Stretch Receptors Research Articles

Erratum for the Research Article, "A vibrating ingestible bioelectronic stimulator modulates gastric stretch receptors for illusory satiety" by S. S. Srinivasan et al.

Erratum for the Research Article, "A vibrating ingestible bioelectronic stimulator modulates gastric stretch receptors for illusory satiety" by S. S. Srinivasan et al.

A Critical Examination of Ligamentous Pathogenesis of Bladder Pain/Lower Urinary Tract Symptoms Using the UEDA Criteria.

To critically analyse the relationship of bladder pain syndrome (BPS/IC), as defined, to the posterior fornix syndrome, "PFS" predictably co-occurring bladder urgency, frequency, nocturia, chronic pelvic pain, emptying symptoms/retention, caused by uterosacral ligament (USL) laxity and cured by USL repair. The starting and end points of this paper are the questions, "Are there arguments that BPS/IC can, in some cases, be linked to PFS?" And if so, "To what extent?" We used the criteria required by Ueda for proper diagnosis: "understanding symptoms, detecting abnormal findings and verifying them as a cause of the symptoms." Literature, diagnostic and surgical, indicate that chronic pelvic pain "of unknown origin" can be caused by unsupported visceral pelvic plexuses because of weak USLs; these cause fire of afferent impulses, which the brain mistakenly interprets as coming from the end-organ itself (i.e., genitourinary pain, lower urinary tract symptoms). The same lax USLs can also weaken the pelvic muscles which contract to stretch the vagina to support the urothelial stretch receptors from below: these may prematurely fire off afferent impulses to activate micturition at lower bladder volumes, interpreted as urgency. A speculum placed in the vagina can relieve pain and urgency by mechanically supporting the vaginal wall and USLs, thus predicting an eventual cure by USL repair. There is need to evaluate what percentage of women with known BPS/IC also pass the criteria for PFS. Identifying a significant percentage of BPS/IC women with the causative relation between PFS pathogenesis and BPS/ IC may open a new way of diagnosing and treating BPS/IC in some women.

Cardiac Contractility Drives Cardiac Interoception

Introduction: Many of the receptors for the exteroceptive senses (e.g. vision, hearing, smell, touch, pain, etc.) are known. Interoception allows us to sense threats to our “milieu interior.” The mechanisms by which threats induce a feeling of anxiety manifested by heart palpitations, shortness of breath (dyspnea), and gastric awareness (queasiness) are unknown. Using photoplethysmography, we reported that individual variation in cardiac interoception, i.e. the ability to feel a change in one’s heartbeat without taking one’s pulse, correlated with contrasts in heart rate and stroke volumes among the population. Hypothesis: Because increases in heart rate and stroke volume raise cardiac contractility, we postulated that stretch activated piezo channels in the heart are responsible for cardiac interoception. Methods: Interoceptive awareness was determined with a ten point Likert scale in which volunteers rated their ability to feel their heartbeat. Interoceptive accuracy was measured by asking subjects to count their heartbeats without taking their pulse over four time intervals in random order. Simultaneously, heart rates were surreptitiously recorded with a two lead electrocardiogram (EKG). Cardiac interoceptive accuracy was calculated using the formula 1/4 Σ [1 − (|EKG measured heartbeats − subjectively reported heartbeats|) / EKG measured heartbeats]. We used 2D speckle tracking ultrasound to measure the relationship between cardiac strain patterns, normalized for heart rate (HR) and body surface area (BSA), and cardiac interoception in 12 resting men and women. We also measured gastric interoception by determining the percent increase in the volume of water some subjects could drink after reporting water satiety. Results: Cardiac interoceptive awareness correlated with interoceptive accuracy ( r = 0.73, p = 0.009). Speckle tracking of cardiac chambers with echocardiography demonstrated that global longitudinal left ventricular (LV) strain correlated with total left ventricular preload (atrial reservoir strain, r = 0.83, p = 0.0009) and early diastolic filling (atrial conduit strain, r = 0.88, p = 0.0002). LV strain also correlated with interoceptive awareness ( r = 0.58, p = 0.046). When stratified, individuals with the highest interoceptive accuracy (n = 6), compared to those with the lowest interoceptive accuracy (n = 6), had less LV strain, [values expressed as (percent change/BSA)*HR ± S.E.M., 828 ± 81 vs. 582 ± 47, p = 0.026]. Cardiac interoceptive awareness also correlated with gastric interoception accuracy, (n = 6) r = 0.90, p = 0.015. Conclusions: Changes in the activation of cardiac stretch receptors by cardiac filling and contractility could modify interoceptive awareness in men and women at rest. Contrasts in stretch receptor activation in other contractile organs (e.g. stomach) could explain variation in interoceptive awareness in the population. Henry M. Jackson Foundation for the Advancement of Military Medicine. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

How stretching a glove (the vagina and urothelial stretch receptors) by opposite forces reduces the weight impacting on the glove (vagina, and urothelial stretch receptors).

How stretching a glove (the vagina and urothelial stretch receptors) by opposite forces reduces the weight impacting on the glove (vagina, and urothelial stretch receptors).

Respiration and Cough in Pompe Disease: Results from a neuromechanical computational model of the respiratory control system

Late Onset Pompe Disease (LOPD) is an incurable, rare progressive genetic disease. It is characterized by glycogen build-up, due to mutations in the gene encoding the lysosomal enzyme acid alpha glucosidase, throughout muscle and neural regions. This accumulation is associated with cell death and muscle fiber swelling, eventually leading to respiratory insuffciency and airway clearance (i.e. cough) deficiency. Impairments in effective airway clearance result from the inability to clear normal pulmonary volume. Emerging evidence indicates significant respiratory neuron dysfunction, altering pulmonary function in humans and animal models. It has been suggested that respiratory and airway clearance insuffciency observed in LOPD may be attributed to medullary motoneurons potentially associated with the respiratory and cough pattern generators (Fuller et al., 2013; DeRuisseau et al., 2009). However, the precise neural mechanisms that suppress breathing and cough are not fully understood. One possible target for LOPD respiratory insuffciencies may be reduced medullary inspiratory neuron activity within this network, which could result in decreased phrenic motoneuron output. Using a stochastic neural network simulator that consisted of discrete “integrate and fire” populations, we simulated a systematic decrease in three medullary inspiratory neuron populations: inspiratory driver (I-Driver), inspiratory decrementing (I-Dec), or inspiratory augmenting (I-Aug) neurons. We simulated breathing and three cough trials. By targeting these populations, we expected global decreased neural bursts, suppressed inspiratory motor drive, and/or suppressed expiratory motoneuron output. Simulations indicated that when the I-Dec motoneuron population decreased by 25%, it resulted in apnea and abolished cough. Reducing the I-Aug motoneuron population by 20% resulted in longer inspiratory phase durations (TI) and a decreased respiratory rate. During cough, there was a decrease in the duration and amplitudes of the expiratory motoneuronal activity associated with decreased cough receptor and pulmonary stretch receptor afferent feedback. When the I-Driver motoneuron population was reduced by 25%, TI decreased and I amplitude increased during respiration. During cough, lumbar and phrenic motoneuron discharge duration and amplitude decreased. These results are consistent with previously reported in vivo data. Overall, our simulation data support the plausibility of glycogen storage dysfunction impairing medullary neuronal and premotoneuronal excitability within the inspiratory network. Our results also suggest that some neurons may be more sensitive to glycogen storage than others within the brainstem inspiratory network. Supported by NHLBI L30HL165496, NIH T32 HL 134621 and 3OT2OD023854. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Stimuli factor of muscular receptors, extraocular muscles and oculocardiac reflex (OCR)

Introduction: The oculocardiac reflex (OCR) was first described in 1908 as a reduction in heart rate secondary to direct pressure on the eyeball. OCR has been described during ophthalmologic procedures. This is also a standard test for peripherical autonomic and vagal system with the diving reflex and overtraining. The aim studied the specificities of stimuli of stretch receptors wich can be the traction at the extraocular muscles. Materials: 7 rabbits were included on the study. The anesthesia was done by an Intraperitoneal administration of ethyl carbamate. During all the study the rabbit is immobilized with a gripping frame for the head. Heart rate and RR were measured with EKG was recorded online. Methods: Bilateral pressure is applied using a mechanical pressure compression device, ranging from 100 to 800 mmHg, either instantaneously or in 15 or 30 seconds. For each pression we studied the variations of the RRspace (RRmax and RRt function of time) compared with the RRcontrol. If no variation, RRmax/RRcontrol and RRt/RRcontrol =1 Results: Response to abrupt compression RRmax varied linearly and significantly with pression. Response to progressive compression did not show any significant variation either during rise of pressure or when pressure was reached. Time-based response was studied from 56RR intervals. With abrut compression, the increase was effective from the first or second RR intervals. Depending on the pressure, it increased up to the 20th, presented a peak and decreased even with maintained pressure. The RR interval reverted to the control (RR/tRR = 1) around the 40th interval. With progressive stimulation, the maximum elongation value is lower, with an identical decay. Discussion: Our work showed the characteristics of stimulating factor: we used pressure on eyeballs, as in a sports medicine test (cardiac parasympathetic analysis) and in emergencies for the reduction of arrhythmias. This principal factor is tension in function of time, with an elongation of the periorbital muscles and the neuromuscular spindle. This is a proprioceptive sensory mecano-receptor sensitive to elongation. It is made up of primary neuromuscular fibers known as nuclear sac fibers and secondary neuromuscular fibers known as nuclear chain fibers. The former are 'phasic' (i.e. reacting to a variation in tension) and the latter 'tonic' (i.e. reacting directly to tension). Our work showed that the neuromuscular fibers of the nuclear sac type are stimulated by variations in tension as a function of time. Platen (1961) in ocular surgery introduced the notion of traction on the oculomotor muscles. In ‘OpenAnesthesia 2023’ Dennath Chatterjee did a synthesis work in the traction and anesthesia factors. In sports medicine, the dive reflex has been shown to be responsable of arythmia and paroxysmal supraventricular tachycardia. To trigger this reflex, several tests have beeen proposed. A recommandation during clinical examination is the OCR or Carotid glomus massage, with record of EKG and cardiac frequency. Conclusion: The OCR is defined by a reduction in heart rate from direct pressure on the eyeball. Afferent and efferent pathways are known and studied. But the stimulating factor must be studied. We have demontred that is the elongation of neuro-muscular fibers according to the time that excites the phasic fibers. This notion must be integrated both in eye surgery and in tests to highlight the cardiac parasympathetic balance, especially in sports physiology. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

A brief physiology and pathophysiology of the anorectum based on the Integral Theory paradigm.

The remit of this review is confined to the experimental scientific works and surgeries based on the Integral Theory paradigm. The video abstract summarizes the anorectal function, how ligaments cause dysfunction and cure of fecal incontinence and obstructed defecation by ligament repair. Anorectal function is reflex and binary, with cortical and peripheral components. The same three oppositely acting reflex muscle forces which open and close the bladder, contract against the pubourethral (PUL) and uterosacral (USL) ligaments: (I) to close the anorectum for continence when the puborectalis muscle (PRM) contracts forwards; (II) to open the anorectum prior to evacuation when the PRM relaxes; (III) to stretch the rectum in opposite directions to support the anorectal stretch receptors "N" to prevent premature activation of the defecation reflex, (fecal urgency). Weak or loose PULs or USLs may cause dysfunction of closure, of evacuation, and inability to control the defecation reflex (fecal urgency). Repair of the PUL and USL can improve or cure these dysfunctions. The perineal body (PB) acts as an anatomical support for the distal vagina, anorectum and external anal sphincter (EAS). It serves as an anchoring point for the forward action of the pubococcygeus muscle (PCM), which tensions the anterior rectal wall during closure and defecation. Bladder and bowel dysfunction have a similar pathogenesis, ligament laxity, mainly pubourethral and uterosacral, with added PB damage for anorectal dysfunction. PB damage can cause obstructive defecation and descending perineal syndrome (DPS). Repair of damaged PUL and USL can restore the closure and evacuation functions of both bladder an anorectum. DPS can be cured by repair of the PB's suspensory ligaments, deep transversus perinei.

Peripheral muscle force balance/imbalance in neurological binary control of bladder function and dysfunction.

Bladder control is not from the bladder itself but from muscles and ligaments outside of it. Bladder control is binary, either closed or open. Control is exerted cortically, directly and via a peripheral pelvic mechanism comprising three reflex pelvic muscles which contract (variously) against pubourethral ligaments (PULs) anteriorly and uterosacral ligaments (USLs) posteriorly. Directed efferent impulses from the cortex close the urethra, open it, and stretch the vagina in opposite directions to prevent urothelial impulses inappropriately activating micturition (urge incontinence). Normally, the opposite muscles are equivalent in force, and balance at the bladder neck. Weak PULs weaken the forward closure force: the posterior forces become relatively more powerful; balance shifts behind bladder neck; the posterior urethral wall is pulled open like a trapdoor, and urine is lost on effort (stress urinary incontinence). Weak USLs weaken the posterior muscle forces; the balance of forces shifts forwards, and the urethra is closed relatively more tightly by slow-twitch forward muscle vector forces (pubococcygei), which stretch each side of the distal vagina forwards to compress the posterior urethral wall; in consequence, the weakened posterior muscle forces cannot easily open the posterior urethral wall; the bladder has to contract against a relatively unopened urethra, perceived as "obstructed micturition". Nor can weakened posterior forces stretch the vagina sufficiently to support the urothelial stretch receptors from below; these may fire off excess afferent impulses to cause urgency. As bladder control is strictly binary, in women with urgency, control swings between open and closed modes. This condition is known as an "unstable bladder", which is defined symptomatically as "overactive bladder", and urodynamically as "detrusor overactivity". In summary, bladder control is binary, either closed or open. How the cortex integrates and computes multiple inputs determines the type of closure, opening or unstable control which is experienced by the patient.

A brief physiology and pathophysiology of the bladder.

The remit of this review is confined to experimental works and publications relevant to the integral theory of female urinary incontinence (IT). Since its first publication in 1990, the IT has challenged the general view that the pathogenesis of overactive bladder (OAB) (urge, frequency, nocturia) is unknown and there is no cure. According to the IT, normal function bladder control is binary, either closed or open. Control is cortical via a peripheral feedback component: oppositely acting reflex striated pelvic muscles contract against suspensory ligaments to close the urethra for continence, open it prior to evacuation, and stretch the vagina like a trampoline to prevent excess impulses from the urothelial stretch receptors which may cause unwanted urgency at low bladder volumes (OAB). The pathogenesis of female urinary incontinence is from outside the bladder, mainly weak ligaments or vagina, due to collagen deficiency. Damage in childbirth (collagen depolymerization) and age (collagen loss) make ligaments vulnerable to damage. With weak ligaments, muscles contracting against them weaken: the muscles cannot close the urethra (manifested as stress incontinence), open it (manifested as emptying problems or retention) or stretch the vagina to prevent the urothelial stretch receptors firing off prematurely (manifested as urge incontinence). Weak pubourethral ligaments can cause stress urinary incontinence (SUI), or SUI plus urge (mixed incontinence). Weak uterosacral ligaments (USLs) can cause urge, frequency, nocturia and emptying difficulties. Treatment consisting of surgical/non-surgical strengthening of ligaments can cure or improve SUI, OAB, and emptying dysfunctions. In summary, bladder control is from outside the bladder, binary, with cortical and peripheral components. A small change in definition, from "overactive" to "overactivated" is consistent with this concept, retains the acronym "OAB", and opens the door to probability of cure and a massive increase in research endeavours.

Interstitial cystitis/bladder pain syndrome: when part of the posterior fornix syndrome is potentially curable surgically.

Interstitial cystitis/bladder pain syndrome (IC/BPS) is defined as chronic pelvic pain plus a bladder symptom, usually urge. Evidence is offered to show IC/BPS forms part of the posterior fornix syndrome (PFS), which was defined in 1993 as: chronic pelvic pain (CPP), urge, frequency, nocturia, abnormal emptying, post-void residual urine, caused by uterosacral ligament (USL) laxity and cured or improved by USL repair. The IC/BPS definition implies that the urge and pain of IC/BPS is from a single (as yet unknown) pathogenic origin. However, when urge and pain are viewed from the perspective of the PFS, though both have the same lax USL origin, the anatomical pathway from lax USL to symptom manifestation is very different manifestation. For CPP the anatomical pathway is the inability of loose USLs to support pelvic visceral plexuses (VPs); it is hypothesized that inability of weak USLs to mechanically supports VPs, the afferent nerve synapse from end organs may fire off autologous afferent impulses to the brain which interprets them as pain from end organs such as urothelium, vulva, lower abdomen. For urge, the anatomical pathway is very different: lax USLs weaken the directional pelvic muscle forces which stretch the vagina to support the urothelial stretch receptors. The receptors fire off afferent impulses to the cortex at a lower bladder volume, and these are interpreted as "urge to go". Mechanical support of USLs relieves both pain and urge, as does USL repair.

A vibrating ingestible bioelectronic stimulator modulates gastric stretch receptors for illusory satiety.

Effective therapies for obesity require invasive surgical and endoscopic interventions or high patient adherence, making it challenging for patients with obesity to effectively manage their disease. Gastric mechanoreceptors sense distension of the stomach and perform volume-dependent vagal signaling to initiate the gastric phase and influence satiety. In this study, we developed a new luminal stimulation modality to specifically activate these gastric stretch receptors to elicit a vagal afferent response commensurate with mechanical distension. We designed the Vibrating Ingestible BioElectronic Stimulator (VIBES) pill, an ingestible device that performs luminal vibratory stimulation to activate mechanoreceptors and stroke mucosal receptors, which induces serotonin release and yields a hormonal metabolic response commensurate with a fed state. We evaluated VIBES across 108 meals in swine which consistently led to diminished food intake (~40%, P < 0.0001) and minimized the weight gain rate (P < 0.05) as compared to untreated controls. Application of mechanoreceptor biology could transform our capacity to help patients suffering from nutritional disorders.

Exerted force on the face mask in preterm infants at birth is associated with apnoea and bradycardia

BackgroundDuring stabilisation of preterm infants at birth, a face mask is used to provide respiratory support. However, application of these masks may activate cutaneous stretch receptors of the trigeminal nerve, causing apnoea and bradycardia. This study investigated the amount of force exerted on the face mask during non-invasive ventilation of preterm infants at birth and whether the amount of exerted force is associated with apnoea and bradycardia. MethodsA prospective observational study was performed in preterm infants born <32 weeks of gestation who were stabilised at birth. During the first 10 minutes of respiratory support, we measured breathing and heart rate as well as the amount of force exerted on a face mask using a custom-made pressure sensor placed on top of the face mask. ResultsThirty infants were included (median (IQR) gestational age(GA) 28+3 (27+0–30+0) weeks, birthweight 1104 (878–1275) grams). The median exerted force measured was 297 (198–377) grams, ranging from 0 to 1455 grams. Significantly more force was exerted on the face mask during positive pressure ventilation when compared to CPAP (410 (256–556) vs 286 (190–373) grams, p = 0.009).In a binary logistic regression model, higher forces were associated with an increased risk of apnoea (OR = 1.607 (1.556–1.661), p < 0.001) and bradycardia (OR = 1.140 (1.102–1.180), p < 0.001) during the first 10 minutes of respiratory support at birth. ConclusionDuring mask ventilation, the median exerted force on a face mask was 297 grams with a maximum of 1455 grams. Higher exerted forces were associated apnoea and bradycardia during the first 10 minutes of respiratory support at birth.

Interoceptive Awareness Among the General Public in Saudi Arabia: A Cross-Sectional Study.

Background Interoception refers to the cognitive process of perceiving internal bodily states. This encompasses various physiological indicators, including heart rate fluctuations, stomach distention, internal temperature, hydration levels, sensory input from free nerve terminals in the fascia and muscles, as well as hormonal, stretch, and pain receptors. This study aimed to examine the interoceptive awareness among the general public in Saudi Arabia. Methods A cross-sectional online survey was undertaken in Saudi Arabia to investigate the level of interoceptive awareness within the overall population of the country in October 2023. This research used a previously developed questionnaire named the Multidimensional Assessment of Interoceptive Awareness, version 2 (MAIA-2). In a binary logistic regression analysis, the mean interoceptive awareness score of the participants was utilized as the dummy variable to determine the variables that influence interoceptive awareness. Results A total of 814 participants were involved in this study. Overall, the study participants demonstrated a marginal level of interoceptive awareness with a mean score of 94.3 (standard deviation (SD): 29.3) out of 185 (representing 51.0% of the maximum attainable score). The mean interoceptive score was not consistent across different subscales and ranged between 37.7% and 63.3%. The highest mean interoceptive score was observed for the Trusting subscale (9.5 (SD: 4.5) out of 15) (representing 63.3% of the maximum attainable score for this subscale). The lowest mean interoceptive score was observed for the Not-Distracting subscale (11.3 (SD: 6.9) out of 30) (representing 37.7% of the maximum attainable score for this subscale). Binary logistic regression analysis did not identify any statistically significant difference in the likelihood of having a higher level of interoceptive awareness among the participants based on their demographic characteristics (p>0.05). Conclusion The participants in our research demonstrated a modest degree of interoceptive awareness. The study's results suggest that the participants demonstrated a heightened inclination towards internal experiences rather than being attentive to their bodily sensations. Further investigation is required to examine interoceptive awareness across various cohorts.

The Food-Crushing Reflex and Its Inhibition

Anterior tooth (ANT) contacts induce a short-latency reflex inhibition of the human jaw-closing muscles. The jaw is a rigid class 1 lever for pinpoint targeting muscle force into a single bite point, the pivoting food particle. Seesaw reflex movements around the food particle fulcrum multiply the food-crushing force. Unpredictable jolts of reaction force caused by food crushing are subjected to the rostral ANT and caudally to the two articulate ends of the jaw triangle. The compression/distraction strains of food crushing must be monitored and inhibited by withdrawal reflexes. The mesencephalic ganglion (Vmes), neural myelin sheath, and muscle stretch receptors evolved subsequently to the advent of jaws to improve the velocity of proprioceptive and withdrawal reflexes. In mammalians, the spindles of the taut motor units, stretched by the food fulcrum, send excitatory monosynaptic feedback for the efferent neurons of the respective ipsilateral muscle units via the Vmes. In the Vmes, the spindle-input-mediating afferent neurons are coupled with another source of afferent feedback, which is also excitatory, from the back tooth (BAT) mechanoreceptors. The two sources of excitatory pulses are summated and targeted for the efferent neurons to boost the stretched and taut motor units. Likewise, the afferent feedback from the ANT mechanoreceptors is also coupled in the Vmes with concomitant feedback from spindles. The ANT output, however, is inhibitory to negate the excitatory feedback from the stretched jaw muscle units. The inhibitory feed from the anterior teeth temporarily blocks the excitatory potential of the masticatory motor efferent neurons to protect the anterior teeth and jaw joints from inadvertent strains. The inhibitory inputs from the anterior teeth alternate with the excitatory inputs from the BAT to determine which jaw-closing muscle units are activated or inhibited at any given instant of food crushing. The Vmes exists in all jawed vertebrates, and its evolution was probably motivated by demands for the control of bite force. The monosynaptic unilateral food-crushing excitatory and inhibitory reflexes (UFCRs) override the coexisting bilaterally executed feed for the jaw muscles from the central nervous system. The hypothesis proposed in this study is that the Vmes-mediated UFCRs combine neural inputs from tooth contacts with concomitant feedback from the muscle stretch receptors for the control of the mammalian food-crushing bite force.

Sharbat Zoofa Murakkab, A Promising Unani Formulation for Sual (Cough)

It has been described that Sual (cough) is the movement of lungs to remove or reduce the painful stress on the lungs). Cough is a physiologically useful protective reflex that clears the respiratory tract. It occurs due to stimulation of chemo receptors in throat, respiratory passages or stretch receptors in the lungs. According to Unani scholars, Sual (cough) is an act by which Tabiyat removes Aziyat (irritating substances) from the lungs, cough with mucus and sputum. It affects mainly quality of life, works productivity and public health resources etc. The drugs available in the modern medicine produce more or less side effects in the human body. The Unani classical formulation is traditionally used for the treatment of cough, early stages of asthma and useful in bronchial Asthma, phlegmatic cough. Expel phlegm from the chest. It is used to clear mucus from the chest and clear chest congestion. It is 100% natural and vegetarian product. No side effects of Sharbat Zoofa Murakkab mentioned and reported in Unani classical literature and a clinical study was conducted by the Central Council for Research in Unani Medicine under Ministry of AYUSH, Government of India, more studies are required to validate the Pharmacopeial formulation on large scale.

Interaction of large artery stiffness and baroreceptor function explored through multiple measurement techniques - a pilot study.

Baroreceptors, sensors that play a role in controlling arterial blood pressure (BP), are mechanical stretch receptors located in the aortic arch and carotid sinuses. Factors affecting the degree of stretch in the vessel wall with BP, such as increased arterial stiffness, may compromise baroreceptor sensitivity (BRS) to BP changes. Yet, evidence of this is scattered, as both baroreceptor sensitivity (BRS) and arterial stiffness are calculated variables with multiple methodological approaches. This pilot study (n=10) investigates the correlation of arterial stiffness and BRS using multiple BRS calculation techniques (spectral and sequence methodologies at aortic and finger sites) and arterial stiffness measurement [carotid-femoral pulse wave velocity (cfPWV), carotid compliance and distensibility]. BRS was assessed under resting BP conditions and during BP altered by maneuvers (0.1 Hz controlled breathing and leg ischemia). Magnitude of arterial stiffness - BRS correlation was positive for carotid distensibility and compliance, and negative for cfPWV, supporting the theory. A sample size of 100 participants (not rounded - exact figure by power calculation) would be required to confirm or reject all permutations of correlation between BRS by multiple calculation methods and large artery stiffness by PWV and compliance/distensibility measures.

Daily heart rate variability biofeedback practice sessions affect plasma Αβ40 and Αβ42 levels in healthy younger and older adults: A randomized clinical trial (N = 108)

AbstractBackgroundGenetic mutations affecting β‐amyloid (Αβ) production suggest that decreasing Αβ levels in healthy adults could prevent AD. However, evidence for behavioral interventions that decrease Αβ levels is lacking. The current study examined whether heart rate variability (HRV) biofeedback affects plasma Αβ levels. This intervention involves breathing slowly at a pace that maximizes the amplitude of heart rate oscillations. During slow paced breathing, the vagus nerve receives strong signals from stretch receptors in blood vessels and the lungs. These afferent signals stimulate ascending vagus nerve signaling that activate ‘safety’ signaling pathways, suppressing stress and arousal pathways in the brain and body. Experiencing adversity increases production of Aβ and risk of AD. We hypothesized that, in healthy adults, daily sessions involving slow paced breathing during HRV biofeedback could decrease Aβ by suppressing these adversity‐related processes.MethodHealthy adults (N = 54 age 18‐35; N = 54 age 55‐80) practiced HRV biofeedback daily for five weeks. They were randomized to use slow paced breathing and HRV biofeedback to increase heart rate oscillations (Osc+ condition) or to use personalized strategies and HRV biofeedback to try to decrease heart rate oscillations (Osc‐ condition). Pre‐ and post‐intervention plasma Aβ40 and Aβ42 levels were quantified blind to condition. Gene expression analysis of peripheral blood samples of the 54 younger adults using bioinformatics‐based analyses of genome‐wide RNA profiles examined activity of pro‐inflammatory, neuroendocrine, and antiviral transcription control pathways relevant to the conserved transcriptional response to adversity (CTRA). We predicted that reductions in the CTRA across the 5‐week trial would be associated with reduced plasma Aβ.ResultBoth younger and older adults showed significant differences between Osc+ and Osc‐ conditions in change in plasma Aβ40 and Aβ42 levels (Figure 1). The Osc+ condition decreased Αβ while the Osc‐ condition increased Αβ. Individual changes in plasma Aβ from pre‐ to post‐intervention were associated with changes in expression of the CTRA in the predicted direction.ConclusionHRV biofeedback affects plasma Aβ and these effects are associated with changes in expression of genes upregulated during adversity. Future longer‐term studies should test whether reducing plasma Αβ via the Osc+ intervention reduces risk of developing AD.

A systematic review of HRV during diving in very cold water

ABSTRACT Heart rate variability (HRV) is a useful method to study the autonomic nervous system (ANS) status. As measuring devices have developed and become smaller, many researchers have become interested in the possibilities to implement the method for diving medicine research. The aim of this study was to review human ANS responses in cold water diving (water temperature <5°C), and to comprise the current knowledge of HRV studies in diving and hyperbaric exposure into one review article. A literature search was conducted on 5 Decemberth 2022, with the search terms “HRV” or “heart rate variability” and “diving” or “diver” or “divers”, with search functions of the data bases PubMed and Ovid Medline. Peer reviewed original articles, review articles and case reports were accepted to this review. Twenty-six articles met the pre-defined criteria and were included in this review. Studies from very cold water conditions were rare, but suggested that cold strengthens the ANS responses of diving – especially parasympathetic nervous system (PNS) activity due to the trigeminocardiac reflex and baroreceptor and cardiac stretch receptor activity, caused cold and pressure-induced centralisation of the blood. Overall, studies showed predominant PNS activity when putting the face in water, during immersion and when ambient pressure increased.

Modulation of Cerebral Function by Muscle Afferent Activity, with Reference to Intravenous Succinylcholine.

Cerebral Function and Muscle Afferent Activity Following Intravenous Succinylcholine in Dogs Anesthetized with Halothane: The Effects of Pretreatment with a Defasciculating Dose of Pancuronium. By WL Lanier, PA Iaizzo, and JH Milde. Anesthesiology 1989; 71:87-95. Reprinted with permission. By the mid-1980s, it was widely assumed that if the depolarizing muscle relaxant, succinylcholine, given IV, produced increases in intracranial pressure, it did so because fasciculations produced increases in intrathoracic and central venous pressures that were transferred to the brain; however, there was no direct evidence that this was true. In contrast, we explored the possibility that the succinylcholine effect on the brain was explained by the afferentation theory of cerebral arousal, which predicts that agents or maneuvers that stimulate muscle stretch receptors will tend to stimulate the brain. Our research in tracheally intubated, lightly anesthetized dogs discovered that IV succinylcholine (which does not cross the blood-brain barrier) produced a doubling of cerebral blood flow that lasted for 30 min and corresponded to activation of the electroencephalogram and increases in intracranial pressure. Later, in our Classic Paper, we were able to assess simultaneously cerebral physiology and afferent nerve traffic emanating from muscle stretch receptors (primarily muscle spindles). We affirmed that the cerebral arousal response to succinylcholine was indeed driven by muscle afferent traffic and was independent of fasciculations or increases in intrathoracic or central venous pressures. Later research in complementary models demonstrated that endogenous movement (e.g., coughing, hiccups) produced a cerebral response very similar to IV succinylcholine, apparently as a result of the same muscle afferent mechanisms, independent of intrathoracic and central venous pressures. Thus, the importance of afferentation theory as a driver of the cerebral state of arousal and cerebral physiology during anesthesia was affirmed.

Reply to "Interstitial Cystitis - A Consequence of Weakened Uterosacral Ligaments Failing to Support Visceral Plexuses and Bladder Stretch Receptors and Therefore Potentially Curable?"

See the letter "Interstitial Cystitis: A Consequence of Weakened Uterosacral Ligaments Failing to Support Visceral Plexuses and Bladder Stretch Receptors, and Therefore Potentially Curable?" on page 349.