Respiratory Period Research Articles

Increased stress associated with head-out plethysmography testing can exacerbate respiratory effects and lead to mortality in rats

IntroductionDSM421, a dihydroorotate dehydrogenase inhibitor, was in preclinical development as a potential treatment option for malaria. When tested in a core battery of safety pharmacology assays, DSM421 did not produce any effects at oral doses up to 750 mg/kg in an Irwin test in rats, but a respiratory study in rats using head-out plethysmography resulted in substantial changes in respiratory function as well as moribundity and mortality at that and lower doses. An investigation was performed to determine the source of this discrepancy. MethodsPotential testing errors, differences in types of plethysmography testing chambers, effects on stress indicators, and off-target activity were investigated. ResultsRespiratory changes and toxicity (resulting in euthanasia in extremis) were confirmed in a repeat, head-out plethysmography test, but the effects of DSM421 were much less severe overall when the rats were tested in whole-body chambers. Additionally, at the end of the 5-h post-dosing respiratory monitoring periods, levels of stress-related hormones (particularly corticosterone) were higher overall in the head-out, than in the whole-body, tested rats. Furthermore, DSM421 was found to produce changes in cardiovascular function in unrestrained rats, and it was shown to have off-target binding affinity at the adenosine A3 receptor (which is associated with bronchoconstriction). DiscussionThe generalized stress inherent to head-out plethysmography testing exacerbated the respiratory effects of DSM421 and was possibly compounded by DSM421's cardiovascular effects, thus artifactually resulting in moribundity and mortality in rats. Care should be taken when choosing whether to use head-out versus whole-body plethysmography chambers during respiratory function testing in animals.

The Effect of the Controlled Respiration Period on Physiological Phenomena

The Effect of the Controlled Respiration Period on Physiological Phenomena

Дослідження психофізіологічного стану студентів з урахуванням ступеня напруження регуляторних систем

The study revealed the relationship between the psychophysiological state of students and their adaptive abilities.The regulatory systems activity index (RSAI), proposed by RM Bayevsky, can be used as an integral measure of the functional stress of the autonomic nervous system. The increasing of RSAI level is associated with a number of changes in the structure of heart rate variability, such as increased activity of sympathetic nervous system, reduced respiratory periodicity, high index of centralization. It has been established that students with an unsatisfactory level of adaptation and depletion of regulatory mechanisms are characterized by a significantly higher level of personal anxiety, low stress stability, increased psychosomatic manifestations.

Alterations of the respiratory system in heart failure

The review discusses mechanisms for the development of the pathology of the respiratory system in patients with CHF, such as various types of periodic respiration, pulmonary hypertension due to the pathology of the left chambers of the heart, and remodeling of the respiratory musculature. The role of chemo- and baroreceptors of the carotid zone, as well as the hyperactivation of the respiratory muscle metaboreflex in the development of the pathology of the respiratory system, and the mediated exacerbation of CHF are discussed.

Low‐power contactless LC‐tank based respiratory sensor

In this Letter, a novel approach for contactless, low-cost and low-power respiratory sensing is presented, which is based on a commercial LC tank. This sensor is able to measure the variation of losses of induced eddy currents during one respiration period. The developed sensor system can be used in multiple different application fields where low-cost and low-power respiratory sensing is necessary. Examples for that can be infant or patient beds where vital parameters have to be monitored or in other fields where contactless presence check is desired. At first, the theory of operation and requirements for the respiratory sensing applications are explained which is followed by the system design and measurement results.

Flow kinematics in regions with flow recirculation inside nasal cavity

Flow kinematics was investigated in the regions located in the superior (region P) and inferior (region N) meatuses of the human nasal cavity where flow recirculation develops during the respiration period. The region P represents the posterior part of the ethmoidal sinus ostium, which several studies have reported as a frequent site for the development of nasal polyps. Region N located in the airflow passage in the inferior meatus, where polyp rarely form, was also investigated for comparison. Wall shear stress was found to be significantly reduced in both regions due to the development of flow separation, indicating a mechanical irritation of the epithelium by wall shear is likely to be quite suppressed. Even though the region P had a relatively smaller separation bubble, this region was found to have a longer particle residence time, which may increase the exposure time of foreign particles (e.g. allergens, pollen, and various pathogens) to the epithelium of the nasal airway.

Increased central cholinergic drive contributes to the apneas of serotonin-deficient rat pups during active sleep.

Infant rat pups lacking central nervous system (CNS) serotonin (5-hydroxytryptamine; 5-HT) have unstable breathing during prolonged periods of active sleep. Given that cholinergic neurons are drivers of active sleep and project to respiratory patterning regions in the brainstem, we hypothesized that 5-HT preserves respiratory stability in active sleep by dampening central cholinergic drive. We used whole-body plethysmography coupled with nuchal electromyography to monitor the breathing pattern of 2-wk-old tryptophan hydroxylase 2 (TPH2)+/+ and TPH2-deficient (TPH2-/-) pups in active sleep, before and after muscarinic blockade. For the group 1 experiment we injected methylatropine (Ap-M), a CNS-impermeant form of atropine, followed ~30 min later by an injection of atropine sulfate (Ap-S), the CNS-permeant form (both 1 mg/kg, 10 μl bolus iv); both injections occurred within an active sleep episode. We analyzed the effect of each drug on the coefficient of variation of the respiratory period (CV-P) during active sleep. For the group 2 experiment rats were cycled through several episodes of active and quiet sleep before administration of Ap-S (1 mg/kg, 200 μl ip) or vehicle. We assessed the effect of Ap-S on the apnea indices of both genotypes during quiet and active sleep. In group 1 Ap-S significantly reduced the CV-P of TPH2-/- pups (P = 0.03), an effect not observed in TPH2+/+ pups or following Ap-M. In group 2 the apnea index of TPH2-/- pups was significantly reduced following Ap-S injection (P = 0.04), whereas the apnea index of TPH2+/+ littermates was unaffected (P = 0.58). These findings suggest that central 5-HT reduces apnea and stabilizes breathing by reducing cholinergic signaling through muscarinic receptors. NEW & NOTEWORTHY Serotonin in the central nervous system (CNS) is necessary for maintaining the stability of breathing in the early postnatal period, particularly during active sleep. Here we show that the administration of atropine to the CNS selectively stabilizes the respiratory pattern of tryptophan hydroxylase 2-deficient rat pups and reduces their apneas. This suggests that CNS serotonin stabilizes breathing at least in part by reducing central cholinergic drive.

Evaluation of the structure and hemodynamics of internal jugular veins by ultrasound in normal population

Objective To investigate the structure and hemodyanmics characteristics of internal jugular veins (IJV) in normal population. Methods A total of 126 individuals for stroke screening and IJV ultrasound examination from Oct 2017 to May 2018 in our hospital were enrolled.The the level of IJV influx into innominate vein (J1), the level of superior thyroid vein influx into IJV (J2) and the level of the segment equal to from the bifurcation of common carotid artery to out of skull(J3) of IJV were evaluated by ultrasound. The parameters included the maximum diameters of the three segments during the smooth respiration period, cross section area (CSA), the maximum velocity (Vmax), mean flow volume (FVm) and the maximum pressure gradient (PGmax). The parameters of bilateral IJVs were compared. The effects of gender and age on these parameters were analyzed. Results The structures and hemodynamics parameters of left IJV were lower than those of right IJV (all P 0.05). With aging, the left/right ratio of Vmax and PGmax were decreased, especially at J1 segment (P<0.05). Conclusions Color Doppler flow imaging can evaluate the IJV structures and hemodynamics by assessing the diameter, CSA, Vmax, FVm and PGmax. Right IJV is the dominated outflow side in normal population. With aging, the drainage of left IJV is decreased. Key words: Ultrasonography; Jugular vein; Hemodynamics; Structure; Normal population

Характер кровоснабжения продолговатого мозга крыс при возникновении периодическом патологическом дыхании, вызванном оксибутиратом натрия

В острых опытах на наркотизированных самцах беспородных белых крыс изучали кровоснабжение ствола головного мозга в зоне дыхательного центра при моделировании периодического апнейстического дыхания с помощью оксибутирата натрия. При формировании периодического патологического дыхания в микрососудах ствола мозга возникают характерные периодические колебания кровотока и оксигенации нервной ткани, которые соответствуют дыхательным движениям. Кроме того, в этих условиях увеличивается кровенаполнение и величина венозного оттока крови от мозга. Полученные данные позволяют предположить, что характерные колебания кровоснабжения мозга в ритме дыхательных движений появляются не только в стволе мозга, но и в других отделах. Они, вероятно, связаны с пульсациями венозного оттока вследствие присасывающего влияния грудной полости во время инспирации. The model of periodic apneustic respiration provoked by sodium hydroxybutyrate was used in acute experiments on anaesthetized mongrel male albino rats to examine the blood supply to the region of respiratory center in the brain stem. The development of periodic pathological respiration was associated with specific periodic oscillations of 1) blood flow in the brain stem microvasculature and 2) oxygenation of the nervous tissue following the respiration rhythm. Under these conditions, both blood supply to and venous outflow from the brain were augmented. The study suggested that the characteristic oscillations of blood supply to the brain at the respiration rhythm emerge not only in the brain stem but also in other cerebral regions. Probably, they are caused by oscillations of venous outflow induced by the suction effect of the chest cavity during inspiration.

Paced Breathing Increases the Redundancy of Cardiorespiratory Control in Healthy Individuals and Chronic Heart Failure Patients.

Synergy and redundancy are concepts that suggest, respectively, adaptability and fault tolerance of systems with complex behavior. This study computes redundancy/synergy in bivariate systems formed by a target X and a driver Y according to the predictive information decomposition approach and partial information decomposition framework based on the minimal mutual information principle. The two approaches assess the redundancy/synergy of past of X and Y in reducing the uncertainty of the current state of X. The methods were applied to evaluate the interactions between heart and respiration in healthy young subjects (n = 19) during controlled breathing at 10, 15 and 20 breaths/minute and in two groups of chronic heart failure patients during paced respiration at 6 (n = 9) and 15 (n = 20) breaths/minutes from spontaneous beat-to-beat fluctuations of heart period and respiratory signal. Both methods suggested that slowing respiratory rate below the spontaneous frequency increases redundancy of cardiorespiratory control in both healthy and pathological groups, thus possibly improving fault tolerance of the cardiorespiratory control. The two methods provide markers complementary to respiratory sinus arrhythmia and the strength of the linear coupling between heart period variability and respiration in describing the physiology of the cardiorespiratory reflex suitable to be exploited in various pathophysiological settings.

Effects of Restrictive Fluid Management in Transient Tachypnea in Neonates

Background: The transient tachypnea is a common respiratory problem in the neonate. One of the significant issues in pathophysiology of this disorder is the delayed reabsorption of the fluid by the neonate’s lungs and the effusion of fluid in the lungs. The purpose of this study is to evaluate the effects of restrictive fluid management in transient tachypnea of the neonate. Methods: The present study was conducted on the neonates with the gestational age ≥ 34 weeks suffering from transient tachypnea during the first 6 h after birth. The amounts of total fluid in experimental and control groups were 50, 65 mL/kg and 65, 80 mL /kg for term and preterm neonates, respectively. In each group, a daily amount of 20 mL/kg fluid was added until 150 and 170 mL/kg for term and preterm newborns. Results: This study was carried out on 70 neonates, including 34 cases and 36 controls. The mean of hospitalization period in the experimental group was less than that of the control group. The mean period of respiratory support in the experimental group was less than that in the control group. Conclusion: The results of the present study revealed that the restrictive fluid management in the neonates with transient tachypnea might decrease the hospitalization period and the respiratory support period. Furthermore, it is a safe and effective method in treating transient tachypnea in neonates.

Effects of ethylene and 1-MCP on quality maintenance of fresh cut celery

Ethylene is accepted to be a key player in the regulation of climacteric fruit ripening and senescence of leafy vegetables. In contrast, there is still disparity in the literature on the role it may have on quality deterioration of edible petioles. In this work, we evaluated the influence of the ethylene generator 2-chloroethylphosphonic acid (Ethephon) and the ethylene action inhibitor 1-methylcyclopropene (1-MCP) on quality maintenance of fresh cut celery. Commercially mature stalks from self-blanching celery cv. Golden Clause were cut into 2 cm-long slices. Samples from the apical and basal petiole zones were segregated and treated with 2000 mg L−1 2-chloroethylphosphonic acid or with 1 μL L−1 1-MCP. Corresponding slices without any treatment were used as control. Samples were packed and stored for 0, 6, 13 and 20 d at 4 °C and during this period celery visual deterioration (VD), respiration, weight loss and aerobic mesophilic bacteria, yeasts and molds counts were determined. Carotenoids, chlorophylls, phenolics, ascorbic acid, polyphenol oxidase (PPO), sugars, acidity, cell wall content and consumer acceptability were also evaluated. Ethylene had no major effects on weight loss, PPO, phenolic, sugars, acidity, and ascorbic acid. Instead, it increased respiration and accelerated chlorophyll degradation and surface yellowing. These changes were delayed in 1-MCP treated celery, which also maintained lower mesophilic bacteria and yeast counts, showed lower incidence of soft rots. 1-MCP treated celery received higher consumer acceptability scores. The effects were more marked on the samples obtained from the apical region of the petioles. Overall, results reassess the role of ethylene on celery petiole metabolism and indicate that 1-MCP treatments may be useful to supplement the benefits of refrigeration and extend the shelf life of fresh cut self-blanching celery.

Investigation of flow characteristics in the maxillary sinus where polypoid changes develop

Flow behavior in the maxillary sinus where polypoid changes develop was investigated using computational fluid dynamics. A nasal cavity model was constructed, after performing a virtual polypectomy based on computed tomography images of a patient, using a computer-aided design software to artificially remove polypoid changes inside the maxillary sinus. Local flow characteristics in the maxillary sinus were examined for one full respiration period.The results showed that the epithelial surfaces where polypoid changes occur are located in the lower part of the maxillary sinus which contains a protruding zone of the sinus and are characterized by stagnation of air during the entire respiration period. Due to the geometric characteristics, a very slow recirculating motion was found to occur in the bulging area for approximately half of the respiration period as a result of interaction with a larger-scale, counter-rotating vortex filling the middle of the maxillary sinus. With a much smaller velocity inside the maxillary sinus compared to that typically found in the airway passage through the middle meatus, both wall shear and pressure changes were found to be vanishingly small along the epithelial surface of the maxillary sinus where polypoid changes were found.

Oxygen Exchange and Primary Production of Zostera japonica Ascherson et Graebner 1907 Community in the Golubinyi Bay (Sea of Japan)

The net primary production per daylight period (Pn, dl) and dark respiration per day (Rd) of the eelgrass Zostera japonica community were measured in situ by the continuous-flow-system method in the Golubinyi Bay (Sea of Japan) in May–June 2008–2012; the obtained values were Pn = 3.37 g О2/(m2 dl) and Rd = 7.21 g О2/(m2 d). The photosynthesis rate of Z. japonica depended on the intensity of photosynthetically active radiation (PAR) and salinity. The gross primary production (Pg) of the Z. japonica community was 6.98 g О2/(m2 d) or 2.62 g С/(m2 d) at the salinity of 34–17‰. With reduction of water salinity to 8–1‰, the Pg of the Z. japonica community decreased to 2.17 g O2/(m2 d) or 0.81 g C/(m2 d), because of a lower rate of photosynthesis in plants. The primary production of Z. japonica was 6.10 g O2/(m2 d) or 87.4% of the gross production of the community. The ratio of gross production to dark respiration (Pg/R) was approximately 1.0, indicating the balance of autotrophic and heterotrophic processes in the community.

Cine 4DCT imaging artifacts: Quantification and correlations with scanning parameters and target kinetics

To study temporal resolved computed tomography imaging (4-Dimensional Computed Tomography: 4DCT) artifacts correlations with scanning parameters and target kinetics and to assess uncertainty introduced by 4DCT in radiotherapy treatment planning.In this work we classified 4DCT artifacts as finite gantry rotation speed related (FGS) and finite sampling frequency related (FSF). We studied FGS artifacts using a respiratory phantom and FSF artifacts using a Monte Carlo simulation of acquisition timing.From our analysis FGS localization error is comparable with image resolution determined by voxel dimensions. Remaining FGS artifacts are correlated with gantry rotation time (Trot), target velocity (v) and their interaction.FSF artifacts occurrence is correlated with sampling ratio (SR), i.e. the ratio of patient respiratory period (Tresp) and sampling time (Ts).In the studied velocity range (0–2 cm/s), using a Trot of 0,5s and a SR higher than 15, FGS and FSF artifacts became comparable with other sources of uncertainty.Our considerations are valid for “ideal” breathing pattern only. When variations from periodical breathing, high target velocity (more than 2 cm/s) or high peak to peak amplitude (more than 2 cm) are present, patient specific images artifacts analysis is recommended.

Instrumentation for respiratory flow estimation using tracheal sounds analysis: Design and evaluation in measurements of respiratory cycle periods and airflow amplitude

The increase in the incidence of respiratory diseases resulted in an increased interest in the improvement of the instruments used in research and diagnosis of respiratory dysfunction. We developed a non-invasive instrument able to estimate ventilation parameters by means of tracheal sounds analysis (TSA). The development of the hardware and software used in the instrument is described, as well as initial in vivo results obtained in a normal subjects. These tests showed that the TSA was able to provide adequate airflow estimative. Moreover, it was found that accurate respiratory periods can be obtained from tracheal sounds. These results were in close agreement with the physiology, confirming the high scientific and clinical potential of this system.

IMRT dose verification considering passing rate and respiratory motion.

The aim of the present study was to investigate the association between the dynamic intensity-modulated radiation therapy planned γ analysis passing rate and respiratory amplitude (A) and period (T) for different tumor volumes. A total of 30 patients with malignant lung tumors were divided into three groups: A; B; and C. The average tumor volumes (V) in the A, B and C groups were 635, 402 and 213 cm3, respectively. The simulated A values were set at 0, 5, 10, 15, 20 and 25 mm. The T values were set at 4, 5 and 6 sec. The γ analysis passing rate was calculated under different conditions (dose difference, 3%; distance difference, 3 mm). Compared with the γ analysis passing rate in the A group (A=0, static; T=4, 5, 6 sec), the γ analysis passing rate deviation (A=5 mm) was <3.3%. However, this difference was not statistically significant (P>0.05). With a gradual increase in A value, the passing rate decreased. The deviation between the 3 groups was <2.5% at the same A value (T=4, 5 and 6 sec). A descending trend of passing rate with increased A value was revealed. At the same A and T values, the passing rate decreased with decreased tumor volume. At the same tumor volume, the passing rate decreased when the A value increased. The respiratory cycle was not demonstrated to be associated with the passing rate. Overall, these results suggest that the A value should be controlled in clinical radiotherapy.

Optimization of training periods for the estimation model of three-dimensional target positions using an external respiratory surrogate

BackgroundDuring therapeutic beam irradiation, an unvisualized three-dimensional (3D) target position should be estimated using an external surrogate with an estimation model. Training periods for the developed model with no additional imaging during beam irradiation were optimized using clinical data.MethodsDual-source 4D-CBCT projection data for 20 lung cancer patients were used for validation. Each patient underwent one to three scans. The actual target positions of each scan were equally divided into two equal parts: one for the modeling and the other for the validating session. A quadratic target position estimation equation was constructed during the modeling session. Various training periods for the session—i.e., modeling periods (TM)—were employed: TM ∈ {5,10,15,25,35} [s]. First, the equation was used to estimate target positions in the validating session of the same scan (intra-scan estimations). Second, the equation was then used to estimate target positions in the validating session of another temporally different scan (inter-scan estimations). The baseline drift of the surrogate and target between scans was corrected. Various training periods for the baseline drift correction—i.e., correction periods (TCs)—were employed: TC ∈ {5,10,15; TC ≤ TM} [s]. Evaluations were conducted with and without the correction. The difference between the actual and estimated target positions was evaluated by the root-mean-square error (RMSE).ResultsThe range of mean respiratory period and 3D motion amplitude of the target was 2.4–13.0 s and 2.8–34.2 mm, respectively. On intra-scan estimation, the median 3D RMSE was within 1.5–2.1 mm, supported by previous studies. On inter-scan estimation, median elapsed time between scans was 10.1 min. All TMs exhibited 75th percentile 3D RMSEs of 5.0–6.4 mm due to baseline drift of the surrogate and the target. After the correction, those for each TMs fell by 1.4–2.3 mm. The median 3D RMSE for both the 10-s TM and the TC period was 2.4 mm, which plateaued when the two training periods exceeded 10 s.ConclusionsA widely-applicable estimation model for the 3D target positions during beam irradiation was developed. The optimal TM and TC for the model were both 10 s, to allow for more than one respiratory cycle.Trial registrationUMIN000014825. Registered: 11 August 2014.

Muscarinic blockade stabilizes the breathing pattern of serotonin‐deficient rat pups during active sleep

Infant rats deficient in tryptophan hydroxylase 2 (TPH2−/−) and hence lacking central serotonin (5‐hydroxytryptamine; 5‐HT) display abnormally destabilized breathing during active sleep; their breathing pattern is punctuated with periods of apnea and tachypnea. Given that acetylcholine is a key driver of active sleep, as well as the fact that muscarinic receptors are abundantly expressed within key respiratory patterning regions, we hypothesized that increased central muscarinic drive contributes to the unstable breathing pattern of infant TPH2−/− rats during active sleep. To test this hypothesis, we conducted two separate experiments using whole‐body plethysmography coupled with nuchal EMG to monitor the breathing pattern of 2‐week‐old TPH2−/− and WT pups during active sleep. Experiment 1: following ~1 hr settling period to allow for the appearance of active sleep, we injected atropine methyl nitrate (Ap‐M), a CNS‐impermeant form of atropine, followed ~30 min later by an injection of atropine sulfate (Ap‐S), a CNS‐permeant form (both 1mg/kg, 10 ul bolus i.v.) (n= 8 and 10 TPH2−/− for Ap‐M and Ap‐S, respectively; n=8 WT for both drugs). Each drug was injected during a period of active sleep. For most animals, arousal did not occur and the effect of the drugs on the co‐efficient of variation in the respiratory period (CV‐P%) could be determined within one episode of active sleep. If arousal occurred, CV‐P% prior to injection was compared to CV‐P% in the next episode of active sleep. Experiment 2: the breathing pattern of TPH2−/− pups was monitored over 2 hrs before and after the administration of Ap‐S (1 mg/kg, 200 ul bolus i.p; n=17) or vehicle (saline; n=16). Tachypnea and apnea indices (# events/hr) were calculated for the active sleep episodes before and after Ap‐S. Administration of Ap‐M increased heart rate (~30–50 beats/min) and decreased heart rate variability for the duration of the experiment. In WT pups, CV‐P% tended to increase after i.v. administration of Ap‐M, but was not significantly changed following Ap‐S. In contrast, the CV‐P% of TPH2−/− pups was significantly increased after Ap‐M (p&lt;0.01) and significantly reduced following Ap‐S (p=0.01). Ap‐S significantly reduced the tachypnea index of TPH2−/− pups relative to TPH2−/− pups given vehicle alone (p=0.04), but had no significant effect on apnea index. The reduced CV‐P% of TPH2−/− pups after Ap‐S relative to values after Ap‐M suggest that muscarinic blockade in the CNS by Ap‐S reverses the destabilizing effect of 5‐HT deficiency on the respiratory pattern. This occurs in spite of a destabilizing peripheral effect of Ap‐M on the breathing pattern. These data also suggest that during active sleep, 5‐HT signaling helps stabilize the breathing pattern of infant rats mainly by inhibiting muscarinic drive to patterning neurons promoting tachypnea.Support or Funding InformationFunding for this research was provided by an American Heart Association Scientist Development Grant (14SDG18560022; PI: KJC) and a Ruth L. Kirschstein National Research Service Award (NRSA) Individual Predoctoral Fellowship (F31) to JLM.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Phase synchronization as a flexible definition of the respiratory pattern: Application to pontine‐dependent control of the respiratory pattern

A distinct pattern of inspiratory, post‐inspiratory and expiratory activities that are expressed in respiratory‐modulated neurons and motor outputs during stationary breathing are the foundation of most contemporary models for respiratory rhythm generation and pattern formation. Models and experiments show that impaired synaptic inhibition in the respiratory circuitry of the brainstem is associated with neurogenic breathing disorders in Rett syndrome (inspiratory efforts against a closed glottis) or with paradoxical vocal cord movement (glottal closure during inspiration). Previously, we reported that the pontine Kölliker‐Fuse nuclei (KFn) couple the spinal and cranial motor patterns and control respiratory pattern variability. Here, we test the hypothesis that the KFn is critical for expression of the phase relationships among respiratory motor activities. In arterially‐perfused brainstem preparations (n=7), we recorded respiratory activity from the hypoglossal, cervical vagal, phrenic and iliohypogastric nerves before and after bilateral bicuculline (a GABA(A)R antagonist, 50nl, 10mM) microinjections in the KFn. Disinhibition of KFn increased the variability of the respiratory rhythm (coefficient of variation (CV) of cycle duration (TTOT before, 0.10 ± 0.01 versus after bicuculline 0.50 ± 0.26, p&lt;0.01). The increase in variability was associated with unpredictable timing of phase durations and transitions. Standard metrics such as TTOT failed to quantitatively describe the complexity in the changes of the respiratory motor pattern. Here, we introduce a quantitative definition of the respiratory motor pattern based on the phase synchronization of respiratory motor outputs or its underlying neuronal activities. Power spectral analysis revealed that the respiratory motor activities had a periodicity indicating that a coherent respiratory‐pattern persisted. Quantifying phase synchronization of respiratory motor outputs revealed a significant reduction in coupling strengths, without a change in their relative phase relationships (mean relative phase at baseline, 1.16 ± 0.07 rad versus after disinhibition, 1.17 ± 0.05 rad; and phase coherence at baseline, 0.87 ± 0.01 versus after disinhibition, 0.31 ± 0.03, p=3.68×10−4). Our data further support the concept that respiratory pattern formation requires reciprocal interaction between pontine and medullary respiratory groups. Focal pontine disinhibition resulted in reduced coupling strength between ponto‐medullary synaptic interactions that consequently disrupted the motor pattern, while the undisturbed medullary aspects are able to uphold the periodicity of respiration. Taken together, our results illustrate that medullary respiratory rhythm generating circuit require the pons to convert its periodicity into a viable and vital respiratory motor pattern.Support or Funding InformationSupported by a grant from the Australian Research Council.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.