Duodenal Acid Clearance in Humans: Observations Made with Intraluminal Impedance Recording

Duodenal acid clearance appears to be involved not only in the pathogenesis of duodenal ulcer disease but also in functional dyspepsia. Duodenal contractile activity can help to maintain neutral pH in the duodenum by mixing acid with bicarbonate or by aborally transporting the acid load. Intraluminal impedance recording, allowing the detection of nonacid liquid boluses, can be carried out concomitantly with antroduodenal manometry and pH recording and may thus provide useful information about the mechanisms involved in duodenal clearance of endogenous acid and volume boluses. Eight H. pylori-negative healthy volunteers were studied with two catheters positioned across the pylorus, allowing the recording of five impedance signals (one antral, one pyloric, and three duodenal) simultaneously with six pressure signals (two antral, one pyloric, and three duodenal) as well as distal antral and proximal duodenal pH. During phase II of the migrating motor complex, which is known to be associated with the highest duodenal acid exposure, each duodenal acidification event (defined as a pH drop > 2 pH units) was characterized by its maximal amplitude, duration, temporal relationship with antroduodenal manometric events, and relation to impedance variations. Acid was considered to have been cleared from the duodenum when the preacidification pH was restored (± 0.2 unit). A total of 164 duodenal pH drops were recorded during the 323 min of phase II recordings. Eleven percent of the duodenal acidification events were short-lived (< 10 sec). All of these events were temporally associated with a propagated antroduodenal contraction and a short-lived drop in impedance, suggesting rapid aboral passage of the acid bolus. The long-lived duodenal acidification events lasted a mean of 32 sec (range, 25–66 sec). In 90% of these events an antroduodenal propagated contraction was recorded at the time of onset. Repetitive duodenal contractions followed the onset of the long-lived acidification events in 34% of the cases. These remained present until complete clearance of the acid. In 81% of the long-lived acidification events, recovery of the associated impedance drop occurred simultaneously with the pH recovery, suggesting a complete clearance of the bolus. Less frequently (19%), the duodenal pH recovered while the impedance remained low, suggesting that the bolus was not cleared but neutralized. Interdigestive duodenal acidification events usually last about 30 sec. They evoke duodenal contractions in only one-third of cases. Combined pH and impedance recording makes it possible to distinguish between neutralization of acid boluses and their complete total clearance.     

Impedance signature of pharyngeal gaseous reflux

BACKGROUND: Pharyngeal impedance changes induced by various pharyngeal reflux events have not been characterized. OBJECTIVES: To characterize pharyngeal impedance changes induced by participant-perceived belching events. METHODS: We systematically evaluated pharyngeal impedance and pH changes related to 453 belch events in 11 gastroesophageal reflux disease, 10 reflux attributed-laryngitis patients and 16 controls. RESULTS: Of 453 belch events, 362 were analyzable. Of these, 72% occurred within 10 s, 93% within 20 s, 99% within 30 s and 100% within 40 s of the time that participants marked a belch event. In 15% impedance changes in the pharynx preceded, in 12% they were simultaneous and in 73% they occurred after the start of the impedance change in the proximal esophagus. Time interval between the two events ranged between 0.4+/-0.03 and 0.7+/-0.1 s. In all, there were three types of belch-induced impedance changes: (a) impedance increase, (b) impedance decrease and (c) multiphasic. Twenty percent of impedance events associated with belching had less than 50% change from baseline, whereas in 51% changes exceeded or were equal to 50%. Among events with a drop in pharyngeal impedance, only two satisfied the criteria for the liquid reflux event. CONCLUSIONS: Pharyngeal ventilation of gastric gaseous content seems to have a unique impedance signature. During pharyngeal gas reflux events, impedance changes may start before or after proximal esophageal changes. Belching may induce negative pharyngeal changes that do not meet the criteria for liquid reflux. These findings need to be taken into consideration in the analysis of pharyngeal reflux events.     

Viscosity of food boluses affects the axial force in the esophagus

AIM: To study the effect of viscosity on axial force in the esophagus during primary peristalsis using a newly validated impedance-based axial force recording technique. METHODS: A probe able to simultaneously measure both axial force and manometry was positioned above the lower esophageal sphincter. Potable tap water and three thickened fluids were used to create boluses of different viscosities. Water has a viscosity of 1 mPa·s. The three thickened fluids were made with different concentrations of Clinutr...     

Impedance characteristics of esophageal motor function in achalasia

Detailed data on patterns of esophageal bolus transport in patients with achalasia are still lacking. To study these we applied the novel technique of multichannel intraluminal impedance measurements. Ten patients with achalasia were studied using a 16 channel system. Liquid and semisolid boluses of 10 mL were applied with the patients in a supine position. Patterns of bolus transport were determined and analyzed as compared to results obtained from 20 healthy subjects. The healthy subjects featured a unique typical primary peristalsis pattern independent of bolus viscosity. In contrast, achalasia patients demonstrated different impedance characteristics, including: (i) significantly lower baseline esophageal impedance during the resting state as compared with healthy volunteers (999 omega +/- 108 versus 2749 omega +/- 113); (ii) failed bolus transport through the esophagus in all cases; (iii) impedance evidence of luminal content regurgitation in 35% of the swallows (iv) impedance evidence of pathological air movement within the proximal esophagus during deglutition in 38% of the swallows, so called air trapping. Thus, impedance characteristics of achalasia have been defined and can be attributed to known symptoms of achalasia. They can be used as basic findings for further classification of pathological bolus transports in other esophageal motility disorders.     

Effect of Bolus Volume and Viscosity on Pharyngeal Automated Impedance Manometry Variables Derived for Broad Dysphagia Patients

Automated impedance manometry (AIM) analysis measures swallow variables defining bolus timing, pressure, contractile vigour, and bolus presence, which are combined to derive a swallow risk index (SRI) correlating with aspiration. In a heterogeneous cohort of dysphagia patients, we assessed the impact of bolus volume and viscosity on AIM variables. We studied 40 patients (average age = 46 years). Swallowing of boluses was recorded with manometry, impedance, and videofluoroscopy. AIMplot software was used to derive functional variables: peak pressure (PeakP), pressure at nadir impedance (PNadImp), time from nadir impedance to peak pressure (TNadImp-PeakP), the interval of impedance drop in the distal pharynx (flow interval, FI), upper oesophageal sphincter (UES) relaxation interval (UES RI), nadir UES pressure (Nad UESP), UES intrabolus pressure (UES IBP), and UES resistance. The SRI was derived using the formula SRI = (FI * PNadImp)/(PeakP * (TNadImp-PeakP + 1)) * 100. A total of 173 liquid, 44 semisolid, and 33 solid boluses were analysed. The SRI was elevated in relation to aspiration. PeakP increased with volume. SRI was not significantly altered by bolus volume. PNadImp, UES IBP, and UES resistance increased with viscosity. SRI was lower with increased viscosity. In patients with dysphagia, the SRI is elevated in relation to aspiration, reduced by bolus viscosity, and not affected by bolus volume. These data provide evidence that pharyngeal AIM analysis may have clinical utility for assessing deglutitive aspiration risk to liquid boluses.     

Performance and optimal technique for pharyngeal impedance recording: A simulated pharyngeal reflux study

BACKGROUND AND AIMS: Detection rate, influence of recording site, and subject posture for impedance monitoring of pharyngeal reflux of gastric contents remain unknown. We evaluated the ability of the impedance sensor for detection of various volumes of intrapharyngeal infusate at two sites and in two subject positions. METHODS: Nineteen healthy subjects were studied using concurrent videoendoscopic, manometric, impedance, and pH recording. RESULTS: Detection rate of simulated pharyngeal reflux events ranged between 87% and 100% for 1-4 mL. Detection rate for 0.1-1 mL volumes in the upright position was significantly higher (78-85%) when the impedance sensor was located at the proximal margin of the upper esophageal sphincter (UES) compared to 2 cm proximally (38-68%) (P < 0.001). With the sensor at 2 cm above the UES, the average detection rate for all volumes in the upright position was significantly less (P < 0.001) compared to the supine position (48%vs 84%). There was substantial variability in the magnitude of impedance changes induced by different infusates. CONCLUSIONS: Impedance sensors can detect as small a volume as 0.1 mL and combined with a pH sensor can detect acidic and nonacidic liquid and mist reflux events. Sensor placement at the proximal margin of the UES yields the highest detection rate irrespective of subject posture compared to placement 2 cm proximally. Depending on the volume of refluxate and location of the impedance sensor, a substantial minority of simulated reflux events can be missed.     

Esophageal solid bolus transit: studies using combined multichannel intraluminal impedance and manometry in healthy volunteers

The purpose of this study is to apply combined multichannel intraluminal impedance and esophageal manometry (MII‐EM) to test esophageal function during solid swallowing in a normal healthy population. We determined whether combined MII‐EM with solid bolus is more sensitive than that with viscous bolus in the detection of motility abnormality. Eighteen healthy volunteers (11 men and 7 women; mean age 22 years, range 20–26 years) underwent combined MII‐EM with a catheter containing four impedance‐measuring segments and five solid‐state pressure transducers. Each subject received 10 viscous and 10 solid materials. Tracings were analyzed manually for bolus presence time, total bolus transit time, contraction amplitude, duration, and onset velocity. Three hundred and sixty swallows including viscous and solid materials were analyzed. Contraction amplitude for the viscous swallows was higher at 20 cm above the lower esophageal sphincter (LES) (P= 0.049) but lower at 15 cm above the LES (P < 0.001). Duration of contractions for the solid swallows was longer at 15 cm (P= 0.002) and 10 cm above the LES (P= 0.011) compared with viscous swallows. The total bolus transit time for solid was significantly shorter than that for viscous boluses (6.8 vs. 7.7 seconds, P < 0.001). Bolus presence time appeared to be similar between viscous and solid boluses (except in the proximal esophagus). The percentage of swallows with ineffective peristalsis by manometry, as well as those with incomplete bolus transit by impedance, did not differ between viscous and solid swallows. The proportion of manometrically ineffective solid swallows with incomplete bolus transit was greater than that of viscous swallows (62.1% vs. 34.8%, P= 0.05). Application of solid boluses may potentially enhance diagnostic capability of esophageal function testing. Solid boluses can be regarded as a valuable complement to viscous boluses in the detection of esophageal motility abnormalities when applied with combined MII‐EM.     

Impedance nadir values correlate with barium bolus amount

We examined the value of impedance monitoring in measuring bolus volume compared with videoesophagram. Eighty consecutive subjects were studied with simultaneous impedance‐manometry‐videoesophagram. A catheter with both an impedance electrode pair and a pressure transducer at four sites (5, 10, 15, 20 cm above lower esophageal sphincter) was passed per nares. Six 10‐cc boluses of 45% barium mixed with 0.9% NaCl were swallowed at 20‐ to 30‐second intervals. When impedance fell to below 1000 ohms, other than that occurring during administered swallows, the videofluoroscopic image corresponding to the time of impedance nadir was reviewed. If barium was present at the impedance site, barium area was calculated. The video was reviewed for the cause of abnormal barium transit causing barium presence. We found 38/80 subjects had a total of 169 impedance falls to below 1000 ohms. Ninety‐seven percent (164/169) of impedance falls had barium present at the impedance site, and there was good correlation (r = 0.83, P < 0.001) between impedance nadir value and barium area. The impedance nadir value : barium area relationship was similar for the three causes of barium presence identified by video: failed bolus clearing; gastroesophageal reflux; and esophageal escape. Impedance nadir values 700–999 ohms usually had a small barium area. In contrast, nadir values <400 ohms had a large barium area covering all or most of the catheter and filling the esophagus at the impedance site. Impedance falls from >1000 ohms to a low nadir value from all forms of abnormal esophageal bolus transit imply a large bolus amount.     

Stimulation and characteristics of secondary oesophageal peristalsis in normal subjects.

The study evaluates the triggering and characteristics of secondary oesophageal peristalsis in 25 healthy volunteers. Secondary peristalsis was stimulated by rapid intraoesophageal injection of boluses of air and water, and by a five second oesophageal distension with a balloon. Air and water boluses triggered secondary peristalsis that started in the proximal oesophagus regardless of injection site. Response rates were volume dependent with 83% of the 20 ml air boluses triggering secondary peristalsis compared with 2% for the 2 ml water bolus (p < 0.0001). Response rates for air and water were similar for equal bolus volumes and were not influenced by the site of injection. In contrast, balloon distension usually induced a synchronous contraction above the balloon, with secondary peristalsis starting below the balloon after deflation. The peristaltic response rate to balloon distension was also volume dependent and the middle balloon was more effective in triggering secondary peristalsis than either the upper or lower balloons (p < 0.001). Secondary peristaltic amplitude was less than that of primary peristalsis (p < 0.001). Secondary peristaltic velocity with a water bolus was slower (p = 0.001) than that of primary peristalsis. Intravenous atropine significantly reduced secondary peristaltic responses to all stimuli. There was also a significant reduction in pressure wave amplitude for air stimulated secondary peristalsis while those for the water responses were similar. Secondary peristaltic velocity with air and water boluses was not changed by atropine. The reproducibility of testing secondary peristalsis was examined six volunteers and did not show any significant differences on separate test days in response rate and peristaltic amplitude or velocity. It is concluded that in normal subjects, secondary peristalsis can be more reliably triggered by intraoesophageal air or water infusion than balloon distension. Secondary peristaltic amplitude and velocity are stimulus but not site or volume dependent and propagation is partially mediated by cholinergic nerves.     

Association of pulse waveform characteristics with birth weight in young adults

OBJECTIVE: An association between birth weight and blood pressure has been reported in many studies, but the strength of this association has been disputed. Birth weight could, however, be associated with alterations in the proximal arterial tree that have little effect on blood pressure. The objective of this study was to examine the relationship between birth weight and characteristics of the proximal arterial tree determined by pulse wave analysis. METHODS: An optically derived digital volume pulse was used to obtain indices of pressure wave reflection (reflection index; RI) determined by characteristics of small/medium sized arteries and of large artery stiffness (stiffness index; SI) in healthy young adults (n = 220, 111 women, aged 16-26 years). Birth weight was obtained from maternal recall. RESULTS: Diastolic blood pressure was significantly correlated with birth weight (P < 0.001) but birth weight accounted for only 5% of the variance in diastolic blood pressure. RI was significantly correlated with birth weight in women (r = -0.33, P < 0.001) but not in men, and there was a significant interaction between birth weight and sex (P < 0.001). SI was significantly independently correlated with birth weight in both men and women (r = -0.41 and -0.49, each P < 0.0001) and birth weight accounted for 17% of the overall (men and women) variance in SI. CONCLUSIONS: These results suggest a close association between birth weight and characteristics of the arterial tree proximal to resistance vessels in young adults and a sex-specific association with characteristics influencing arterial pressure wave reflection.     

Effect of crystalloid infusion on hematocrit and intravascular volume in healthy, nonbleeding subjects

We evaluated the effect of IV crystalloid administration on hematocrit in 28 healthy, nonbleeding volunteers. Normal saline boluses of 10, 20, and 30 mL/kg were delivered at a mean rate of 115 +/- 4 mL/min, followed by a continuous infusion of either 1 or 5 mL/kg/hr. Hematocrit values determined immediately after bolus infusion declined from baseline a mean +/- SEM of 4.5 +/- 0.6 (P less than .001), 6.1 +/- 0.4 (P less than .001) and 6.3 +/- 0.6 points (P less than .001) in the 10, 20, and 30 mL/kg groups, respectively. Twenty minutes into the maintenance infusion, hematocrits had risen 1.5 +/- 0.8 (P = .03), 2.4 +/- 0.4 (P = .004) and 2.3 +/- 0.7 points (P = .005) when compared with post-bolus hematocrits in the 10, 20, and 30 mL/kg groups, respectively. These data show that in healthy, nonbleeding subjects, crystalloid infusion may cause significant changes in hematocrit. Calculations reveal that approximately 60% of infused saline, when delivered as a bolus, will diffuse from the intravascular space within 20 minutes of administration.     

Effects of Bolus Volume on Pharyngeal Contact Pressure During Normal Swallowing

This cross-sectional study investigated the effect of bolus volume on contact pressure within the pharynx and upper esophageal sphincter (UES). Three solid-state manometric pressure sensors were placed transnasally into the pharynx and the proximal esophagus of 40 participants (gender equally represented and between the ages of 20 and 45 years). Participants completed five repetitions each of three swallowing conditions: 5-, 10-, and 20-ml water bolus swallows. Repeated-measures ANOVA revealed no significant differences in the amplitude of pharyngeal contact pressure between the three swallowing conditions (sensor 1: p = 0.627, sensor 2: p = 0.764). Similarly, for durational measures nonsignificant main effects were found at both sensor 1 (p = 0.436) and sensor 2 (p = 0.350). Significant differences were found in UES pressure between the three conditions of bolus swallows (p = 0.000), with negative pressure in the UES inversely proportionate to bolus volume. However, durational measures of UES relaxation pressure were not significantly different between all conditions (p = 0.473). This study demonstrates no significant pressure differences of amplitude and duration between swallowing conditions in the pharynx. At the level of the UES, smaller boluses generated greater negative pressure.     

Bronchoscopic thermal vapour ablation therapy in the management of heterogeneous emphysema

The need for a less invasive procedure than surgical lung volume reduction that can produce consistent improvements with reduced morbidity remains a medical goal in patients with emphysema. We sought to determine the effect of bronchoscopic thermal vapour ablation (BTVA) on lung volumes and outcomes in patients with emphysema. 44 patients with upper lobe-predominant emphysema were treated unilaterally with BTVA. Entry criteria included: age 40-75 yrs, forced expiratory volume in 1 s (FEV(1)) 15-45% predicted, previous pulmonary rehabilitation and a heterogeneity index (tissue/air ratio of lower lobe/upper lobe) from high-resolution computed tomography (HRCT) ≥ 1.2. Changes in FEV(1), St George's Respiratory Questionnaire (SGRQ), 6-min walk distance (6 MWD), modified Medical Research Council (mMRC) dyspnoea score, and hyperinflation were measured at baseline, and 3 and 6 months post-BTVA. At 6 months, mean ± SE FEV(1) improved by 141 ± 26 mL (p<0.001) and residual volume was reduced by 406 ± 113 mL (p<0.0001). SGRQ total score improved by 14.0 ± 2.4 points (p<0.001), with 73% improving by ≥ 4 points. Improvements were observed in 6 MWD (46.5 ± 10.6 m) and mMRC dyspnoea score (0.9 ± 0.2) (p<0.001 for both). Lower respiratory events (n=11) were the most common adverse event and occurred most often during the initial 30 days. BTVA therapy results in clinically relevant improvements in lung function, quality of life and exercise tolerance in upper lobe predominant emphysema.     

Insulin sensitivity and secretion influence the relationship between growth hormone-binding-protein and leptin

BACKGROUND: A direct relationship between body mass index (BMI), visceral adipose tissue, insulin levels and growth hormone-binding protein (GHBP) activity has consistently been reported. It was recently described that GHBP directly depends on serum leptin levels. Since leptin co-varies with insulin secretion and/or sensitivity, we aimed to study the influence of these variables on plasma GHBP activity. SUBJECTS: In order to isolate the effects of obesity per se from those of insulin secretion, three groups of subjects were prospectively studied: 14 lean, 10 obese and nine obese subjects with glucose intolerance. MEASUREMENTS: The percentage of body fat was measured through bioelectric impedance. Insulin sensitivity and secretion were determined through a frequently sampled intravenous glucose tolerance test with minimal model analysis. Serum leptin was measured by radioimmunoassay. GHBP activity was determined by the high performance liquid chromatography-gel filtration method. RESULTS: Plasma GHBP activity was found to correlate with BMI (r = 0. 65, P < 0.0001), fat mass (r = 0.51, P = 0.003), waist circumference (r = 0.64, P < 0.0001), waist-to-hip ratio (r = 0.42, P = 0.01), insulin sensitivity (SI, r = - 0.61, P = 0.0001), insulin secretion (expressed as the acute insulin response to intravenous glucose, AIRg) (r = 0.48, P = 0.006) and leptin concentration (r = 0.49, P = 0.004). The associations with SI (r = - 0.42, P = 0.02) and AIRg (r = 0.38, P = 0.03) persisted even after controlling for fat mass. Since insulin secretion and insulin sensitivity usually covary in glucose tolerant subjects (an increased insulin secretion is necessary to compensate a decreased insulin sensitivity), we constructed a multiple linear regression to predict GHBP activity. In this model, SI (P = 0.005), AIRg (P = 0.02) and SD score-leptin (P = 0.03) independently contributed to 34, 10 and 8% of the variability in serum GHBP activity. CONCLUSIONS: Our results suggest that plasma GHBP activity is simultaneouslly influenced by insulin secretion and sensitivity and leptin. Perhaps leptin, through increased insulin secretion, might induce GHBP/GH secretion, explaining the normal to high insulin-like growth factor (IGF)-I levels found in overnutrition.     

Disagreement between symptom-reflux association analysis parameters in pediatric gastroesophageal reflux disease investigation

AIM: To assess the agreement within 3 commonly used symptom-reflux association analysis (SAA) parameters investigating gastroesophageal reflux disease (GERD) in infants. METHODS: Twenty three infants with suspected GERD were included in this study. Symptom index (SI), Symptom sensitivity index (SSI) and symptom association probability (SAP) related to cough and irritability were calculated after 24 h combined pH/multiple intraluminal impedance (MII) monitoring. Through defined cutoff values, SI, SSI and SAP...     

体外循环动脉微栓过滤器性能离体实验研究

目的:通过离体实验评价成人型动脉滤器(QUART)、米道斯动脉滤器(MEDOS)和宁波动脉微栓滤器的跨滤器压差和气泡去除能力。方法:分别选用QUART、MEDOS和宁波3种动脉过滤器各15个,依次为QG组、MG组和NG组,连接模拟体外循环管路,使用1 000 mL0.9%氯化钠预充环路,并在管路上连接Stockert气泡捕捉器。同时在动脉滤器的入口端、出口端和排气管处连接电子测压仪,使用管钳维持动脉滤器出口处压力为80 mmHg(1 mmHg=0.133 kPa),测定动脉滤器入口端、出口端和排气管处的压力。在流量为5.0 L/min时,于动脉滤器入口处每隔1 min加入10 mL空气,最多不超过80mL。结果:预充后NG组中9个(9/15,60.0%)动脉微栓滤器发出报警音,明显高于QG组和MG组,差异具有统计学意义(P<0.05);首次倒排时,QG、MG和NG组分别有1/15(6.7%)、13/15(86.7%)和15/15(100.0%)发出报警音,QG组明显低于MG组和NG组,差异具有统计学意义(P<0.05)。随着主泵流量的增加,3种动脉滤器入口端压力、出口端压力及压差均逐渐升高。相同流量下,3种动脉滤器入口端压力、出口端压力和压差差异均无统计学意义(P>0.05);流量为5 L/min,3组动脉滤器分别加入气体至80 mL时均未发出报警音。结论:使用动脉滤器时,排气需要2遍以上,才能安全使用。正常转机流量下,3种动脉滤器跨滤器压差基本相同。3种动脉滤器均有较强的气泡隔离能力。     

Postprandial hyperglycaemia following insulin suspensions by the artificial pancreas: Implications for bolus calculators

Conventional bolus calculators apply negative prandial corrections when premeal glucose levels are low. However, no study has evaluated the need for this negative correction with closed-loop systems. We analysed data retrospectively from a cohort study evaluating a closed-loop artificial pancreas system conducted in a diabetes camp over a period of 11 days. Meal boluses with negative correction (n = 98) of 47 participants aged 8 to 22 years were examined. If there was no insulin-on-board from previous boluses at mealtime, the postprandial hyperglycaemia rate increased with increased duration of insulin suspension (P = .03), with odds ratios being exaggerated by 17% per 10 minutes of suspension. However, if there was insulin-on-board from previous boluses, the hyperglycaemia rate did not change with increased duration of insulin suspension (P = .24). When there was no insulin-on-board, the rate of hyperglycaemia after meals preceded by no suspension was 21% (3/14), compared with 52% (12/23) and 64% (9/14) after meals preceded by suspensions of ≥50 and ≥70 minutes, respectively. Meal size did not influence these results. We conclude that, in the absence of insulin-on-board, negative prandial corrections may not be necessary following long insulin suspensions.     

Modulation of intestinal gas dynamics in healthy human volunteers by the 5-HT receptor agonist tegaserod

OBJECTIVES: Bloating in irritable bowel syndrome (IBS) may result from impaired intestinal gas transit and is reduced by the 5-HT4 agonist tegaserod. Abnormal serotonergic function underlies many IBS symptoms, but the role of 5-HT4 pathways in regulating gas dynamics under healthy conditions is unexplored. We hypothesized that 5-HT4 activation by tegaserod stimulates gas transit in healthy individuals. METHODS: Sixteen normal volunteers underwent jejunal perfusion of gas mixtures (88% N2, 5.5% O2, 6.5% CO2) at 11.2 mL/min x 3 h under control conditions and 3 h after oral tegaserod 6 mg on separate days. Gas collected from an intrarectal catheter was quantified using a barostat. RESULTS: Under control conditions, gas evacuation after a lag period (1,959 +/- 428 s) was predominantly pulsatile with expulsion of 1,984 +/- 90 mL. A mean of 29 +/- 2 boluses with volumes of 72 +/- 5 mL were expelled. In 10 subjects with physiologic degrees of gas retention in control studies (248 +/- 73 mL), tegaserod increased expulsion from 1,768 +/- 73 to 1,973 +/- 37 mL and decreased retention to 43 +/- 37 mL (p < 0.05). Total volumes expelled as boluses were greater after tegaserod (1,708 +/- 73 vs 1,846 +/- 59 mL, p < 0.05) from increased bolus numbers in four subjects and increased bolus volumes in seven. Nonpulsatile continuous flow tended to increase with tegaserod (43 +/- 7 vs 126 +/- 43 mL, p= 0.10). Tegaserod did not increase evacuation in individuals without physiologic gas retention. CONCLUSIONS: The 5-HT4 agonist tegaserod promotes evacuation of jejunally perfused gas mixtures in healthy humans. These findings provide the foundation for future investigations into use of 5-HT4 agonists in conditions of pathologic gas retention.     

Relationship between pressure wave amplitude and esophageal bolus clearance assessed by combined manometry and multichannel intraluminal impedance measurement

OBJECTIVES: Esophageal wave amplitude is an important determinant of esophageal clearance. A threshold of 30 mmHg is widely accepted as the threshold for effective clearance in the distal esophagus. However, the precise relationship between wave amplitude and clearance has received relatively little attention. The aim of this study was to assess the impact of peristaltic wave amplitude on esophageal volume clearance using multiple intraluminal impedance (MII) measurement. METHODS: Concurrent manometry and MII were performed on 42 healthy asymptomatic volunteers and 13 patients with ineffective esophageal motility. Esophageal motility was measured at four sites 5-cm apart, starting 2 cm above the lower esophageal sphincter. MII was measured at corresponding sites with electrodes incorporated into the manometric assembly. Ten 5-mL liquid (saline) boluses and ten 5-mL low impedance viscous boluses were tested in each subject. Pressure wave amplitude was determined at each site as well as peristaltic success of the responses. Bolus clearance was measured from individual recording segment and from the esophagus as a whole. RESULTS: The proportion of liquid boluses cleared at each site was directly related to wave amplitude and did not increase significantly above a threshold of 25 mmHg in the proximal esophagus, 22 mmHg in the mid-esophagus, and 30 mmHg in the distal esophagus. Corresponding wave amplitudes for total esophageal clearance were 35-40 mmHg. There was a good correlation between the wave amplitude at one site of the esophagus and those of the rest of the esophagus. For both liquid and viscous boluses, the likelihood of impaired clearance was directly related to the number of segments with hypotensive pressure waves. CONCLUSION: The findings confirm the validity of the wave amplitude threshold required for effective liquid bolus clearance and have established the amplitude threshold for clearance of viscous boluses. However, the number of hypotensive pressure waves required for the definition of ineffective motility may be too low.     

Effect of cystic fibrosis on inhaled aerosol boluses

An aerosol bolus undergoes changes in shape between its inspiration and expiration. In comparison with the inhaled bolus, the exhaled bolus is more spread because of convective mixing, may have a shift in the location of the mode caused by asymmetries of filling and emptying of lung units, and contains fewer particles because of particle deposition. We hypothesized that the extent of these changes is related to lung health. To examine this, 11 patients with cystic fibrosis (CF) and 11 healthy subjects inhaled 70 cm3 boluses containing 1 micron monodisperse particles that were inspired to volumetric penetrations (Vp) of 100 to 700 cm3. As each bolus was expired, we measured spreading (volumetric width at one-half aerosol concentration peak height), modal shift, and particle deposition. Patients with CF exhaled boluses that were broader than those exhaled by normal subjects at all penetrations examined. At a Vp of 600 cm3, patients had a mean bolus half-width that was 68% greater than that of healthy subjects (p less than 0.0001), and they exhaled the bolus mode 20% earlier (p less than 0.0002). Particle deposition was increased compared with that in normal subjects at all Vp. For example, mean deposition at a Vp of 600 cm3 was 46.2 +/- 2.6% (SE) for the patients versus 25.8 +/- 1.6% for the normal subjects (p less than 0.0001). Among the patients with CF, pulmonary function parameters indicating obstruction were significantly correlated with bolus spreading and aerosol deposition: the percent predicted FEV1/FVC was inversely correlated with spreading (r = -0.88, p less than 0.0004) and deposition (r = -0.84, p less than 0.0008).(ABSTRACT TRUNCATED AT 250 WORDS)