Forfatterarkiv: Marius

Ukjent sin avatar

RR Interval Variability Is Inversely Related to Inflammatory Markers: The CARDIA Study

av

Bekrefter at svak vagus gir økt betennelse. Stor studie som inkluderte over 750 deltakere.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1892756/

Recent evidence reveals that the immune system is under the direct control of the vagus nerve via the “cholinergic anti-inflammatory pathway.” Stimulation of vagus nerve activity significantly inhibits cytokine levels in animal models, and cholinergic agents inhibit cytokine release by human macrophages. Moreover, when vagus nerve activity is decreased or absent, cytokines are overproduced. Atherosclerosis is an inflammatory disease characterized by elevated levels of CRP and IL-6, but the relationship between cardiac vagal activity and cytokine levels in healthy humans is not well understood. Here we measured RR interval variability, an index of cardiac vagal modulation, and CRP and IL-6 in 757 subjects participating in a subset of the year 15 data collection in the CARDIA study of the evolution of risk factors in young adults. Univariate analysis revealed that all indices of RRV were strongly and inversely related to IL-6 (log pg/mL b= −0.08 and −0.17 for HF and LF power, P < 0.001 respectively) and CRP (log mg/L b = −0.14 and −0.26 for HF and LF power, P < 0.001 respectively) levels. In the multivariate model including gender, race, age, smoking, physical activity, SBP, BMI, and disease, the inverse relationship between RRV and inflammatory markers, although slightly attenuated, remained significant. These findings are consistent with the hypothesis that diminished descending vagal anti-inflammatory signals can allow cytokine overproduction in humans.

To our knowledge, these are the first results demonstrating inverse relationships between inflammatory markers and indices of cardiac autonomic regulation in a large sample of healthy young adults. These findings are consistent with evidence from animal studies indicating that the cholinergic anti-inflammatory pathway counter-regulates inflammation.

It now appears that in our data from the CARDIA study of heart disease in young adults there is an inverse relationship between low frequency RR interval variability and the inflammatory markers IL-6 and CRP, even after control of relevant covariates and cardioactive medications or hypertension or diabetes, which is consistent with the hypothesis of a cholinergic anti-inflammatory pathway that regulates inflammation in humans.

Ukjent sin avatar

Behavioural modification of the cholinergic anti-inflammatory response to C-reactive protein in patients with hypertension

av

Denne beskriver hvordan regulering av pusten kan påvirke vagus nerven til å dempe betennelser og redusere CRP (en betennelsesmarkør) i blodet.

http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2796.2012.02523.x/full

Objectives.  A central hypothesis of the cholinergic anti-inflammatory reflex model is that innate immune activity is inhibited by the efferent vagus. We evaluated whether changes in markers of tonic or reflex vagal heart rate modulation following behavioural intervention were associated inversely with changes in high-sensitivity C-reactive protein (hsCRP) or interleukin-6 (IL-6).

Design.  Subjects diagnosed with hypertension (n = 45, age 35–64 years, 53% women) were randomized to an 8-week protocol of behavioural neurocardiac training (with heart rate variability biofeedback) or autogenic relaxation. Assessments before and after intervention included pro-inflammatory factors (hsCRP, IL-6), markers of vagal heart rate modulation [RR high-frequency (HF) power within 0.15–0.40 Hz, baroreflex sensitivity and RR interval], conventional measures of lipoprotein cholesterol and 24-h ambulatory systolic and diastolic blood pressure.

Results.  Changes in hsCRP and IL-6 were not associated with changes in lipoprotein cholesterol or blood pressure. After adjusting for anti-inflammatory drugs and confounding factors, changes in hsCRP related inversely to changes in HF power (β =−0.25±0.1, P = 0.02), baroreflex sensitivity (β = −0.33±0.7, P = 0.04) and RR interval (β = −0.001 ± 0.0004, P = 0.02). Statistically significant relationships were not observed for IL-6.

Conclusions.  Changes in hsCRP were consistent with the inhibitory effect of increased vagal efferent activity on pro-inflammatory factors predicted by the cholinergic anti-inflammatory reflex model. Clinical trials for patients with cardiovascular dysfunction are warranted to assess whether behavioural interventions can contribute independently to the chronic regulation of inflammatory activity and to improved clinical outcomes.

Chronic low-grade inflammation contributes to the development of experimental and clinical hypertension [1–3], and it increases the risk for myocardial infarction, stroke and sudden cardiac death [4]. C-reactive protein (CRP) is an established index of systemic inflammation. It is produced chiefly by hepatocytes under the regulation of a cascade of pro-inflammatory cytokines [tumour necrosis factor-α (TNF-α), interleukin-1ß [IL-1ß] and IL-6] that are expressed in response to conditions that include vascular injury and infection. In addition, CRP is produced by human coronary artery smooth muscle cells following exposure to pro-inflammatory cytokines [5], which suggests that it may contribute independently to endothelial dysfunction and atherogenesis [6].

Clinical trials that have attempted to modify vagal efferent activity by means of aerobic exercise [17, 18], resistance exercise [19] or device-guided vagal nerve stimulation [20–22] have yet to demonstrate consequent reduction in pro-inflammatory activity that is independent of confounding factors such as anti-inflammatory medications.

Subjects received four weekly and two biweekly 1-h sessions of behavioural neurocardiac training or autogenic relaxation, as described previously [23]. Home practice sessions complemented the laboratory-based training. All sessions began with a 10-min review of cognitive-behavioural guidelines for managing daily stress [25].

At the completion of each task, subjects were trained to cognitively disengage from negative or aroused affect and to focus attention on slowing respiration (within their comfort zone) to 10-s cycles (6 breaths min−1). During each countering exercise, subjects were guided by the use of biofeedback to increase RR spectral power at approximately 0.1 Hz, as shown on a biofeedback display of the RR power spectrum (0.003–0.5 Hz) and breaths min−1.

The major finding of this study is that following an 8-week protocol of behavioural neurocardiac training or autogenic relaxation amongst patients with hypertension, change in hsCRP was associated independently and inversely with changes in tonic and reflex vagal heart rate modulation as measured by RR high-frequency power (ms2 per Hz), baroreflex sensitivity (ms per mmHg) and lengthening of the RR interval (ms). A statistical trend in the data suggested a similar inverse association between changes in IL-6 and RR high-frequency power.

A central hypothesis of the cholinergic anti-inflammatory reflex model is that the innate immune response is regulated, in part, by rapid and localized efferent activity of the vagus nerve. Previous reviews have identified the functional anatomy and neural mechanisms of this model [10, 29, 30]. In brief, efferent fibres of the vagus nerve comprise a neural anti-inflammatory pathway that culminates in the release of acetylcholine in proximate sites where pro-inflammatory factors have been expressed. Acetylcholine has been shown to bind to subunit α7 of nicotinic acetylcholine receptors on cytokine-producing immune cells [30]. This inhibits the activation of NF-κB and the subsequent expression of a pro-inflammatory cascade that includes TNF-α, IL-6 and CRP [10].

To our knowledge, the present proof of principle study involving hypertensive patients provides the most direct evaluation of whether augmentation of tonic or reflex vagal heart rate modulation, in this instance by a behavioural intervention, attenuates independently pro-inflammatory activity as assessed by hsCRP and IL-6. It is noteworthy that the present findings were observed following only modest changes in markers of vagal HR modulation. Previous behavioural trials of heart rate variability biofeedback or relaxation [32–34] have reported a small but statistically significant increase in vagal HR modulation. Similarly, behavioural training is associated with a modest, but statistically significant decrease in proinflammatory factors, including hsCRP and IL-6 [35], although heart rate variability biofeedback failed to reduce other inflammatory factors following experimental administration of an endotoxin (lipopolysaccharide) [36].

In sum, the present findings support the model of a cholinergic anti-inflammatory reflex when pro-inflammatory activity is measured by hsCRP. Clinical trial evidence has demonstrated that behavioural interventions can significantly augment vagal heart rate modulation or cardiovagal baroreflex gain through the use of relaxation training and biofeedback [32–34].

Ukjent sin avatar

Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve

av

Viser hvordan tarmbakterier påvirker vagusnerven. Mus som har fått vagusnerven fjernet opplevde ingen av de stress-,  angst,  og depresjonsreduserende effektene av Lactobacillus Rhamnosus tilskudd. Dette viser hvor viktig vagusnerven er i kommunikasjonen mellom hjerne og tarmsystem.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3179073/

ABSTRACT

There is increasing, but largely indirect, evidence pointing to an effect of commensal gut microbiota on the central nervous system (CNS). However, it is unknown whether lactic acid bacteria such as Lactobacillus rhamnosus could have a direct effect on neurotransmitter receptors in the CNS in normal, healthy animals. GABA is the main CNS inhibitory neurotransmitter and is significantly involved in regulating many physiological and psychological processes. Alterations in central GABA receptor expression are implicated in the pathogenesis of anxiety and depression, which are highly comorbid with functional bowel disorders. In this work, we show that chronic treatment with L. rhamnosus (JB-1) induced region-dependent alterations in GABAB1b mRNA in the brain with increases in cortical regions (cingulate and prelimbic) and concomitant reductions in expression in the hippocampus, amygdala, and locus coeruleus, in comparison with control-fed mice. In addition, L. rhamnosus(JB-1) reduced GABAAα2 mRNA expression in the prefrontal cortex and amygdala, but increased GABAAα2 in the hippocampus. Importantly, L. rhamnosus (JB-1) reduced stress-induced corticosterone and anxiety- and depression-related behavior. Moreover, the neurochemical and behavioral effects were not found in vagotomized mice, identifying the vagus as a major modulatory constitutive communication pathway between the bacteria exposed to the gut and the brain. Together, these findings highlight the important role of bacteria in the bidirectional communication of the gut–brain axis and suggest that certain organisms may prove to be useful therapeutic adjuncts in stress-related disorders such as anxiety and depression.

There is increasing evidence suggesting an interaction between the intestinal microbiota, the gut, and the central nervous system (CNS) in what is recognized as the microbiome–gut–brain axis (1–4). Studies in rodents have implicated dysregulation of this axis in functional bowel disorders, including irritable bowel syndrome. Indeed, visceral perception in rodents can be affected by alterations in gut microbiota (5). Moreover, it has been shown that the absence and/or modification of the gut microflora in mice affects the hypothalamic–pituitary–adrenal (HPA) axis response to stress (6, 7) and anxiety behavior (8, 9), which is important given the high comorbidity between functional gastrointestinal disorders and stress-related psychiatric disorders, such as anxiety and depression (10). In addition, pathogenic bacteria in rodents can induce anxiety-like behaviors, which are mediated via vagal afferents (9, 11).

Accumulating clinical evidence suggests that probiotics can modulate the stress response and improve mood and anxiety symptoms in patients with chronic fatigue and irritable bowel syndrome (15, 16). One such organism isLactobacillus rhamnosus (JB-1), which has been demonstrated to modulate the immune system because it prevents the induction of IL-8 by TNF-α in human colon epithelial cell lines (T84 and HT-29) (17) and modulates inflammation through the generation of regulatory T cells (18). Moreover, it inhibits the cardio–autonomic response to colorectal distension (CRD) in rats (19), reduces CRD-induced dorsal root ganglia excitability (20), and affects small intestine motility (21).

Stress-induced levels of corticosterone are significantly lower in L. rhamnosus(JB-1)-fed mice compared with broth fed control animals (###P < 0.001).

Furthermore, in this study we observed that L. rhamnosus (JB-1) administration reduces the stress-induced elevation in corticosterone, suggesting that the impact of the Lactobacillus on the CNS has an important effect at a physiological level. Alterations in the HPA axis have been linked to the development of mood disorders and have been shown to affect the composition of the microbiota in rodents (26). Our data are in line with previous studies showing that subchronic or chronic treatment with antidepressants can prevent forced swim stress-induced increases in plasma corticosterone in both mice and rats (27). Moreover, it has been shown that alterations in HPA axis modulation can be reversed by treatment with Lactobacillus andBifidobacterium (28, 29).

The vagus nerve plays a major role in communicating changes in the gastrointestinal tract to the CNS (3). In the present study, Vx prevented the anxiolytic and antidepressant effects of L. rhamnosus (JB-1) and also the changes in GABAAα2 and GABAAα1 mRNAs in the amygdala (SI Materials and Methods), as well as GABAAα1mRNA in the hippocampus.

Moreover, vagus nerve stimulation has been described as a successful approach to treat some (44), but not all (45), patients with treatment-resistant depression, which further suggests the importance of the vagus nerve in the modulation of behavior.

 Nonetheless, our data conclusively demonstrate that a potential probiotic can robustly alter brain neurochemistry and behavior relevant to anxiety- and depression-related behavior in mice.

Ukjent sin avatar

Heartbeat Synchronizes With Respiratory Rhythm Only Under Specific Circumstances

av

Dette er et svar på en studie hvor de viser at HRV er høyest ved 0.1 Hz (6 pust/min).

http://journal.publications.chestnet.org/article.aspx?articleid=1082860

we determined that the phase relationship between heart rate and respiration was 0° only at a respiratory frequency of approximately 0.1 Hz, in which the target frequency heart rate variability also was highest (Fig 1 ).

Ukjent sin avatar

Kritikk til polyvagal teorien og mye viktig om vagus-pust forbindelsen

av

Svært viktig studie som forteller om alle aspekter ved vagus nervens og pustens relasjon. Nevner at det ikke er en direkte relasjon, og at det blir ikke riktig å si at RSA/HRV er en direkte intdikasjon på vagus nervens funksjon. Mange faktorer spiller inn. Sier også at vagus fyrer av like mye, men når pustefrekvensen synker blir signalene sterkere i løpet av den lange utpusten. Nevner også at i individet er det tydelig sammenheng mellom pust og HRV, men mellom forskjellige individer er det store forskjeller. Nevner også at vagus nerven fyrer av når CO2 øker for øke gassutvekslingen mellom blod og luft.

http://www.ncbi.nlm.nih.gov/pubmed/17081672

Mer fra studien er her.

Abstract

Respiratory sinus arrhythmia (RSA, or high-frequency heart-rate variability) is frequently employed as an index of cardiac vagal tone or even believed to be a direct measure of vagal tone. However, there are many significant caveats regarding vagal tone interpretation:

1. Respiratory parameters can confound relations between RSA and cardiac vagal tone.

2. Although intraindividual relations between RSA and cardiac vagal control are often strong, interindividual associations may be modest.

3. RSA measurement is profoundly influenced by concurrent levels of momentary physical activity, which can bias estimation of individual differences in vagal tone.

4. RSA magnitude is affected by beta-adrenergic tone.

5. RSA and cardiac vagal tone can dissociate under certain circumstances.

6. The polyvagal theory contains evolution-based speculations that relate RSA, vagal tone and behavioral phenomena.

We present evidence that the polyvagal theory does not accurately depict evolution of vagal control of heart-rate variability, and that it ignores the phenomenon of cardiac aliasing and disregards the evolution of a functional role for vagal control of the heart, from cardiorespiratory synchrony in fish to RSA in mammals. Unawareness of these issues can lead to misinterpretation of cardiovascular autonomic mechanisms. On the other hand, RSA has been shown to often provide a reasonable reflection of cardiac vagal tone when the above-mentioned complexities are considered. Finally, a recent hypothesis is expanded upon, in which RSA plays a primary role in regulation of energy exchange by means of synchronizing respiratory and cardiovascular processes during metabolic and behavioral change.

Ukjent sin avatar

Evoked Pain Analgesia in Chronic Pelvic Pain Patients using Respiratory-gated Auricular Vagal Afferent Nerve Stimulation

av

I medisinsk sammenheng benyttes ofte elektrisk stimuli i øret for å styrke vagusnerven gjennom dens forbindelse til huden i øret. I denne studien viser de at vagus nerven stimuleres best om man synkroniserer stimulien med utpust. Denne kobler altså medisinsk stimuli med pustens stimuli. Men de har ingen oppmerksomhet på mulighetene ved å senke pustefrekvens samtidig.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3376238/

Chronic pain disorders such as CPP are in great need of effective, non-pharmacological options for treatment. RAVANS (Respiratory-gated Auricular Vagal Afferent Nerve Stimulation) produced promising anti-nociceptive effects for QST outcomes reflective of the noted hyperalgesia and central sensitization in this patient population. Future studies should evaluate longer-term application of RAVANS to examine its effects on both QST outcomes and clinical pain.

The analgesic mechanisms of VNS have not been fully elucidated, but are likely mediated by afferent (not efferent) input to supraspinal brain regions [16]. Vagal afference is relayed to the nucleus tractus solitarious (NTS) in the medullary brainstem. Importantly, the NTS also receives somatosensory afference via the auricular branch of the vagus (ABV) nerve from specific portions of the auricle [17]. ABV afference is transmitted to both the NTS [17] and the spinal trigeminal nucleus (SpV) [18], by neurons located in the superior (jugular) ganglion of the vagus nerve. Respiration can modulate NTS activity directly (the lungs are innervated by the vagus nerve) and indirectly. In regard to the latter, inspiration increases venous return to the thorax, which increases arterial pressure, and hence vagal (and glossopharyngeal n.) afference to the NTS via aortic and carotid baroreceptors, respectively [19]. The NTS then inhibits efferent vagal outflow to the heart [20, 21], leading to a transient inspiratory tachycardia with every breath. This feedback loop is termed “respiratory sinus arrhythmia” [22]. Hence, the dorsal medullary vagal system operates in tune with respiration, and we propose that supplying vagal afferent stimulation gated to the exhalation phase of respiration (i.e. when thoracic baroreceptor afference does not enter the NTS), will optimize t-VNS therapy (see Figure 1 for schematic). Furthermore, such intermittent, irregular stimulation (i.e., varying with respiration) will also mitigate classical neuronal adaptation/accomodation, which can occur with continuous stimulation of NTS neurons [23].

 

Ukjent sin avatar

Autonomic system modification in zen practitioners

av

Nevner mye om hvordan pustefrekvens påvirker HRV og  andre faktorer. Og spesielt hvordan dette endrer den normale pusten på lang sikt.

http://www.ncbi.nlm.nih.gov/pubmed/24469560

http://www.indianjmedsci.org/article.asp?issn=0019-5359;year=2013;volume=67;issue=7;spage=161;epage=167;aulast=Fiorentini

Background: Meditation in its various forms is a traditional exercise with a potential benefit on well-being and health. On a psychosomatic level these exercises seem to improve the salutogenetic potential in man.Especially the cardiorespiratory interaction seems to play an important role since most meditation techniques make use of special low frequency breathing patterns regardless of whether they result from a deliberate guidance of breathing or other mechanisms, for example, the recitation of specific verse. During the different exercises of Zen meditation the depth and the duration of each respiratory cycle is determined only by the process of breathing. Respiratory manoeuvres during Zazen meditation may produce HR variability changes similar to those produces during biofeedback.Recognition that the respiratory sinus arrhythmia (RSA) was mediated by efferent vagal activity acting on the sinus node led investigators to attempt to quantify the fluctuations in R-R intervals that were related to breathing. Materials and Methods: Nine Zen practitioners with five years of experience took part in the study. Autonomic nervous system function was evaluated by heart rate variability (HRV) analysis during 24-hours ECG recording during zen meditation and at rest. Results: The data of this small observational study confirm that ZaZen breathing falls within the range of low frequency HR spectral bands. Our data suggest that the modification of HR spectral power remained also in normal day when the subject have a normal breathing. Conclusion: We suggest that the changes in the breathing rate might modify the chemoreflex and the continuous practice in slow breathing can reduce chemoreflex. This change in the automonic control of respiration can be permanent with a resetting of endogenous circulatory rhythms.

Figure 1: Power spectrum analysis of heart rate variability during zen meditation

Figure 2: Power spectrum analysis of heart rate variability to rest

In conclusion, repeated training to slow down breathing reduces the spontaneous breathing rate with long term effects on the cardiovascular control mechanisms. Indeed, when respiration slows to about 6 cycles/min, as in Zen practitioners and in the frequency range of the spontaneous LF oscillation, the cardiovascular fluctuations become maximal. The changes in the breathing rate might modify the chemoreflex and the continuous practice in slow breathing can reduce chemoreflex. This change in the autonomic control of respiration can be permanent with a resetting of endogenous circulatory rhythms.

Ukjent sin avatar

Relationship between dysfunctional breathing patterns and ability to achieve target heart rate variability with features of «coherence» during biofeedback.

av

Nevner hvordan en topp-pust relateres til lav HRV og problemer i hjerte/kar systemet.

http://www.ncbi.nlm.nih.gov/pubmed/22164811

Abstract

BACKGROUND:

Heart rate variability (HRV) biofeedback is a self-regulation strategy used to improve conditions including asthma, stress, hypertension, and chronic obstructive pulmonary disease. Respiratory muscle function affects hemodynamic influences on respiratory sinus arrhythmia (RSA), and HRV and HRV-biofeedback protocols often include slow abdominal breathing to achieve physiologically optimal patterns of HRV with power spectral distribution concentrated around the 0.1-Hz frequency and large amplitude. It is likely that optimal balanced breathing patterns and ability to entrain heart rhythms to breathing reflect physiological efficiency and resilience and that individuals with dysfunctional breathing patterns may have difficulty voluntarily modulating HRV and RSA. The relationship between breathing movement patterns and HRV, however, has not been investigated. This study examines how individuals’ habitual breathing patterns correspond with their ability to optimize HRV and RSA.

METHOD:

Breathing pattern was assessed using the Manual Assessment of Respiratory Motion (MARM) and the Hi Lo manual palpation techniques in 83 people with possible dysfunctional breathing before they attempted HRV biofeedback. Mean respiratory rate was also assessed. Subsequently, participants applied a brief 5-minute biofeedback protocol, involving breathing and positive emotional focus, to achieve HRV patterns proposed to reflect physiological «coherence» and entrainment of heart rhythm oscillations to other oscillating body systems.

RESULTS:

Thoracic-dominant breathing was associated with decreased coherence of HRV (r = -.463, P = .0001). Individuals with paradoxical breathing had the lowest HRV coherence (t(8) = 10.7, P = .001), and the negative relationship between coherence of HRV and extent of thoracic breathing was strongest in this group (r = -.768, P = .03).

CONCLUSION:

Dysfunctional breathing patterns are associated with decreased ability to achieve HRV patterns that reflect cardiorespiratory efficiency and autonomic nervous system balance. This suggests that dysfunctional breathing patterns are not only biomechanically inefficient but also reflect decreased physiological resilience. Breathing assessment using simple manual techniques such as the MARM and Hi Lo may be useful in HRV biofeedback to identify if poor responders require more emphasis on correction of dysfunctional breathing.

Ukjent sin avatar

Trigger point dry needling as an adjunct treatment for a patient with adhesive capsulitis of the shoulder.

av

Nevner gode resultater på forzen shoulder med nålebehandlng av skuldermuskulatur. Men det er bare beskrivelse av en enkelt case, med 13 behandlinger på 6 uker.

http://www.ncbi.nlm.nih.gov/pubmed/24261931

Abstract

STUDY DESIGN:

Case report.

BACKGROUND:

Prognosis for adhesive capsulitis has been described as self-limiting and can persist for 1 to 3 years. Conservative treatment that includes physical therapy is commonly advised.

CASE DESCRIPTION:

The patient was a 54-year-old woman with primary symptoms of shoulder pain and loss of motion consistent with adhesive capsulitis. Manual physical therapy intervention initially consisted of joint mobilizations of the shoulder region and thrust manipulation of the cervicothoracic region. Although manual techniques seemed to result in some early functional improvement, continued progression was limited by pain. Subsequent examination identified trigger points in the upper trapezius, levator scapula, deltoid, and infraspinatus muscles, which were treated with dry needling to decrease pain and allow for higher grades of manual intervention.

OUTCOMES:

The patient was treated for a total of 13 visits over a 6-week period. After trigger point dry needling was introduced on the third visit, improvements in pain-free shoulder range of motion and functional outcome measures, assessed with the Shoulder Pain and Disability Index and the shortened form of the Disabilities of the Arm, Shoulder and Hand questionnaire, exceeded the minimal clinically important difference after 2 treatment sessions. At discharge, the patient had achieved significant improvements in shoulder range of motion in all planes, and outcome measures were significantly improved.

DISCUSSION:

This case report describes the clinical reasoning behind the use of trigger point dry needling in the treatment of a patient with adhesive capsulitis. The rapid improvement seen in this patient following the initiation of dry needling to the upper trapezius, levator scapula, deltoid, and infraspinatus muscles suggests that surrounding muscles may be a significant source of pain in this condition.