approximate entropy decreased with age and was higher in women than men (p < 0.05).Conclusions. High frequency heart rate spectral power (associated with parasympathetic activity) and the overall complexity of heart rate dynamics are higher in women than men. These complementary findings indicate the need to account for genderas well as age-related differences in heart rate dynamics. Whether these gender differences are related to lower cardiovascular disease risk and greater longevity in women requires further study.