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Typically, unit discharge of slowly adapting receptors (SARs) declines slowly when lung inflation pressure is constant, although in some units it increases instead—a phenomenon hereinafter referred to as creeping. These studies characterize creeping behavior observed in 62 of 137 SAR units examined in anesthetized, open-chest, and mechanically ventilated rabbits. SAR units recorded from the cervical vagus nerve were studied during 4 s of constant lung inflation at 10, 20, and 30 cmH2O. Affected SAR units creep more quickly as inflation pressure increases. SAR units also often deactivate after creeping, i.e., their activity decreases or stops completely. Creeping likely results from encoder switching from a low discharge to a high discharge SAR, because it disappears in SAR units with multiple receptive fields after blocking a high discharge encoder in one field leaves low discharge encoders intact. The results support that encoder switching is a common mechanism operating in lung mechanosensory units.

Conventional one-sensor theory (one afferent fiber connects to a single sensor) categorizes the bronchopulmonary mechanosensors into the rapidly adapting receptors (RARs), slowly adapting receptors (SARs), or intermediate adapting receptors (IARs). RARs and SARs are known to sense the rate and magnitude of mechanical change, respectively; however, there is no agreement on what IARs sense. Some investigators believe that the three types of sensors are actually one group with similar but different properties and IARs operate within that group. Other investigators (majority) believe IARs overlap with the RARs and SARs and can be classified within them according to their characteristics. Clearly, there is no consensus on IARs function. Recently, a multiple-sensor theory has been advanced in which a sensory unit may contain many heterogeneous sensors, such as both RARs and SARs. There are no IARs. Intermediate adapting unit behavior results from coexistence of RARs and SARs. Therefore, the unit can sense both rate and magnitude of changes. The purpose of this review is to provide evidence that the multiple-sensor theory better explains sensory unit behavior.

Mechanical stimulation of the stretch receptors of the gastric wall can simulate the presence of indigested food leading to reduced food intake. We report the preliminary experimental results of an innovative concept of localized mechanical gastric stimulation. In a first survival study, a biocompatible bulking agent was injected either in the greater curvature (n = 8) or in the cardia wall (n = 8) of Wistar rats. Six animals served as sham. Changes of bulking volume, leptin levels and weight gain were monitored for 3 months. In a second acute study, a micro-motor (n = 10; MM) or a size-paired inactive device (n = 10; ID) where applied on the cardia, while 10 additional rats served as sham. Serum ghrelin and leptin were measured at baseline and every hour (T0–T1–T2–T3), during 3 h. In a third study, 24 implants of various shapes and sizes were introduced into the gastric subserosa of 6 Yucatan pigs. Monthly CT scans and gastroscopies were done for 6 months. Weight gain in the CW group was significant lower after 2 weeks and 3 months when compared to the shame and GC (p = 0.01/p = 0.01 and p = 0.048/p = 0.038 respectively). Significant lower increase of leptin production occurred at 2 weeks (p = 0.01) and 3 months (p = 0.008) in CW vs. SG. In the MM group significant reduction of the serum ghrelin was seen after 3 h. Leptin was significantly increased in both MM and ID groups after 3 h, while it was significantly reduced in sham rats. The global device retention was 43.5%. Devices with lower profile and with a biocompatible coating remained more likely in place without complications. Gastric mechanical stimulation induced a reduced weight gain and hormonal changes. Low profile and coated devices inserted within the gastric wall are more likely to be integrated.

In our present studies, we seek to determine whether increased osmolarity stimulates deflation-activated receptors (DARs). In anesthetized, open-chest, and mechanically ventilated rabbits, we recorded single-unit activities from typical slowly adapting receptors (SARs; responding only to lung inflation) and DAR-containing SARs (DAR-SARs; responding to both lung inflation and deflation) and identified their receptive fields in the lung. We examined responses of these two groups of pulmonary sensory units to direct injection of hypertonic saline (8.1% sodium chloride; 9-fold in tonicity) into the receptive fields. Hypertonic saline decreased the activity in most SAR units from 40.3 ± 5.4 to 34.8 ± 4.7 imp/s ( P < 0.05, n = 12). In contrast, it increased the activity in DAR-SAR units quickly and significantly from 15.9 ± 2.2 to 43.4 ± 10.0 imp/s ( P < 0.01, n = 10). Many units initially had increased activity, mainly in the deflation phase. DAR-SAR activities largely returned to the control level 30 s after injection. Since hypertonic saline stimulated DAR-SAR units but not SAR units, we conclude that hypertonic saline activates DARs.

Pulmonary mechanosensory receptors provide important inputs to the respiratory center for control of breathing. However, what is known about their structure-function relationship is still limited. In these studies, we explored this relationship comparing bronchopulmonary slowly adapting receptor (SAR) units in rabbits and rats. In morphological studies, sensory units in tracheobronchial smooth muscle labeled with anti-Na

Aerosol furosemide may be an option to treat refractory dyspnea, though doses, methods of delivery, and outcomes have been variable. We hypothesized that controlled delivery of high dose aerosol furosemide would reduce variability of dyspnea relief in patients with underlying pulmonary disease. Seventeen patients with chronic exertional dyspnea were recruited. Patients rated recently recalled breathing discomfort on a numerical rating scale (NRS) and the multidimensional dyspnea profile (MDP). They then performed graded exercise using an arm-ergometer. The NRS was completed following each exercise grade, and the MDP was repeated after a pre-defined dyspnea threshold was reached. During separate visits, patients received either aerosol saline or 80 mg of aerosol furosemide in a randomized, double-blind, crossover design. After treatment, graded exercise to the pre-treatment level was repeated, followed by completion of the NRS and MDP. Treatment effect was defined as the difference between pre- and post-treatment NRS at end exercise, expressed in absolute terms as % Full Scale. “Responders” were defined as those showing treatment effect ≥ 20% of full scale. Final analysis included 15 patients. Neither treatment produced a statistically significant change in NRS and there was no significant difference between treatments (p = 0.45). There were four “responders” and one patient whose dyspnea worsened with furosemide; two patients were responders with saline, of whom one also responded to furosemide. No adverse events were reported. High dose controlled delivery aerosol furosemide was not statistically different from saline placebo at reducing exercise-induced dyspnea. However, a clinically meaningful improvement was noted in some patients.

Muscle cells are routinely subjected to mechanical stretch but the impact of stretch on the organization of membrane domains is unknown. In this study, we characterize the effect of stretch on GPCR-Gαq protein signaling. Activation of this pathway leads to an increase in intracellular calcium. In muscle cells, GPCR-Gαq signals are enhanced when these proteins are localized in caveolae membrane domains whose curved structure can flatten with stretch. When we statically stretch rat aortic smooth muscle A10 cells by 1–5%, cellular calcium appears unperturbed as indicated by a calcium indicator. However, when we activate the bradykinin type 2 receptor (B2R) / Gαq pathway, we observe a loss in calcium that appears to be mediated through perturbations in calcium-activated stretch receptors. In contrast, if we apply oscillating stretch calcium signals are enhanced. We tested whether the observed changes in B2R-Gαq calcium signals were caused by stretch-induced disruption of caveolae using a combination of silencing RNA technology and growth conditions. We find that stretch changes the ability of monoclonal caveolin antibodies to bind caveolae indicating a change in configuration of the domains. This change is seen by the inability of cells to survive stretch cycles when the level of caveolae is significantly reduced. Our studies show that the effect of calcium signals by mechanical stretch is mediated by the type of stretch and the amount of caveolae.

The recent outbreak of the novel coronavirus, SARS-CoV-2 has emerged to be highly pathogenic in nature. Although lungs are considered as the primary infected organs by SARS-CoV-2, some of the other organs including the brain have also been found to be affected. Here, we have discussed how SARS-CoV-2 might infect the brain. The infection of the respiratory center in the brainstem could be hypothesized to be responsible for the respiratory failure in many COVID-19 patients. The virus might gain entry through the olfactory bulb and invade various parts of the brain including the brainstem. Alternatively, entry might also occur from peripheral circulation into the central nervous system (CNS) by compromising the blood-brain barrier. Finally, yet another possible entry route could be its dispersal from the lungs into the vagus nerve, via the pulmonary stretch receptors, eventually reaching the brainstem. Therefore, screening neurological symptoms in COVID-19 patients, especially towards the breakdown of the respiratory center in the brainstem might help us better understand this disease. This article is protected by copyright. All rights reserved.

Bronchopulmonary mechanosensors play an important role in the regulation of breathing and airway defense. Regarding the mechanosensory unit, investigators have conventionally adhered to 2 doctrines: one-sensor theory (one afferent fiber connects to a single sensor) and line-labeled theory. Accordingly, lung inflation activates 2 types of mechanosensors: slowly adapting receptors (SARs) and rapidly adapting receptors (RARs) that also respond to lung deflation to produce Hering-Breuer deflation reflex. RARs send signals to a particular brain region to stimulate breathing (labeled as excitatory line) and SARs to a different region to inhibit breathing (inhibitory line). Conventionally, RARs are believed to be mechanosensors, but are also stimulated by a variety of chemicals and mediators. They are activated during different disease conditions and evoke various respiratory responses. In the literature, RARs are the most debatable sensors in the airway. Recent physiological and morphological studies demonstrate that a mechanosensory unit consists of numerous sensors with 4 types, i.e., an afferent fiber connects to multiple homogeneous or heterogeneous sensors (multiple-sensor theory). In addition to SARs and RARs, there are deflation-activated receptors (DARs), which can adapt slowly or rapidly. Each type senses a specific force and generates a unique response. For example, RAR (or SAR) units may respond to deflation if they house DARs responsible for the Hering-Breuer deflation reflex. Multiple-sensor theory requires a conceptual shift because 4 different types of information from numerous sensors carried in an afferent pathway violates conventional theories. Data generated over last eight decades under one-sensor theory require re-interpretation. Mechanosensors and their reflex functions need re-definition. This detailed review of the RARs represents our understanding of RARs under the conventional doctrines, thus it provides a very useful background for interpretation of RAR properties and reflex function against the new proposed multiple-sensor theory.

Cough is induced by mechanical and chemical (irritant) stimuli. The signal is carried out by the vagus nerve A-δ fibers from mechanosensitive cough receptors and/or from nonspecific C-fiber endings in the airways. Cough mechanosensors respond to punctate stimuli and rapid decrease of pH (acidic environment) in the airways providing crucial airway cleaning mechanism. Nonspecific chemosensors provide protection against irritant chemicals reaching lower respiratory tract. These are mostly responsible for upregulated cough response under pathological conditions. Besides primary cough afferent pathways numbers of other (secondary) afferents modulate cough including pulmonary stretch receptors, non-cough-related C-fibers of various origin, baroreceptors, etc. Moreover, several chemicals, neuromediators, and neuromodulators act on cough and other sensors to regulate and affect cough excitability and its motor pattern. Other motor behaviors including breathing, swallowing, sneezing, etc. interact with cough when they compete for the execution. The control neuronal mechanisms ensure under regular conditions that various behaviors order and execute appropriately. Interaction and cooperation of these motor acts may increase or reduce cough.

The dive response, bradycardia (decreased heart rate) and peripheral vasoconstriction, is the key mechanism allowing breath-hold divers to perform long-duration dives while actively swimming and hunting prey. This response is variable and modulated by factors such as dive duration, depth, exercise and cognitive control. This study assesses the potential role of exercise and relative lung volume in the regulation of heart rate (fH) during dives of adult female California sea lions instrumented with ECG, depth, and 3-axis acceleration data loggers. A positive relationship between activity (minimum specific acceleration) and fH throughout dives suggested increased muscle perfusion associated with exercise. However, apart from late ascent, fH during dives was still less than or equal to resting heart rate (on land). In addition, the activity-fH relationship was weaker in long, deep dives consistent with prioritization of blood oxygen conservation over blood oxygen delivery to muscle in those dives. Pulmonary stretch receptor reflexes may also contribute to fH regulation as fH profiles generally paralleled changes in relative lung volume, especially in shallower dives and during early descent and late ascent of deeper dives. Overall, these findings support the concept that both exercise and pulmonary stretch receptor reflexes may influence the dive response in sea lions.

Recurrent laryngeal afferent fibers are primarily responsible for cough in response to mechanical or chemical stimulation of the upper trachea and larynx in the guinea pig. Lower airway slowly adapting receptors have been proposed to have a permissive effect on the cough reflex. We hypothesized that vagotomy below the recurrent laryngeal nerve branch would depress mechanically or chemically induced cough. In anesthetized, bilaterally thoracotomized, artificially ventilated cats, thoracic vagotomy nearly eliminated cough induced by mechanical stimulation of the intrathoracic airway, significantly depressed mechanically stimulated laryngeal cough, and eliminated capsaicin-induced cough. These results support an important role of lower airway sensory feedback in the production of tracheobronchial and laryngeal cough in the cat. Further, at least some of this feedback is due to excitation from pulmonary volume-sensitive sensory receptors.

Background Acute respiratory distress syndrome (ARDS) is a severe form of lung injury characterized by damage to the epithelial barrier with subsequent pulmonary edema and hypoxic respiratory failure. ARDS is a significant medical problem in intensive care units with associated high care costs. There are many potential causes of ARDS; however, alveolar injury associated with mechanical ventilation, termed ventilator-induced lung injury (VILI), remains a well-recognized contributor. It is thus critical to understand the mechanism of VILI. Based on our published preliminary data, we hypothesized that the endoplasmic reticulum (ER) stress response molecule Protein Kinase R-like Endoplasmic Reticulum Kinase (PERK) plays a role in transmitting mechanosensory signals the alveolar epithelium. Methods ER stress signal responses to mechanical stretch were studied in ex-vivo ventilated pig lungs. To explore the effect of PERK inhibition on VILI, we ventilated live rats and compared lung injury parameters to non-ventilated controls. The effect of stretch-induced epithelial ER Ca2+ signaling on PERK was studied in stretched alveolar epithelial monolayers. To confirm the activation of PERK in human disease, ER stress signaling was compared between ARDS and non-ARDS lungs. Results Our studies revealed increased PERK-specific ER stress signaling in response to overstretch. PERK inhibition resulted in dose-dependent improvement of alveolar inflammation and permeability. Our data indicate that stretch-induced epithelial ER Ca2+ release is an activator of PERK. Experiments with human lung tissue confirmed PERK activation by ARDS. Conclusion Our study provides evidences that PERK is a mediator stretch signals in the alveolar epithelium.

Idiopathic pulmonary fibrosis (IPF) is a progressive disease characterized by excessive deposition of extracellular matrix (ECM) in the lung parenchyma. The abnormal ECM deposition slowly overtakes normal lung tissue, disturbing gas exchange and leading to respiratory failure and death. ECM cross-linking and subsequent stiffening is thought to be a major contributor of disease progression and also promotes the activation of transforming growth factor (TGF)-β1, one of the main profibrotic growth factors. Lysyl oxidase-like (LOXL) 1 belongs to the cross-linking enzyme family and has been shown to be up-regulated in active fibrotic regions of bleomycin-treated mice and patients with IPF. We demonstrate in this study that LOXL1-deficient mice are protected from experimental lung fibrosis induced by overexpression of TGF-β1 using adenoviral (Ad) gene transfer (AdTGF-β1). The lack of LOXL1 prevented accumulation of insoluble cross-linked collagen in the lungs, and therefore limited lung stiffness after AdTGF-β1. In addition, we applied mechanical stretch to lung slices from LOXL1+/+ and LOXL1-/- mice treated with AdTGF-β1. Lung stiffness (Young's modulus) of LOXL1-/- lung slices was significantly lower compared with LOXL1+/+ lung slices. Moreover, the release of activated TGF-β1 after mechanical stretch was significantly lower in LOXL1-/- mice compared with LOXL1+/+ mice after AdTGF-β1. These data support the concept that cross-linking enzyme inhibition represents an interesting therapeutic target for drug development in IPF.

In 1937, Drs. Moritz and Oldt described arteriolar injuries in the kidneys (and other viscera) in hypertension, across the age range, in both sexes, and, in different races. This hypothesis proposes that injuries to vasomotor nerves cause the arteriolar injury in the kidney in hypertension, (as well as that in the uterus in preeclampsia). Different patterns of perivascular hyalinisation in different viscera are clues to the varying causes and consequences of arteriolar injury. In the uterus there is a symmetrical, perivascular "halo of hyalinisation" that marks the lines of extension of regenerating, injured nerves to the placental bed, whereas in the kidney there is a disordered and asymmetrical "halo of hyalinisation" where persistent, and recurrent, increases in intravascular pressures interrupt development of regenerating nerves. Consequences of injuries to vasomotor nerves include releasing a "soup" of cytokines that cause regeneration of "new" nerves expressing primitive, pain and stretch receptors including TRPV-1 and P2X3 purinergic "stretch" receptors that may be significant in the afferent mechanism in preeclampsia. There is also concurrent, "background" hyperplasia of denervated tunica media and intima leading to narrowing of the arterioles and a further drive to hypertension through renal ischaemia (Goldblatt, 1942). These observations require support from animal studies and other investigations to establish causation. This hypothesis may provide a number of potential mechanisms that reinforce, or accelerate, the physiological processes that contribute to hypertension.

Medial parabrachial nucleus (mPBN) neuronal activity plays a key role in controlling expiratory (E)-duration (TE). Pulmonary stretch receptor (PSR) activity during the E-phase prolongs TE. The aims of this study were to characterize the interaction between the PSR and mPBN control of TE and underlying mechanisms. Decerebrated mechanically ventilated dogs were studied. The mPBN subregion was activated by electrical stimulation via bipolar microelectrode. PSR afferents were activated by low-level currents applied to the transected central vagus nerve. Both stimulus-frequency patterns during the E-phase were synchronized to the phrenic neurogram; TE was measured. A functional mathematical model for the control of TE and extracellular recordings from neurons in the preBötzinger/Bötzinger complex (preBC/BC) were used to understand mechanisms. Findings show that the mPBN gain-modulates, via attenuation, the PSR-mediated reflex. The model suggested functional sites for attenuation and neuronal data suggested correlates. The PSR- and PB-inputs appear to interact on E-decrementing neurons, which synaptically inhibit pre-I neurons, delaying the onset of the next I-phase.

The visceral pleura envelops the lung lobes. The visceral and parietal pleurae form the pleural cavity with negative pressure to keep the normal respiration possible. The lungs are complicatedly innervated by bilateral vagal and spinal nerves that have the sensory and motor components. Pulmonary vagal sensory receptors have been identified within the tissues in the extrapulmonary and intrapulmonary airways. However, vagal vs. spinal innervation in the pulmonary visceral pleura has been undecided. Mollgaard (1912) determined the neurons that innervate the lungs by whole or partial extirpation of the lung lobe. Larsell (1922) examined the vagal degeneration in the lungs and supported the vagal origin. However, Larsell and Coffey (1928) turned to the spinal origin when they inserted the balloon between the lung lobe and the chest wall or diaphragm and found no change in the rate and depth of inspiration. With vagotomy and excision of the second and third thoracic spinal ganglia, Honjin (1956) determined the vagal and rejected the spinal origin. With vagotomy, Pintelon and colleague (2007) identified non-vagal ＂visceral pleura receptors＂. Recently, we identified the classical hilar and novel non-hilar vagal pleural innervation pathways and two kinds of vagal nerve endings in the visceral pleura and triangular ligaments. Most of the areas that face the dorsal thoracic cavity have no vagal innervation, whereas the interlobar areas and those areas that face the heart receive bilateral or unilateral vagal innervation with a left-vagus-rostral-lung vs. right-vagus-caudal-lung lateralized innervation pattern. The experimental considerations and meanings for the vagal innervation pattern are discussed.

In normal humans, tapping the forehead produces a neck muscle reflex that is used clinically to test vestibular function, the cervical vestibular evoked myogenic potential (cVEMP). As stretch receptors can also be activated by skull taps, we investigated the origin of the early and late peaks of the bone-conducted cVEMP. In twelve normal participants, we differentially stimulated the vestibular and neck stretch receptors by applying vibration to the forehead (activating both vestibular and stretch receptors) and to the sternum (activating mainly stretch receptors). Patients with bilateral vestibulopathy (BVP; n = 26) and unilateral vestibular loss (uVL; n = 17) were also investigated for comparison. Comparison of peaks in normal subjects suggested that the early peaks were vestibular-dependent, while the later peaks had mixed vestibular and stretch input. The late peaks were present but small (1.1 amplitude ratio) in patients with BVP and absent VEMPs, confirming that they do not strictly depend on vestibular function, and largest in age-matched controls (1.5 amplitude ratio, p = 0.049), suggesting that there is an additional vestibular reflex at this latency (approx. 30 ms). Patients with uVL had larger late peaks on the affected than the normal side (1.4 vs 1.0 amplitude ratio, p = 0.034). The results suggest that the early responses in SCM to skull vibration in humans are vestibular-dependent, while there is a late stretch reflex bilaterally and a late vestibular reflex in the contralateral muscle.

Introduction: Inhibition of breathing elevates End-tidal Carbon dioxide (EtCO2 ) and contributes to sustained Hypertension (HT). Aim: To find out the immediate efficacy of Slow breathing (SB) in controlling Blood Pressure (BP) and its influence on EtCO2 in patients with hypertension. Materials and Methods: Randomised control parallel group study was undertaken at outpatient department of medicine in Rajah Muthiah Medical College and Hospital, Annamalai University, Chidambaram, Tamil Nadu, India. Forty hypertensive patients were randomly assigned to receive either slow breathing training for half an hour or as controls. For study group, 30 minutes of SB was practised through recorded auditory command. The breathing instruction consists of four seconds of inspiration and 6 seconds of expiration. Main outcome measured BP {Systolic (S) and Diastolic (D)} and EtCO2 . Paired sample t-test and independent sample t-test were the statistical tools used for inferential analysis. Results: The mean drop in SBP and DBP was 12.30±2.79 mmHg and 3.90±4.44 mmHg respectively in study group following training and it was statistically significant. The mean drop in SBP and DBP in controls was 1.05±3.34 and 0.30±2.10, respectively. There was significant reduction in EtCO2 following training in study group, the mean difference was 1.80±2.46. Between group analysis shows that, there was significantly greater reduction in SBP and DBP in study group following training but statistical significance was not achieved for EtCO2. Conclusion: Practice of slow breathing is effective in immediate reduction of systolic and diastolic BP. EtCO2 could play a role in reducing BP, but long-term study is warranted to better evaluate its role in BP reduction.

Background The etiology of interstitial cystitis (IC)/bladder pain syndrome (BPS) remains a mystery. Based on two patients, whose IC/BPS was relieved by resection of injured iliohypogastric (IH) and ilioinguinal (II) nerves, injured by endoscopic prostatectomy in the first patient and a stretch/traction injury in the second patient, a referred pain pathway is hypothesized that can be applied to patients with IC/BPS and previous abdominal wall surgery/injury. Methods The known neurophysiology of bladder function was reviewed as were the pathways for accepted referred pain syndromes. Results Perception of bladder filling occurs by impulses generated from stretch receptors in the bladder wall, traveling along visceral afferent fibers that enter the thoracolumbar spinal cord at T12, L1, and L2, the same location as the sympathetic outflow to the viscera and the same location as some of the visceral afferents from the bladder. The II and IH nerves originate from T12, L1, and sometimes L2 somatic, dorsal root ganglia. It is hypothesized that somatic afferent pain impulses, from the lower abdominal wall, are misinterpreted as visceral afferent impulses from the bladder, giving rise to the urinary frequency and urgency of IC/BPS. Resecting injured cutaneous afferents (II and IH) permitted long-term IC/BPS relief in the first patient for 59 months and in the second patient for 30 months. Neural inputs from the sacral visceral afferents and sacral somatic afferents did not appear to be involved in this referred pain pathway. Conclusion Nerve blocks of the T12 -L2 spinal nerves in patients with bladder pain who also have had abdominal wall surgery/injury may identify IC/BPS patients for whom resection of the II and IH nerves may prove beneficial in obtaining lasting IC/BPS relief.

Rapidly-adapting pulmonary stretch receptors (RAPSRs) provide the central nervous system with information regarding the rate of lung inflation, lung compliance and the sensation of dyspnea. Other than satisfying parameters of an adaptation index to constant pressure lung inflation for identification, no mathematical model has been ascribed to the stimulus-response relationship of lung volume-pressure to RAPSR activity. Herein, linear, power, polynomial and non-linear (four parameters logistic) models are tested for the best "goodness of fit" line of RAPSR activity to step-wise lung inflation to four times tidal volume and constant pressure inflation to 10, 20, 30 and 40 cm H2O of the lungs of guinea pigs and dogs. Goodness of fit was determined by evaluating coefficient of determination (R2) and visual inspection. The best "goodness of fit" is one of a non-linear symmetrical, stimulus-response function.

Background The aim of the present study was to investigate pulmonary stretch receptor activity (PSR) under different peak inspiratory pressures (PIPs) and inspiratory pressure waveforms during partial liquid (PLV) and gas ventilation (GV). Methods PSR instantaneous impulse frequency (PSRfimp) was recorded from single fibers in the vagal nerve during PLV and GV in young cats. PIPs were set at 1.2/1.8/2.2/2.7 kPa, and square and sinusoidal pressure waveforms were applied. Results PSRfimp at the start of inspiration increased with increasing PIPs, and was steeper and higher with square than with sinusoidal waveforms (p Conclusion As assessed by PSRfimp, increased PIPs do not expose the lungs to more stretching during PLV than during GV, with only minor differences between square and sinusoidal waveforms.

The study investigates the effects of 6 occlusion conditions on the mechanically induced cough reflex in 15 anesthetized (pentobarbital) spontaneously breathing cats (14♂, 1♀). Esophageal pressure and integrated EMG activities of inspiratory (I) diaphragm and expiratory (E) abdominal muscles were recorded and analyzed. Occlusions: inspiratory (Io), continual I (cIo), during I and active E (I+Eo) cough phase, during I and then E phase with short releasing of airflow before each phase (I-Eo), and E occlusion (Eo) had little influence on cough number. Only continual E occlusion (cEo) reduced the number of coughs by 19 % (to 81 %, p 0.05). Cough I esophageal pressure reached higher amplitudes under all conditions, but only Eo caused increased I diaphragm motor drive (p 0.05). Cough E efforts (abdominal motor drive and E amplitudes of esophageal pressure) increased during Eo, decreased during I+Eo (p 0.05), and did not change significantly under other conditions (p 0.05). All I blocks resulted in prolonged I cough characteristics (p 0.05) mainly cough I phase (incrementing part of the diaphragm activity). Shorter I phase occurred with cEo (p 0.05). Cough cycle time and active E phase (from the I maximum to the end of cough E motor drive) prolonged (p 0.05) during all occlusions (E phase duration statistically non-significantly for I+Eo). Airflow block during cough (occlusions) results in secondary changes in the cough response due to markedly altered function of cough central pattern generator and cough motor pattern produced. Cough compensatory effects during airflow resistances are more favorable compared to occlusions. Volume feedback represents significant factor of cough modulation under various pathological obstruction and/or restriction conditions of the respiratory system.

Many airway sensory units respond to both lung inflation and deflation. Whether those responses to opposite stimuli come from one sensor (one-sensor theory) or more than one sensor (multiple-sensor theory) is debatable. One-sensor theory is commonly presumed in the literature. This article proposes a multiple-sensor theory in which a sensory unit contains different sensors for sensing different forces. Two major types of mechanical sensors operate in the lung: inflation- and deflation-activated receptors (DARs). Inflation-activated sensors can be further divided into slowly adapting receptors (SARs) and rapidly adapting receptors (RARs). Many SAR and RAR units also respond to lung deflation because they contain DARs. Pure DARs, which respond to lung deflation only, are rare in large animals but are easily identified in small animals. Lung deflation-induced reflex effects previously attributed to RARs should be assigned to DARs (including pure DARs and DARs associated with SARs and RARs) if the multiple-sensor theory is accepted. Thus, based on the information, it is proposed that activation of DARs can attenuate lung deflation, shorten expiratory time, increase respiratory rate, evoke inspiration, and cause airway secretion and dyspnea.

The effect of volume-related feedback and output airflow resistance on the cough motor pattern was studied in 17 pentobarbital anesthetized spontaneously-breathing cats. Lung inflation during tracheobronchial cough was ventilator controlled and triggered by the diaphragm electromyographic (EMG) signal. Altered lung inflations during cough resulted in modified cough motor drive and temporal features of coughing. When tidal volume was delivered ( via the ventilator) there was a significant increase in the inspiratory and expiratory cough drive (esophageal pressures and EMG amplitudes), inspiratory phase duration (CT I ), total cough cycle duration, and the duration of all cough related EMGs (Tactive). When the cough volume was delivered ( via the ventilator) during the first half of inspiratory period (at CT I /2—early over inflation), there was a significant reduction in the inspiratory and expiratory EMG amplitude, peak inspiratory esophageal pressure, CT I , and the overlap between inspiratory and expiratory EMG activity. Additionally, there was significant increase in the interval between the maximum inspiratory and expiratory EMG activity and the active portion of the expiratory phase (CT E1 ). Control inflations coughs and control coughs with additional expiratory resistance had increased maximum expiratory esophageal pressure and prolonged CT E1 , the duration of cough abdominal activity, and Tactive. There was no significant difference in control coughing and/or control coughing when sham ventilation was employed. In conclusion, modified lung inflations during coughing and/or additional expiratory airflow resistance altered the spatio-temporal features of cough motor pattern via the volume related feedback mechanism similar to that in breathing.

Lung volume is modulated by sensory afferent feedback via vagal and spinal pathways. The purpose of this study was to systematically alter afferent feedback with and without a mechanical challenge (chest compression). We hypothesized that manipulation of afferent feedback by nebulization of lidocaine, extra-thoracic vagotomy, or lidocaine administration to the pleural space would produce differential effects on the motor pattern of breathing during chest compression in sodium pentobarbital anesthetized rats (N = 43). Our results suggest that: 1) pulmonary stretch receptors are not the sole contributor to breathing feedback in adult male and female rats; 2) of our manipulations, chest compression had the largest effect on early expiratory diaphragm activity ("yield"); 3) reduction of spinally-mediated afferent feedback modulates breathing patterns most likely via inhibition; and 4) breathing parameters demonstrate large sex differences. Compared to males, female animals had lower respiratory rates (RR), which were further depressed by vagotomy, while chest compression increased RR in males, and decreased yield in females without changing RR. Collectively, our results suggest that balance between tonic vagal inhibition and spinal afferent feedback maintains breathing characteristics, and that it is important to specifically evaluate sex differences when studying control of breathing.