Nadir pH Research Articles

Comparison of Proximal Migration of Sensed Reflux Events Among the Different GERD Groups

Background: Proximal migration, nadir of pH, and duration have been shown to increase the likelihood of experiencing a sensed reflux event (SRE). Thus far, there are no studies comparing SRE characteristics among the different GERD groups. Aim: To compare the proximal migration characteristics of SRE among the different GERD groups. Methods: Patients with typical heartburn symptoms at least 3 times a week for more than 3 months were recruited to this study. Upper endoscopy and pH testing were used to divide the patients into three groups: erosive esophagitis (EE), nonerosive reflux disease (NERD), and functional heartburn (FH). Patients underwent esophageal pH testing using a 4-sensor pH probe. The most distal pH sensor was positioned 1 cm > LES, and the sensors were located 5 cm apart (6 cm, 11 cm, 16 cm > LES). Results: A total of 22 patients had EE, 15 NERD, and 13 FH (M/F - 20/2, 12/3, 5/8, mean age - 51.5 ± 3.7, 50.1 ± 4.2, 50.3 ± 3.8, respectively). During the pH test, 143 GERD-related symptoms were reported, 112 (78.3%) were correlated with pH < 4 at the very distal pH sensor and thus were considered as SRE. Patients with FH experienced 12, NERD 33 and EE 67 SREs. Of the 112 SREs, 97(86.6%) reached 6 cm > LES, 83(74.1%) - 11 cm > LES, and 59(52.7%) −16 cm > LES. In FH, 75% of the SREs reached 16 cm > LES as compared to 57.6% in the NERD group and 46.3% in EE group (p < 0.01). In contrast, only 28%, 26%, and 26% of the non-SREs of patients with FH, NERD, and EE, respectively, reached 16 cm > LES (P < 0.01). In all groups, duration of SRE 1 cm and 6 cm > LES was significantly higher than duration of non-SRE (5.9 ± 1.1 vs. 3.4 ± 0.5 and 5.2 ± 1.1 vs. 2.2 ± 0.3, respectively, p < 0.001). Additionally, SREs had a significantly lower pH nadir and change in pH at 1 cm>LES then non-SREs (0.96 ± 0.07 vs. 1.4 ± 0.05 and 4.9 ± 0.2 vs. 4.6 ± 0.01, respectively, p < 0.05). Conclusion: Patients with FH demonstrated the highest number of SREs that reach proximal esophagus, as compared to those with EE and NERD. Overall, SREs are more associated with longer duration, pH nadir, and change in pH 1 cm > LES as compared to non-SREs.

When are reflux episodes symptomatic?

Careful scrutiny of pH recordings and symptom diaries in patients having 24-hour pH-metry reveals that most reflux episodes are asymptomatic. Although this observation is well known and long recognized, the explanation for why one reflux episode leads to symptoms and others do not is incompletely understood. Forty-four patients with chronic typical gastroesophageal reflux disease (GERD) symptoms referred for ambulatory pH testing were studied. Antisecretory medication was stopped 2 weeks prior to the study. Two meals were taken during the study; one standardized (hamburger, fries, milk-shake) and one at the patient's discretion. A system onset marker noted the type, beginning and end of symptoms (heartburn, regurgitation, chest pain). Age, sex, upright/supine position, nadir pH, time pH < 4, and relationship to meals were compared for symptomatic/asymptomatic reflux episodes. An acid reflux event was defined as a drop in pH < 4 lasting > 5 seconds. The pH catheter detected 1464 reflux episodes. Only 93 (6.3%) were symptomatic. Forty-six of the 93 (49.4%) were associated with heartburn, 38 (40.9%) with regurgitation, and nine (9.7%) with chest pain. Nadir pH was significantly lower in symptomatic episodes. Nearly 50% of symptomatic reflux episodes occurred after meals, especially after non-standardized compared to standardized meal. Symptomatic episodes tended to be longer in duration and to occur in the supine position, while age/sex made no difference. Six percent of the reflux episodes were temporally associated with typical GERD symptoms. This association seems to be influenced by the acidity of the refluxate. Nearly half of the symptomatic reflux episodes occurred after eating.

Diurnal Variation in the Chemical Clearance of Acid Gastroesophageal Reflux in Infants

Clearance of acid gastroesophageal reflux is biphasic. During volume clearance, refluxed material is cleared from the esophagus by peristalsis, and during chemical clearance, acidified esophageal mucosa is neutralized by saliva and possibly secretions from the esophageal lumen. In this study, we examined the effects of feeding on the durations of volume clearance and chemical clearance. Combined pH/multichannel intraluminal impedance tracings from 12 symptomatic infants (median age, 20 weeks) were analyzed. Acid gastroesophageal reflux episodes having both volume clearance and chemical clearance components were grouped into 1 of 4 feeding cycle phases (feeding, first hour postprandial, second hour postprandial, and fasting). Mean duration of volume clearance and chemical clearance was 7.0 +/- 2.3 and 36.3 +/- 8.5 minutes (P = .001), respectively, per patient and 24.7 +/- 2.7 and 127.5 +/- 10.7 seconds (P < .0001), respectively, per episode. Whereas volume clearance did not change throughout the feeding cycle, chemical clearance was significantly prolonged during fasting (132.2 +/- 18.4 seconds) compared with feeding (13.5 +/- 4.1 seconds, P = .0046) and 1st postprandial (64.0 +/- 19.4 seconds, P = .0333). Statistical analysis failed to demonstrate a significant relationship between nadir pH and chemical clearance (P = .3104) or between chemical clearance and the interaction between nadir pH and feeding cycle. Chemical clearance is significantly prolonged during fasting in infants. Falling pH alone cannot explain declining chemical clearance efficiency during later postprandial periods. We speculate that inefficient chemical clearance during fasting is likely due to reduced efficiency of acid clearance mechanisms that could include salivation, swallowing, peristalsis, and/or intraluminal secretion.

Addition of Esophageal Impedance Monitoring to pH Monitoring Increases the Yield of Symptom Association Analysis in Patients off PPI Therapy

The additional yield of esophageal impedance monitoring in identification of reflux as the cause of reflux symptoms is unknown. To compare the yield of symptom-reflux association analysis of combined esophageal pH-impedance data with the yield of analysis of pH data alone. In 60 patients with symptoms of heartburn and regurgitation combined, 24-h pH-impedance monitoring was performed. Acid-suppressive medication was stopped 1 wk in advance. Patients (48) with at least one symptom during the measurement period were selected for further analysis. Patients were instructed to note the time and nature of their symptoms. Eleven types of reflux episodes were defined, based on combinations of magnitude of the pH drop, nadir pH, and nature of the refluxate (gas and liquid) on impedance tracings. Symptom association analysis-symptom index, the symptom sensitivity index, and the symptom association probability (SAP)-was performed for each definition of reflux. The proportion of patients with a positive SAP (> or =95.0%) varied between 62.5% and 77.1%, depending on the definition of reflux episodes. When both pH and impedance parameters were used to identify reflux, a higher proportion of patients had a positive SAP than with pH alone (77.1%vs 66.7%, p < 0.05). Symptom association analysis for acidic and weakly acidic reflux separately did not result in a higher yield than analysis with all reflux episodes pooled, regardless of pH. In patients off proton pump inhibitor, the addition of impedance monitoring to esophageal pH monitoring leads to an increase in the proportion of patients in whom an association between reflux episodes and symptoms can be identified.

Ingestion of Acidic Foods Mimics Gastroesophageal Reflux During pH Monitoring

Ingestion of acidic foods may produce artifactual drops in pH to < 4 that may be difficult to differentiate from a true acid reflux event. We aimed to evaluate intraesophageal pH changes during the ingestion of acidic food and describe the frequency and implications of acidic food ingestion on ambulatory pH monitoring. Ten normal volunteers (six females; mean age, 34) underwent combined impedance-pH testing with a pH electrode placed 5 cm above the lower esophageal sphincter. Each volunteer received 50 ml each of acidic foods in random order. Nadir and mean pH for 30 sec after ingestion of each substance were recorded. Subsequently 100 randomly selected reflux monitor diaries were reviewed, searching for ingestion of acidic foods, and 100 pH tracings were reviewed to evaluate the impact of including/excluding meal periods on percentage time pH < 4 and DeMeester scores. All foods produced abrupt drops to pH < 4, in 80% of cases exceeding 30 sec. During ambulatory pH monitoring 78% of patients recorded ingestion of at least 1 of the 10 tested substances during meals, the majority admitting ingesting carbonated beverages. Not excluding meal periods would have led to the misinterpretation of 6-16% of tracings, depending on the criteria used to identify abnormal acid exposure. We conclude that ingestion of acidic foods is frequent and carries the risk of overdiagnosing GERD. Current findings support the recommendations to carefully instruct patients to record all oral intake and to exclude meal periods from the analysis.

Noninvasive ventilation for hypercapnic respiratory failure in COPD: Encephalopathy and initial post-support deterioration of pH and PaCO2 may not predict failure

Objectives: To correlate the degree of encephalopathy, baseline values of PaCO2 and pH, and their early response to NIV with eventual in-hospital outcome in patients of severe acute-on-chronic hypercapnic respiratory failure in COPD. Design: Retrospective review. Setting: Intensive care unit. Material and methods: 24 episodes of acute exacerbation of COPD in 17 patients (10 females, 7 males) with a mean age of 59.5 years (range 48 - 82) where NIV was initiated. Data collected: encephalopathy score at baseline and at 24 hours, respiratory rate, breathing pattern, serial arterial blood gases, duration of NIV support per day and hospital days. Results: All patients had severe hypercapnia (mean peak PaCO2 89.0 mm Hg ± 21; range 66-143), respiratory acidosis (mean nadir pH 7.24 ± 0.058, range 7.14 - 7.33) and tachypnoea (mean respiratory rate 29.5 ± 4.69/mt; range 24 - 40). In 17 episodes, altered mental state was present (encephalopathy score 1.92 ± 1.32, median 2.5). Clinically stable condition occurred over several days (mean 13± 9.6 days; range 5 - 40). Intubation was avoided in 22 out of 24 episodes (91.6%) despite significant initial worsening of PaCO2 and pH. Two patients died. The mean time on NIV was16.5 hours/day (range 4 - 22). Conclusions: In selected patients of COPD with acute hypercapnic failure on NIV worsening PaCO2 and pH in the initial hours may not predict failure provided the level of consciousness and respiratory distress improve.

Multipoint measurement of intragastric pH in healthy preterm infants

Background: The diagnostic use of 24 hour oesophageal pH monitoring in infants is controversial because of the impact of feed buffering of gastric acidity. Aim: To re-evaluate the effect of...

Influence of Yeast Culture on Ruminal Microbial Metabolism in Continuous Culture

A continuous culture study was conducted to evaluate the effect of two different yeast cultures on ruminal microbial metabolism. The treatments were a) control lactation ration, b) yeast culture 1 (YC1, Diamond-V XP) and c) yeast culture 2 (YC2, A-Max), both fed at an equivalent of 57 g/head per day. The results showed that both yeast culture products increased dry matter (DM) digestion, propionic acid production, and protein digestion compared with the control. Yeast culture 1 demonstrated an increase in molar percentage of propionic acid, a reduction in acetic acid, and a lower mean nadir (daily low) pH compared with YC2. Ruminal cultures treated with YC digested more protein and contributed less bypass N than control. Supplementing YC2 resulted in a tendency for higher microbial N/kg DM digestion than YC1. Yeast culture 1 resulted in production of rumen microbes containing less protein and more ash than YC2. These results support previous research findings that yeast culture does influence microbial metabolism, and specific yeast cultures may have different modes of action.

Ruminal Supplementation of Direct-Fed Microbials on Diurnal pH Variation and In Situ Digestion in Dairy Cattle

To evaluate the effect of direct-fed microbial (DFM) concentration on diurnal rumen pH profiles and in situ digestibilities, nine ruminally cannulated cows in early lactation were fed treatments consisting of DFM (Enterococcus faecium, Lactobacillus plantarum, and Sacchromyces cerevisiae) at a level of a) 1 × 105 cfu/ml of rumen fluid (105), b) 1 × 106 cfu/ml of rumen fluid (106), and c) 1 × 107 cfu/ml rumen fluid (107). Treatments were directly administered via rumen cannula once daily. Cows were fitted with pH probes in their cannula and connected to dataloggers, which monitor pH hourly. The experimental period was 21 d: 7-d adjustment, 14-d for pH, and in situ measurements. Cows fed 105 were able to sustain a higher nadir pH than were cows fed 106 or 107 . Cows fed 105 had a higher digestion rate of high moisture ear corn (HMEC) dry matter. Corn silage digestion was higher for cows fed 105 and 106 compared with those receiving 107. There were no carryover effects of treatment associated with rumen pH when switching from one treatment regimen to the next. Results from this study demonstrate that incorporation of a specific level of DFM aids in reducing diurnal ruminal acidity.

Evaluation of an Indwelling Ruminal Probe Methodology and Effect of Grain Level on Diurnal pH Variation in Dairy Cattle

To evaluate a ruminal probe for recording diurnal variation in rumen pH, we fitted three ruminally fistulated cows with probes affixed to the inside of the cannula. Probes were connected to a data logger and readings were recorded hourly. The experiment was a Latin square design with cows fed three different diets: 50, 60, and 70% grain as a total mixed rations once daily. Feed offerings and refusals were recorded daily. The experimental period was 21 d. The first 6 d were for adaptation, followed by 5-d rotations through each of the diets. Daily probe readings were recorded at 4-, 6-, 8-, 12-, and 24-h intervals. At each interval, readings were recorded (precleaned), a sample of rumen fluid was taken, and pH was measured in the laboratory. As probes were removed from the rumen, probe ends were cleaned with 0.1 N HCl and reinserted into the rumen, and a reading was recorded (post-cleaned). No protective pH probe shields were used in this experiment. There were no differences between pre- and postcleaned pH readings across cows for all diets. Mean time under pH 5.0, 5.5, and 6.0 were 0.2, 2, and 7.2h, respectively. Diet affected length of time under a certain pH, only for readings under pH 6. Diurnal pH profiles were monophasic in nature. The degree of acidity increased after feeding and duration of nadir increased with increasing grain in the diet. Daily DMI increased but was highly variable within the first week after switching to the next higher grain level. These results indicate the use of an indwelling ruminal probe without a protective shield, cleaned, and calibrated daily can accurately measure diurnal variation of ruminal pH. In addition, transition to higher grain levels in the diet increases pH, duration of pH nadir, and daily DMI fluctuation.

Esophagopharyngeal acid regurgitation: Dual pH monitoring criteria for its detection and insights into mechanisms

Background & Aims: A valid technique for the detection of esophagopharyngeal acid regurgitation would be valuable to evaluate suspected reflux-related otolaryngologic and respiratory disorders. The aim of this study was to derive pH criteria that optimally define esophagopharyngeal acid regurgitation and to examine patterns of regurgitation. Methods: In 19 healthy controls and 15 patients with suspected regurgitation, dual or quadruple pH sensors were used to monitor pharyngeal and esophageal pH. For each combination of the 2 variables, ΔpH and nadir pH, proportions of pH decreases that occurred during or independent of esophageal acidification were calculated to determine the likelihood that an individual pharyngeal pH decrease was a candidate regurgitation event or a definite artifact. Results: Overall, 92% of pharyngeal pH decreases of 1–2 pH units and 66% of pH decreases of this magnitude reaching a nadir pH of <4 were artifactual. Optimal criteria defining a pharyngeal acid regurgitation event were a pH decrease that occurred during esophageal acidification, had a ΔpH of >2 units, and reached a nadir of <4 units in less than 30 seconds. Regurgitation occurred more frequently in subjects in an upright (32 of 35) than in a supine (3 of 35 events; P ≤ 0.0001) position and was more frequently abrupt (synchronous with esophageal acidification) than delayed ( P ≤ 0.05). Conclusions: Accepted criteria for gastroesophageal reflux are not applicable to the detection of esophagopharyngeal acid regurgitation, and most regurgitation occurs abruptly and in upright position. GASTROENTEROLOGY 1999;117:1051-1061

Chelerythrine increases Na-K-ATPase activity and limits ischemic injury in isolated rat hearts.

Myocardial ischemia results in an increase in intracellular sodium concentration ([Na]i), which may lead to cellular injury via cellular swelling and calcium overload. Because protein kinase C (PKC) has been shown to reduce Na-K-ATPase activity, we postulated that pharmacological inhibition of PKC would directly increase Na-K-ATPase activity, reduce [Na]i during ischemia, and provide protection from ischemic injury. Isolated rat hearts were subjected to 30 min of global ischemia with and without the specific PKC inhibitor chelerythrine. Intracellular pH, ATP, and [Na]i were assessed using 31P and 23Na NMR spectroscopy, whereas Na-K-ATPase and PKC activity were determined using biochemical assays. Na/H exchanger activity was determined using the ammonium prepulse technique under nonischemic conditions. Chelerythrine increased Na-K-ATPase activity (13.76 +/- 0.89 vs. 10.89 +/- 0.80 mg ADP. h(-1). mg protein(-1); P = 0.01), reduced PKC activity in both the membrane and cytosolic fractions (39% and 28% of control, respectively), and reduced creatine kinase release on reperfusion (48 +/- 5 IU/g dry wt vs. 689 +/- 63 IU/g dry wt; P = 0.008). The rise in [Na](i) during ischemia was significantly reduced in hearts treated with chelerythrine (peak [Na](i) chelerythrine: 21.5 +/- 1.2 mM; control: 31.9 +/- 1.2 mM; P < 0.0001), without an effect on either acidosis (nadir pH 6.16 +/- 0.05 for chelerythrine vs. 6.08 +/- 0.04 for control), the rate of ATP depletion or Na/H exchanger activity. These data support the hypothesis that pharmacological inhibition of PKC before ischemia induces cardioprotection by reducing intracellular sodium overload via an increase in Na-K-ATPase activity.

Different effect of cold storage and rewarming on three pH regulating transporters in isolated rat hepatocytes.

Disturbances in hepatic pH homeostasis are thought to participate in the functional damage to liver grafts caused by the cold preservation and warm reperfusion necessitated by transplantation surgery. We have used an in vitro model of isolated rat hepatocytes suspended in cold University of Wisconsin (UW) solution and subsequently cultured at 37 degrees C to evaluate liver cell pH regulatory mechanisms after cold preservation and rewarming. Cells were kept for up to 72 h in cold UW solution, and at 24-h intervals intracellular pH (pHi) was measured after 60-90 min of warm culture by cytofluorometry using the fluorochrome 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein. When challenged with an alkaline load by isohydric HCO(3)(-)-CO(2) steps, hepatocytes exhibited similar maximal pH(i) values and recovered at the same rate, irrespective of cold storage time, indicating that Cl-/HCO(3)- exchange activity is quite resistant to hypothermic storage and subsequent rewarming. In parallel studies, cells were subjected to an acid load by the NH4Cl pulse technique in bicarbonate buffer containing 50 microM ethylisopropylamiloride to block Na+/H+ exchange. Despite similar nadir pH(i) (lowest pH(i) values due to acid load), the subsequent pH(i) recovery rate that reflects Na+-(HCO(3)-)n cotransport activity was increased significantly after hypothermic preservation. Hepatocytes were also perfused with a bicarbonate-free N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid buffer, and Na+/H+ exchange activity was evaluated using the same acid load protocol. Although cells always exhibited similar steady-state initial pH(i) and nadir, the rate of pH(i) recovery decreased significantly as a function of cold storage time in UW solution. Finally, intracellular buffering capacity was calculated from the sudden pH(i) changes induced by HCO(3)(-)-CO(2) steps or NH4Cl pulses and was found to remain stable throughout the 72 h of cold preservation. Therefore, the results strongly suggest that cold preservation and rewarming disturb hepatocellular pH regulatory mechanisms by attenuating Na+/H+ exchange and increasing Na+-(HCO(3)-)n cotransport, whereas Cl-/HCO(3)- exchange is not affected.

Chronic Extracellular Acidosis Induces Plasmalemmal Vacuolar Type H+ ATPase Activity in Osteoclasts

Proton extrusion into an extracellular resorption compartment is an essential component of bone degradation by osteoclasts. Chronic metabolic acidosis is known to induce negative calcium balance and bone loss by stimulating osteoclastic bone resorption, but the underlying mechanism is not known. The present studies were undertaken to evaluate whether chronic acidosis affects proton extrusion mechanisms in osteoclasts cultured on glass coverslips. Acidosis, mimicked experimentally by maintaining the cells at extracellular pH 6.5, rapidly lowered intracellular pH to 6.8. However, after 2 hours, a proportion of cells demonstrated the capacity to restore intracellular pH to near normal levels. To define the mechanism responsible for this recovery, the activity of individual H+ transport pathways was analyzed. We found that chronic acid treatment for up to 6 h did not significantly affect the cellular buffering power or Na+/H+ antiport activity. In contrast, chronic acidosis activated vacuolar H+ pumps in the osteoclasts. Although only approximately 5% of the control cells displayed proton pump activity, about 40% of cells kept at extracellular pH 6. 5 for 4-6 h were able to recover from the acute acid load by means of bafilomycin A1-sensitive proton extrusion. Conversely, the H+-selective conductance recently described in the plasma membrane of osteoclasts was clearly inhibited in the cells exposed to chronic acidosis. Following acid treatment, the activation threshold of the H+ conductance was shifted to more positive potentials, and the current density was significantly reduced. Considered together, these results suggest that induction of plasmalemmal vacuolar type ATPase activity by chronic acidosis, generated either systemically due to metabolic disease or locally at sites of inflammation, is likely to stimulate osteoclastic bone resorption and thus to promote bone loss.

Prolonged diving and recovery in the freshwater turtle, Pseudemys scripta—III. The effect of acidosis on lactate generation and O 2 consumption in brain slices

1. 1. The effect of progressive extracellular acidosis on the rate of lactate generation ( Q lactate) and O 2 consumption ( Q O 2 ) was studied in brain slices obtained from the freshwater turtle Pseudemys scripta elegans. 2. 2. At the nadir pH found in vivo during diving, Q lactate is 60% of the value found at pH 7.5 and at an extracellular pH 6.0, the value is 37% of the value at pH 7.5. These findings suggest that ATP supply derived from glycolysis decreases progressively during prolonged diving and that bioenergetic failure is an important factor during this process. 3. 3. Total brain Q o 2 does not change significantly over a range pH 6.0–7.5, averaging 2.3 ± 0.35μM × 100 g tissue −1 × hr −1. This suggests that the failure to repay the apparent O 2 deficit accrued during prolonged diving is not pH mediated.