Heart rate variability biofeedback: how and why does it work?

Bekrefter alle elementer jeg jobber med i Autonom pust: vagus, betennelse, m.m.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4104929/

In recent years there has been substantial support for heart rate variability biofeedback (HRVB) as a treatment for a variety of disorders and for performance enhancement (Gevirtz, 2013). Since conditions as widely varied as asthma and depression seem to respond to this form of cardiorespiratory feedback training, the issue of possible mechanisms becomes more salient. The most supported possible mechanism is the strengthening of homeostasis in the baroreceptor (Vaschillo et al., 2002Lehrer et al., 2003). Recently, the effect on the vagal afferent pathway to the frontal cortical areas has been proposed. In this article, we review these and other possible mechanisms that might explain the positive effects of HRVB.

ANTI-INFLAMMATORY EFFECTS

It is known that the vagal system interacts closely with the inflammatory system, such that increases in vagus nerve traffic (usually produced by electrical vagal stimulation) are associated with decreases in serum levels of various inflammatory cytokines (Borovikova et al., 2000Tracey, 2002). One study did find a decrease in C-reactive proteins among hypertensive patients treated with HRV biofeedback (Nolan et al., 2012). In another study, we experimentally exposed healthy subjects to an inflammatory cytokine, lipopolysaccharide (Lehrer et al., 2010). Usually both sympathetic and parasympathetic activity is blocked by lipopolysaccharide. Although no biofeedback-induced decreases in inflammatory cytokines were found, the autonomic effects of inflammation were greatly modulated, indicating that a greater resiliency was preserved among individuals given HRV biofeedback.

Matoverfølsomhet – et paradigmeskifte

Artikkel skrevet i 2011 som nevner mange viktige poenger. Blandt annet at vagus svekkes ved IBS og at det gir andre plager, spesielt hudplager.

http://www.naaf.no/Documents/Allergi%20i%20Praksis/matoverfoelsomhet_aip_1_2011w_v2.pdf

Dessuten hadde mange pasienter ekstra-intesti- nale symptomer og skåret høyt på «Subjective Health Complaints» (1). Påfallende mange anga at de hadde kronisk tretthet samt leddsmerter med morgenstivhet uten påvisbar artritt. Livskvaliteten var til dels be- tydelig redusert (2).

Over 50% av pasientene tilfreds- stilte kravene til en psykiatrisk diag- nose. Men hvor mye av de psykologiske problemene kan være sekundære? Inntil for knapt 20 år siden ble også magesårsykdommen regnet som en psykosomatisk sykdom. De psykolo- giske problemene vi så hos ulcuspasi- entene var ganske like de vi nå finner hos de matoverfølsomme, og vi har enda friskt i minnet hvordan alle pro- blemene hos ulcuspasientene, in- kludert de psykologiske, «blåste bort» etter fjerning av magesårbakterien Helicobacter pylori (4).

Kun sykdomspesifikk angst eller for- ventninger om plager var signifikante uavhengige prediktorer. Disse pre- diktorene forklarte dog til sammen ikke mer enn 10% av variansen i mageplagene, og alder var eneste signifikante prediktor av ekstra- intestinale plager. Det vil si at 90% av variansen i grad av somatiske plager ikke kunne forklares av psyko- logiske faktorer. Vi tror derfor nå at mange av de psykologiske problemene ved matoverfølsomhet er sekundære og at betydningen av psykologiske faktorer som årsak til matoverfølsomhet kan være betydelig overdrevet.

Vi kunne vise at et tungt fordøyelig, men fermenter- bart karbohydrat, som laktulose, ofte reproduserte pasientens plager (6). tester på klassisk IgE-sensitivisering mot spesifikke kostproteiner, deri- mot, var sjeldent positive. Det virker som om mageplagene først og fremst trigges av tungt fordøyelige karbo- hydrater og ikke spesielt av proteiner i kosten. Dessuten, at plagene kunne reproduseres av mat, viser at pasien- ten har rett – plagene kan skyldes maten! Det passer med at pasientene ikke har plager om natta, når de faster, etter tarm- skylling eller når de får tømt seg fullstendig.

Over 60% av pasientene hadde indikasjon på atopisk sykdom (Dette er hud- og slimhinnerelaterte sykdommer som allergi, tørr hud, kløe, m.m.)

Histamin øker sympatisk og redusert para- sympatisk (vagal) tonus, som også er karakteristisk for pasienter med funksjonelle mageplager (16, 17). Slik endret autonom aktivitet kan være et resultat av IgE-mediert histaminfrigjøring fra lokalt sensibili- serte mastceller (18).

Systemiske symptomer som kro- nisk tretthet og leddsmerter hos pasi- enter med IBS har tidligere ofte blitt forklart som somatisering av psykolo- giske problemer, men det finnes andre muligheter. For eksempel er det nylig rapportert at symptomer ved kronisk tretthetssyndrom kan behandles med en B-celle-antagonist (rituximab) (21). I likhet med de matoverfølsomme, har pasienter med kronisk tretthets- syndrom ofte IBS og endret mikro- flora som kan være av betydning for immunaktiveringen hos disse pasi- entene (22). Hos matoverfølsomme med IBS har vi nylig påvist økt nivå av B-celle aktiverende faktor (BAFF) i blod og tarmskyllevæske (23). BAFF er relatert til autoimmunitet og lokal immunaktivering i tarmen («lokal allergi») (24).

At karbohydrater kan reprodusere mageplagene hos pasienter med IBS og matoverfølsomhet, er verdt å merke seg, og mye tyder på at dette allerede nå bør få terapeutiske konsekvenser (27). Vi ser med andre ord for oss et paradigmeskifte når det gjelder utredning og behandling av pasienter med IBS og matoverfølsomhet.

RR interval-respiratory signal waveform modeling in human slow paced and spontaneous breathing.

Enda en bekreftelse på at pusten påvirker vagusnerven, og vagusnerven påvirker betennelser. Og at 0,1Hz (6 pust i minuttet) gir sterkest påvirkning på vagusnerven.

http://www.ncbi.nlm.nih.gov/pubmed/25139803/

Denne studien var en datamodell av hvordan forskjellige elementer av pusten (dybde og hastighet i dette tilfellet) påvirker hjerterytmen, som uttrykker vagusnerven. De fant at pustefrekvensen påvirket mest, altså hastigheten i dette tilfellet. 

The model’s results depended on breathing frequency with the least error occurring during slow paced breathing.

Deres forklaring på hvorfor pusten påvirker hjerterytmen er at strekk-reseptorer i lungene sier ifra om lungevolum som hjernen så bruker til å vurdere kardiovagale (vagusnervens påvirkning på hjertet) signaler.

Assuming that a0 represents slowly adapting pulmonary stretch receptors (SARs) and a1 SARs in coordination with other stretch receptors and central integrative coupling; then pulmonary stretch receptors relaying the instantaneous lung volume are the major factor determining cardiovagal output during inspiration.

De sier at ved forskjellige sykdommer blir det dårligere forbindelse mellom blodstrømning, blodtrykk, hjerterytme og pust, som gir ustabil kardivagal styring.

The role of vagal afferent neurons in cardiorespiratory coupling may relate to neurocardiovascular diseases in which weakened coupling among venous return, arterial pressure, heart rate and respiration produces cardiovagal instability.

Dette kan bidra til saktere, eller manglende, helbredelse av sykdom. Når man lærer å bruke pusten til å styrke vagusnerven er man i det minste én faktor nærmere helbredelse.

 

Systemic inflammation impairs respiratory chemoreflexes and plasticity

Denne studien beskriver hvordan systemisk betennelse påvirker pustefunksjonen og gjør at det blir vanskeligere å endre pustemønser, f.eks. å gjøre pusteøvelser, eller å tilpasse pusten til aktivitetsnivå. Spesielt den kjemiske og motoriske delen av pustefysiologien blir dårligere. Noe som viser seg i laver CO2 sensitivitet (kjemisk) og svakere pustemuskler (Motorisk).

Nevner spesielt at det er mikroglia celler i CNS som påvirkes av betennelse, og som kan oppretthodle betennelse siden de sender ut cytokiner, m.m. Astrosytter kan også bidra mye siden de aktiverer NFkB. Den gode nyheten her er at økt CO2 nedregulerer NFkB. TLR-4 (Toll-like receptor) aktiveres av patogener og problemer i cellene, og aktiverer NFkB, og nedreguleres av økt CO2.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3172820/

Abstract

Many lung and central nervous system disorders require robust and appropriate physiological responses to assure adequate breathing. Factors undermining the efficacy of ventilatory control will diminish the ability to compensate for pathology, threatening life itself. Although most of these same disorders are associated with systemic and/or neuroinflammation, and inflammation affects neural function, we are only beginning to understand interactions between inflammation and any aspect of ventilatory control (e.g. sensory receptors, rhythm generation, chemoreflexes, plasticity). Here we review available evidence, and present limited new data suggesting that systemic (or neural) inflammation impairs two key elements of ventilatory control: chemoreflexes and respiratory motor (vs. sensory) plasticity. Achieving an understanding of mechanisms whereby inflammation undermines ventilatory control is fundamental since inflammation may diminish the capacity for natural, compensatory responses during pathological states, and the ability to harness respiratory plasticity as a therapeutic strategy in the treatment of devastating breathing disorders, such as during cervical spinal injury or motor neuron disease.

Most lung and CNS disorders are associated with systemic and/or neural inflammation, including chronic lung diseases (Stockley, 2009), traumatic, ischemic and degenerative neural disorders (Teeling and Perry, 2009) and obstructive sleep apnea.

Systemic inflammation affects sensory receptors that modulate breathing, but can also trigger inflammatory responses in the central nervous system (CNS) through complex mechanisms. The primary CNS cells affected during systemic inflammation are microglia, the resident immune cells of the CNS, and astrocytes (Lehnardt, 2010).

Even when in their “resting state,” microglia are highly active, surveying their environment (Raivich, 2005,Parkhurst and Gan, 2010). When confronted with pathological conditions, such as neuronal injury/degeneration or bacterial/viral/fungal infection, they become “activated,” shifting from a stellate, ramified phenotype to an amoeboid shape (Kreutzberg, 1996). Activated microglia can be phagocytic, or they can release toxic and protective factors, including cytokines, prostaglandins, nitric oxide or neurotrophic factors (e.g. BDNF) (Kreutzberg, 1996Graeber, 2010). Despite the importance of microglia in immune function, they are diffuse in the CNS (~70-90% of CNS cells are glia; microglia are ~5-10% of those cells).

Astrocytes, on the other hand, contribute to the overall inflammatory response since they release cytokines, triggering nuclear factor-kappa B (NFκB) signaling elsewhere in the CNS. Further, they express many TLRs, including TLR-4, capable of eliciting an inflammatory response (Li and Stark, 2002Farina et al., 2007,Johann et al., 2008). Given their relative abundance, astrocytes may play a key role in CNS inflammatory responses.

TLR-4 receptors are cytokine family receptors that activate transcription factors, such as NFκB (Lu et al., 2008). NFκB regulates the expression of many inflammatory genes, including: IL-1β, -6 and -18, TNFα, cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) (Ricciardolo et al., 2004Nam, 2006). Endogenous molecules known to activate TLR-4 receptors include (but are not limited to) heat shock proteins (specifically HSP60, Ohashi et al., 2000Lehnardt et al., 2008), fibrinogen, surfactant protein-A, fibronectin extra domain A, heparin sulfate, soluble hyaluronan, β-defensin 2 and HMGB1 (Chen et al., 2007).

The role of inflammation (and specifically microglia) in chronic pain has been studied extensively (reviewed in Woolf and Salter, 2000Trang et al., 2006Mika, 2008Abbadie et al., 2009Baumbauer et al., 2009). A remarkable story has emerged, demonstrating the interplay between neurons, microglia, inflammation and plasticity in this spinal sensory system. In short, inflammation induces both peripheral and central sensitization, leading to allodynia (hypersensitivity to otherwise non-painful stimuli) and hyperalgesia (exaggerated or prolonged responses to a noxious stimulus) (Mika, 2008).

An important aspect of ventilatory control susceptible to inflammatory modulation is the chemoreflex control of breathing. Chemoreflexes are critical for maintaining homeostasis of arterial blood gases viaclassical negative feedback (Mitchell et al., 2009), or acting as “teachers” that induce plasticity in the respiratory control system (Mitchell and Johnson, 2003). Major chemoreflexes include the hypoxic (Powell et al., 1998) and hypercapnic ventilatory responses (Nattie, 2001), arising predominantly from the peripheral arterial and central chemoreceptors (Lahiri and Forster, 2003).

To date, no studies have reported the impact of systemic inflammation on hypercapnic responses. However, increased CO2 suppresses NFκB activation, possibly suppressing inflammatory gene expression (Taylor and Cummins, 2011). In fact, hypercapnia has been used to treat ischemia/reperfusion injury to decrease inflammation and reduce lung tissue damage (Laffey et al., 2000O’Croinin et al., 2005Curley et al., 2010Li et al., 2010).

Further work concerning the influence of systemic inflammation on hypercapnic ventilatory responses is warranted, particularly since impaired CO2 chemoreflexes would allow greater hypercapnia and minimize the ongoing inflammation; in this sense, impaired hypercapnic ventilatory responses during inflammation may (in part) be adaptive.

Heart rate variability, overnight urinary norepinephrine and C-reactive protein: evidence for the cholinergic anti-inflammatory pathway in healthy human adults.

Stor studie med 611 friske arbeidere som viser at lav HRV assosieres med betennelser (CRP).

http://www.ncbi.nlm.nih.gov/pubmed/19019182

Abstract

OBJECTIVES:

C-reactive protein (CRP) has been identified as an independent predictor of cardiovascular mortality and morbidity in population-based studies. Recent advances have suggested a prominent role for the autonomic nervous system (ANS) in the regulation of inflammation. However, no in vivo human studies have examined indices of sympathetic and parasympathetic nervous system activity simultaneously in relationship to inflammatory markers in apparently healthy adults. Therefore, the objective of this study was to assess the immunomodulatory effects of the ANS.

METHODS AND RESULTS:

The study population comprised 611 apparently healthy employees of an airplane manufacturing plant in southern Germany. Urinary NE was positively associated with white blood cell count (WBC) in the total sample. We found an inverse association between indices of vagally mediated heart rate variability and plasma levels of (CRP), which was significantly larger in females than in males after controlling for relevant covariates including NE. Similar results were found using the percentage of interbeat interval differences >50 ms and WBC.

CONCLUSIONS:

We report here for the first time, in a large sample of healthy human adults, evidence supporting the hypothesis of a clinically relevant cholinergic anti-inflammatory pathway after controlling for sympathetic nervous system activity. This suggests an important role for the vagal control of systemic inflammatory activity in cardiovascular disease.

Loss of vagal tone aggravates systemic inflammation and cardiac impairment in endotoxemic rats.

Nevner at manglende vagusfunksjon øker symptomene på akutt systemisk betennelse.

http://www.ncbi.nlm.nih.gov/pubmed/24565505

BACKGROUND:

During the course of sepsis, often myocardial depression with hemodynamic impairment occurs. Acetylcholine, the main transmitter of the parasympathetic Nervus vagus, has been shown to be of importance for the transmission of signals within the immune system and also for a variety of other functions throughout the organism. Hypothesizing a potential correlation between this dysfunction and hemodynamic impairment, we wanted to assess the impact of vagal stimulation on myocardial inflammation and function in a rat model of lipopolysaccharide (LPS)-induced septic shock. As the myocardial tissue is (sparsely) innervated by the N. vagus, there might be an important anti-inflammatory effect in the heart, inhibiting proinflammatory gene expression in cardiomyocytes and improving cardiac function.

MATERIALS AND METHODS:

We performed stimulation of the right cervical branch of the N. vagus in vagotomized, endotoxemic (1 mg/kg body weight LPS, intravenously) rats. Hemodynamic parameters were assessed over time using a left ventricular pressure-volume catheter. After the experiments, hearts and blood plasma were collected, and the expression of proinflammatory cytokines was measured using quantitative reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay.

RESULTS:

After vagotomy, the inflammatory response was aggravated, measurable by elevated cytokine levels in plasma and ventricular tissue. In concordance, cardiac impairment during septic shock was pronounced in these animals. To reverse both hemodynamic and immunologic effects of diminished vagal tone, even a brief stimulation of the N. vagus was enough during initial LPS infusion.

CONCLUSIONS:

Overall, the N. vagus might play a major role in maintaining hemodynamic stability and cardiac immune homeostasis during septic shock.

The relationship between heart rate variability and inflammatory markers in cardiovascular diseases.

Om hvrodan lav HRV bidrar til hjerte/kar problematikk og betennelser.

http://www.ncbi.nlm.nih.gov/pubmed/18819754

INTRODUCTION:

Recent evidence implicates a cholinergic anti-inflammatory pathway. Because vagus nerve activity mediates some heart rate variability (HRV), this qualitative review examines the literature concerning circulating cytokines and HRV in cardiovascular function in humans. This qualitative review examines the literature concerning circulating cytokines and HRV in cardiovascular function in humans.

METHODS:

Thirteen studies on HRV, inflammation, and cardiovascular function were located by electronic library search and descriptively reviewed.

RESULTS:

The relationship between HRV and inflammation was studied in healthy controls, patients with acute or stable coronary heart disease (CHD), patients with metabolic syndrome or impaired glucose tolerance and patients with kidney failure. Investigations focused mainly on Interleukin-6 (IL-6) and C-reactive peptide (CRP). The majority of reviewed studies reported that parasympathetic nervous system tone as inferred from heart rate variability is inversely related to inflammatory markers (r values between -0.2 and -0.4). The relationships with inflammatory markers were similar whether derived from ECG signals as short as 5-30min or from 24-h ECG readings for HRV analyses. While inflammatory markers appear to be related to HRV, it is a mistake to assume that the traditional «vagal measures» of HRV (such as high frequency heart rate variability) are the driving factors. Indeed, low frequency heart rate variability, a complex measure reflecting both parasympathetic and sympathetic activity, is the more commonly associated measure linked to inflammatory markers.

DISCUSSION:

Heart rate variability is inversely correlated with inflammatory markers in healthy individuals as well as in those with cardiovascular diseases.