Pharyngeal Water Research Articles

Pharyngoesophageal and cardiorespiratory interactions: potential implications for premature infants at risk of clinically significant cardiorespiratory events.

The aims of this study were to 1) examine pharyngoesophageal and cardiorespiratory responses to provoking pharyngeal stimuli, and 2) to determine potential contributory factors impacting heart rate (HR) changes to provide insight into cardiorespiratory events occurring in preterm infants. Forty-eight neonates (19 females and 29 males, born at 27.7 ± 0.5 wk; mean ± SE) pending discharge on full oral feeds were studied at 38.7 ± 0.2 wk postmenstrual age using concurrent pharyngoesophageal manometry, electrocardiography, respiratory inductance plethysmography, and nasal airflow thermistor. Pharyngoesophageal and cardiorespiratory responses (prevalence, latency, and duration) were quantified upon abrupt pharyngeal water stimuli (0.1, 0.3, and 0.5 ml in triplicate). Mixed linear models and generalized estimating equations were used for comparisons between HR changes. Contributory factors included stimulus characteristics and subject characteristics. Of 338 pharyngeal stimuli administered, HR increased in 23 (7%), decreased in 108 (32%), and remained stable in 207 (61%) neonates. HR decrease resulted in repetitive swallowing, increased respiratory-rhythm disturbance, and decreased esophageal propagation rates (all, P < 0.05). HR responses were related to stimulus volume, stimulus flow rate, and extreme prematurity (all, P < 0.05). In preterm infants, HR remains stable in a majority of pharyngeal provocations. HR decrease, due to pharyngeal stimulation, is related to aberrant pharyngoesophageal motility and respiratory dysregulation and is magnified by prematurity. We infer that the observed aberrant responses across digestive, respiratory, and cardiovascular systems are related to maladaptive maturation of the parasympathetic nervous system. These aberrant responses may provide diagnostic clues for risk stratification of infants with troublesome cardiorespiratory events and swallowing difficulty. NEW & NOTEWORTHY Cardiorespiratory rhythms concurrent with pharyngeal, upper esophageal sphincter, and esophageal body responses were examined upon pharyngeal provocation in preterm-born infants who were studied at full-term maturation. Decreased heart rate (HR) was associated with extreme preterm birth and stimulus flow/volume. With HR decrease responses, aerodigestive reflex abnormalities were present, characterized by prolonged respiratory rhythm disturbance, repetitive multiple swallowing, and poor esophageal propagation. Promoting esophageal peristalsis may be a potential therapeutic target.

Behavioural and neurophysiological disruption of corticobulbar motor systems and their effects on sequential pharyngeal swallowing

Primary motor networks are known to be involved in the control of voluntary oral movements as well as the modulation of pharyngeal movements during experimentally controlled single swallows performed on command. The role of these networks in the more typical task of sequential swallowing remains unexplored. This study evaluated the hypothesis that experimental disruption of motor cortical activation would reduce the rate and regularity of repeatedly performed volitional or volitionally initiated motor tasks controlled by corticospinal (finger tapping) and corticobulbar (eyebrow movement, jaw opening, volitional sequential swallowing) motor systems, but would not influence a more reflexive corticobulbar task (reflexive sequential swallowing to pharyngeal water infusion). This premise was investigated in 24 healthy participants using two techniques: a dual task paradigm and a transcranial magnetic stimulation paradigm. Disruption effects were quantified by changes in rate and regularity of performance for each tested motor task. In summary, volitional motor tasks controlled by corticospinal motor networks (finger tapping) are more susceptible to behavioural and neurophysiological disruption than tasks controlled by cortiobulbar motor networks containing a reflexive component (both volitional and experimentally initiated consecutive swallowing). Purely volitional motor tasks controlled by the corticobulbar motor system (eyebrow raising or jaw opening) were affected in similar ways as the volitional corticospinal motor tasks. In summary, tasks involving sequential pharyngeal swallowing - whether volitionally or experimentally initiated - are largely robust against disruption of primary cortical motor networks, supporting a key role of medullary CPGs in the motor control of sequential pharyngeal swallowing.

Effects of pharyngeal water stimulation on swallowing behaviors in healthy humans

The aims of the present study were to determine whether the interval between swallows and the electromyographic (EMG) burst patterns of the suprahyoid muscles is affected by peripheral inputs during swallowing. Eighteen normal adults were asked to perform repetitive voluntary swallowing as quickly as possible, and three variables of swallowing were measured and evaluated, i.e., the swallowing intervals and the time interval between the onset and peak (rising time) and between the peak and offset (falling time) of the suprahyoid EMG burst. During recording, pharyngeal fluid infusion was applied with distilled water or 0.3 M NaCl solution at a very slow infusion rate (0.2 mL/min). The former and latter were used to activate and inhibit the excitation of water-sensitive receptors in the pharynx, respectively. The swallowing interval was significantly shorter during infusion of water than during infusion of NaCl solution. The rising time was also significantly shorter during infusion of water than during infusion of NaCl solution. There was a linear positive correlation between these values and facilitatory effects: the longer either the swallowing interval or rising time with infusion of 0.3 M NaCl solution, the stronger the facilitation of swallowing by the activation of water receptors. Facilitatory effects on the swallowing interval and rising time showed a linear correlation. It is suggested that weak liquid stimulation changed sensory inputs into the swallowing center and synchronously modulated the swallowing interval and time interval between the onset and peak of the EMG burst.

Relationship of pharyngeal water content and jugular volume with severity of obstructive sleep apnea in renal failure

In patients with end-stage renal disease (ESRD), fluid overload may contribute to their high prevalence of obstructive sleep apnea (OSA) by increasing the amount of fluid displaced from the legs into the neck overnight, and possibly compressing the upper airway (UA). Indeed, in ESRD patients, the amount of overnight rostral fluid displacement from the legs is related to the frequency of apneas and hypopneas per hour of sleep (apnea-hypopnea index, AHI). We, therefore, hypothesized that in ESRD patients, the greater the UA-mucosal water content (UA-MWC) and internal jugular vein volume (IJVVol), the higher the AHI. We studied 20 patients with ESRD on thrice weekly hemodialysis who had undergone diagnostic polysomnography (age 41.0 ± 12.3 years, with a body mass index (BMI) of 25.8 ± 6.3 kg/m(2) and an AHI of 20.2 ± 26.8). The leg fluid volume (LFV) was measured by bioelectric impedance. The IJVVol and MWC were measured by UA magnetic resonance imaging (MRI). The only significant independent correlates of the AHI were IJVVol (r = 0.801, P < 0.0001) and UA-MWC (r = 0.720, P = 0.0005) which together explained 72% of its variability. These data suggest that fluid overload via increased IJVVol, and UA-MWC, contributes to the pathogenesis of OSA in patients with ESRD. These findings help us to explain the high prevalence of OSA in ESRD patients, and attenuation of OSA in association with nocturnal dialysis. They also suggest the need for randomized trials to determine whether more aggressive fluid removal in ESRD patients will alleviate OSA.

Pharyngoglottal Closure Reflex: Characterization in Healthy Young, Elderly and Dysphagic Patients with Predeglutitive Aspiration

Background: Mechanism(s) of aspiration, a common complication of oropharyngeal dysphagia, is not completely elucidated. Since the pharyngoglottal closure reflex induces vocal cord adduction in healthy young humans, it may help prevent aspiration during premature spill of oral content. Objective: The objective of this study was to characterize this reflex in normal young and elderly humans and dysphagic patients with predeglutitive aspiration; a potential group for developing abnormalities of this reflex. Methods: We used a concurrent video endoscopic and manometric technique for recording of the vocal cords’ response to pharyngeal water stimulation. We first studied 9 young (26 ± 2 years) and 9 elderly (77 ± 14 years) healthy volunteers to characterize and determine the effect of aging on the pharyngoglottal closure reflex. Subsequently, we studied 8 patients (65 ± 16 years) with predeglutitive aspiration and 7 age-matched controls to characterize this reflex among patients with compromised airway safety during swallowing. Results: The threshold volume of water for triggering both glottal closure and reflexive pharyngeal swallow in the elderly volunteers for rapid pulse injection was significantly larger than that for the young (p < 0.05). Neither glottal closure reflex nor pharyngeal reflexive swallow could be induced in any of the dysphagic patients with volumes of injected water as large as 1 ml. In contrast, in all age-matched controls, both the pharyngoglottal reflex and reflexive pharyngeal swallow were stimulated with threshold volumes of 0.3 ± 0.07 and 0.6 ± 0.05 ml, respectively. Conclusions: Pharyngeal stimulation by water induces vocal cord adduction in humans; the pharyngoglottal closure reflex. Although preserved, a significantly larger volume of water is required to stimulate this reflex by rapid pulse injection in the elderly, suggesting some deterioration in this age group. The pharyngoglottal closure reflex induced by rapid pulse injection is absent in dysphagic patients with predeglutitive aspiration, suggesting its contribution to airway protection against aspiration.

Deterioration of the pharyngo-UES contractile reflex in the elderly.

Deterioration of aerodigestive tract reflexes such as the esophagoglottal and pharyngoglottal closure reflexes and pharyngeal swallow has been documented in the elderly. However, the effect of aging on the contractile response of the upper esophageal sphincter (UES) to pharyngeal water stimulation has not been studied. The aim of this study was to characterize the pharyngo-UES reflex in the healthy elderly. We studied nine healthy elderly (77 +/- 1 y [SD]; four men, five women) and nine healthy young volunteers (26 +/- 2 y [SD]; four men, five women). AUES sleeve sensor was used to measure the pressure. We tested pharyngeal stimulation induced by rapid pulse and slow continuous injection of water. The volume of water required to stimulate the pharyngo-UES contractile reflex by rapid pulse injection in the elderly (0.5 +/- 34 0.1 mL) was significantly higher than that in the young (0.1 +/- 0.02 mL) (P < .05). In contrast to young subjects, there was no pressure increase in resting UES pressure observed in the elderly for continuous pharyngeal water infusion. In both young and elderly, the threshold volume for the pharyngo-UES contractile reflex was significantly lower than that for pharyngeal swallows. The pharyngo-UES contractile reflex deteriorates with aging. This deterioration is primarily due to abnormalities of the afferent limb of the reflex.

Disruption of primary and secondary esophageal peristalsis by afferent stimulation.

Recent studies have shown that afferent signals originating from the pharynx inhibit progression of primary esophageal peristalsis. Our aim was to further elucidate the effect of esophageal and pharyngeal afferent stimulation on primary and secondary esophageal peristalsis. We studied the effect of esophageal air distension and pharyngeal water stimulation on progression of primary and secondary peristalsis in nine healthy volunteers aged 27 +/- 2 yr (4 men, 5 women). At a threshold volume, rapid injection of water into the pharynx, directed posteriorly, resulted in complete halt of the progressing secondary and primary esophageal peristalses in both the proximal and distal esophagus. The threshold volume of injected water for inducing inhibition was similar for secondary (0.6 +/- 0.2 ml) and primary (0.5 +/- 0.1 ml) esophageal peristalsis. Progression of primary peristalsis induced by a dry swallow and secondary peristalsis induced by intraesophageal air distension were completely inhibited by intraesophageal injection of 15 +/- 2 ml of air in 70% and 75% of the trials, respectively. We conclude that afferent signals induced by esophageal air distension and pharyngeal water stimulation inhibit propagation of both primary and secondary esophageal peristalsis, suggesting a shared neural control mechanism for these types of peristalsis.

Effect of pharyngeal stimulation on the motor function of the esophagus and its sphincters.

Sensory impulses from the pharynx induce contraction of the upper esophageal sphincter (UES), relaxation of the lower esophageal sphincter (LES), and inhibition of peristalsis. To determine 1) the magnitude of UES contractile response to threshold volume of fluid that induces LES relaxation and 2) the effect of rapid pharyngeal air stimulation on LES resting pressure and its concurrent influence on the UES and progression of esophageal peristalsis. Eleven healthy volunteers (age, 31 +/- 2 y) were studied by concurrent UES, esophagealbody, and LES manometry. At a threshold volume of 0.3 +/- 0.05 mL, injections of water into the pharynx directed posteriorly, resulted in complete LES relaxation. Duration of these relaxations averaged 19 +/- 1 seconds. In 10 of 11 subjects, these relaxations were accompanied by a simultaneous increase in UES resting tone that averaged 142% +/- 27% above preinjection values. Pharyngeal stimulation by rapid air injection resulted in complete LES relaxation in 8 of the 11 subjects (threshold volume, 14 +/- 6 mL). Five of 8 developed a concurrent mild increase in resting UES pressure (17% +/- 6% above preinjection values) (P < .05). Pharyngeal water injection inhibited the progression of the peristaltic pressure wave at all tested sites and in all subjects, but pharyngeal air injection in only 2 of the 11 studied subjects. The inhibitory effect of pharyngeal water injection on LES resting pressure is accompanied by a substantial contractile effect on the UES. Although stimulation of the pharynx by rapid air injection may induce LES relaxation, its inhibitory effect on esophageal peristalsis and stimulatory effect on UES pressure are negligible compared with that of water injection.

Pharyngoglottal closure reflex: identification and characterization in a feline model.

Earlier studies in humans have shown that pharyngeal stimulation by water at a threshold volume induces a brief vocal cord adduction, i. e., pharyngoglottal closure reflex. The present study was undertaken to 1) develop a suitable animal model for physiological studies of this reflex and 2) delineate its neural pathway and effector organs. Studies were done in cats by concurrent videoendoscopy and manometry followed by electromyographic studies. At a threshold volume (0.3 +/- 0.06 ml), injection of water into the pharynx resulted in a brief closure of the vocal folds, closing the introitus to the trachea. Duration of this closure averaged 1.1 +/- 0.1 s. Bilateral transection of the glossopharyngeal nerve completely abolished this reflex but not swallows induced by pharyngeal water stimulation. The pharyngoglottal closure reflex is present in the cats. The glossopharyngeal nerve is the afferent pathway of this reflex, and the interarytenoid and lateral cricoarytenoid muscles are among its target organs.

Characterization of the pharyngo-UES contractile reflex in humans.

Preliminary human studies suggest the presence of an upper esophageal sphincter (UES) contractile reflex triggered by pharyngeal water stimulation. The purposes of this study were to further characterize this reflex and determine the threshold volume for its activation. We studied 10 healthy young volunteers by manometric technique before and after topical pharyngeal anesthesia. UES pressure responses to various volumes and temperatures of water injected into the pharynx were elucidated. At a threshold volume, rapid-pulse and slow continuous pharyngeal water injection resulted in significant augmentation of UES pressure in all volunteers. Threshold volume for inducing UES contraction averaged 0.1 +/- 0.01 ml for rapid-pulse injection and was significantly smaller than that for slow continuous injection (1.0 +/- 0.2 ml). UES pressure increase duration averaged 16 +/- 4 s. Augmentation of UES resting tone by injection of water with three different temperatures was similar. This augmentation was abolished after topical anesthesia. Conclusions were that stimulation of the human pharynx by injection of minute amounts of water results in a significant increase in resting UES pressure: the pharyngo-UES contractile reflex. The magnitude of pressure increase due to activation of this reflex is not volume or temperature dependent. Loss of pharyngeal sensation abolishes this reflex.

Frequency of gastroesophageal reflux events induced by pharyngeal water stimulation in young and elderly subjects.

Earlier studies have shown that isolated complete lower esophageal sphincter (LES) relaxation occurs as a result of pharyngeal water stimulation. Association of these relaxations with gastroesophageal reflux has not been studied systematically. Our aim was to determine this association in young and elderly subjects during precibal and postprandial periods. We studied 8 young subjects and 10 elderly subjects for 1 h before and 2 h after a 1,000-cal meal. In both groups, during the precibal period, negligible LES relaxation induced by pharyngeal water stimulation resulted in gastroesophageal reflux. In the postprandial period, gastroesophageal reflux events occurred after 16% of pharyngeal water injections in young subjects and after 44% in elderly subjects (P < 0.05). Intraabdominal length of the LES in elderly subjects was significantly shorter compared with younger subjects (P < 0.05). We conclude that gastroesophageal reflux events induced by pharyngeal water stimulation in the postprandial period are significantly increased compared with those of the precibal period and are significantly more prevalent in the elderly compared with the young. These differences seem to be associated with a significantly shorter intra-abdominal segment of the LES in the elderly.

Effect of pharyngeal water stimulation on esophageal peristalsis and bolus transport.

Sensory stimuli originating from the pharynx inhibit esophageal peristalsis induced by a dry swallow. Our aims were to determine the effect of these stimuli on esophageal bolus transport and esophageal peristalsis induced by swallowing different volumes of liquid and semisolid boluses. We studied nine healthy volunteers age 35 +/- 4 yr in the supine position by intraluminal esophageal manometry as well as concurrent videofluoroscopy and manometry. In all subjects progression of peristalsis induced by swallowing of different volumes of water and mashed potato boluses was inhibited at all sites by pharyngeal water injection. Threshold volume for inhibition of the peristalsis induced by swallows of 5 and 10 ml of water was similar but significantly higher compared with dry swallows (P < 0.05). Pharyngeal water injection invariably halted transit of the barium boluses through the esophagus. Sensory impulses originating from the pharynx 1) inhibit esophageal bolus transit and 2) are capable of overcoming the facilitating effect of a liquid bolus on the swallowing apparatus. This phenomenon may explain the mechanism of some of the failed esophageal peristalsis observed in clinical practice.

Inhibition of progressing primary esophageal peristalsis by pharyngeal water stimulation in humans

BACKGROUND & AIMS: Sensory impulses initiated from the pharynx exert differing effects on the deglutitive apparatus. They have an inhibitory effect on the lower esophageal sphincter but an excitatory effect on the upper esophageal sphincter. The aim of this study was to systematically investigate the effect of pharyngeal sensory impulses evoked by water stimulation on the progressing esophageal peristalsis. METHODS: Sixteen healthy young volunteers were studied in the supine position. The presence of normal peristalsis was verified. Esophageal peristalsis was recorded 3, 6, 9, 12, 15, and 18 cm above the lower esophageal sphincter. Pharyngeal stimulation was performed by injecting a predetermined threshold volume into the pharynx 2 cm above the upper esophageal sphincter, directed posteriorly. The injections were timed to coincide with the arrival of the peristaltic wave induced by dry swallows at respective recording sites. RESULTS: Injection of the threshold volume (0.5 +/- 0.1 mL) stopped the progression of peristalsis at both the striated and smooth muscle esophagus. Topical pharyngeal anesthesia blocked this inhibitory effect (P < 0.01). CONCLUSIONS: Sensory impulses initiated from the pharynx evoked by water injection inhibit the progression of primary esophageal peristalsis. Although the clinical significance of these findings is not determined, they may explain the mechanism of some of the failed esophageal peristalsis. (Gastroenterology 1996 Feb;110(2):419-23)

Inhibition of progressing esophageal peristalsis by pharyngeal water stimulation in humans: [formula omitted], R. Shaker, J. Ren, C. Hofmann, R.C. Arndorfer. MCW Dysphagia Institute, Departments of Medicine and Radiology. Medical College of Wisconsin, Milwaukee, WI

Inhibition of progressing esophageal peristalsis by pharyngeal water stimulation in humans: [formula omitted], R. Shaker, J. Ren, C. Hofmann, R.C. Arndorfer. MCW Dysphagia Institute, Departments of Medicine and Radiology. Medical College of Wisconsin, Milwaukee, WI

Inhibition of resting lower esophageal sphincter pressure by pharyngeal water stimulation in humans

Background/Aims: Normal inhibition of lower esophageal sphincter (LES) tone occurs during swallowing and belching. However, it is known that it may occur independently of these functions. The aim of this study was to characterize the effect of pharyngeal water stimulation on resting LES pressure. Methods: The effect of rapid-pulse and slow continuous intrapharyngeal injection of minute increments of water on the resting tone of the upper and LES of 14 healthy young volunteers was evaluated by concurrent manometry, submental electromyography, and respirography. Results: At a threshold volume, pharyngeal water injection induced an isolated LES relaxation in all volunteers. The threshold volume inducing LES relaxation by rapid-pulse injection, 0.16 ± 0.01 mL, was significantly lower than that with slow continuous injection (0.5 ± 0.05 mL) ( P < 0.05). The duration and magnitude of LES relaxation were not volume dependent. The duration of LES relaxation induced by rapid-pulse injection was significantly longer than that of swallows. Conclusions: Minute amounts of liquid injected into the pharynx induce LES relaxation different from that of the normal swallow. Neither the duration nor the magnitude of this relaxation is volume dependent. Whereas the contribution of this finding to the mechanism of transient LES relaxation remains to be ascertained, it may partially explain the variability of the basal LES pressure.

Hypoxia reinforces laryngeal reflex bradycardia in infants.

The laryngeal chemoreflex involves bradycardia, apnea, swallowing and peripheral vasoconstriction. This reflex was studied in twelve infants, aged 5 days-28 weeks, who had sustained an apparent life-threatening event or were siblings of infants who had died of the sudden infant death syndrome. The bradycardic and apneic components of the reflex were found to be significantly, and sometimes powerfully, reinforced when elicited by pharyngeal water instillation during acute, mild hypoxia (transcutaneous PO2 4.6-8.3 kPa). Apnea duration during normoxia was 0.7-15 sec, and during hypoxia 2-30 sec. Heart rate change ranged from +26% to -21% during normoxia, as compared with -4% to -63% during hypoxia. The percentage change in heart rate was found to inversely correlate with the transcutaneous PO2-level prevailing when the reflex was elicited. The conclusion is that there is a significant reinforcement of the cardiorespiratory adjustments when the laryngeal reflex is activated during simultaneous excitation of the peripheral arterial chemoreceptors. One infant, showing a particularly strong increase of the cardiorespiratory response to laryngeal receptor stimulation during hypoxia, later died of sudden infant death syndrome.