Digestive D&eases and Sciences, Vol. 37, No. 8 (August 1992), pp. 1200-1205

Effect of Cold Stress on Postprandial Lower Esophageal Sphincter Competence and Gastroesophageal Reflux in Healthy Subjects R. PENAGINI, B. BARTESAGHI, and P.A. BIANCHI

The effect o f cold stress on postprandial lower esophageal sphincter competence and gastroesophageal reflux was investigated in nine healthy subjects. All subjects were studied twice in a randomized order according to a common protocol: 30 rain after completion o f a 700-kcal meal they put their nondominant hand in water either at 37 ~ C (control stimulus) or at 4 ~ C (stressful stimulus) cyclically for 20 min. Pulse rate and blood pressure rose significantly (P < 0.01) during the stressful stimulus, but remained unaffected by the control stimulus, Rate o f transient lower esophageal sphincter relaxations~30 min [median (interquartile range)] was similar before and during control stimulus, 4 (2.7-5.0) and 3 (2.0--4.5), respectively, whereas it was markedly inhibited during the stressful stimulus [from 5 (3.7-6.0) to 2 (1.0-2.0); P < 0.05 vs control stimulus]. Rate o f reflux episodes~30 min was also similar before and during control stimulus, 1 (0-1.2) and 1 (1.0-2.2), but fell consistently during the stressful stimulus [from 2 (0-3.2) to 1 (0-2.0); P < 0.05 vs control stimulus]. Percentage o f transient lower esophageal sphincter relaxations accompanied by a reflux episode was unaffected by stress as was basal lower esophageal sphincterpressure. It is concluded that cold stress decreases the postprandial rate o f transient lower esophageal sphincter relaxations and reflux episodes in healthy humans. KEY WORDS: esophageal function; esophagus; gastroesophageal reflux; stress.

Stress is known to affect gastrointestinal motility at various sites (1-5). Recently, stressful stimuli have been shown to increase basal upper esophageal sphincter pressure (6), amplitude, and velocity of esophageal peristalsis (7). However, whether stress also influences lower esophageal sphincter motor function has still to be explored. The aim of our study was to evaluate the effect of cold stress on postprandial variables of lower esophageal sphincter competence, namely transient lower esophageal sphincter relaxations (TLESRs) Manuscript received July 23, 1991; revised manuscript received January 29, 1992; accepted February 7, 1992. From the Cattedra di Patologia Medica III, Istituto di Scienze Mediche, University of Milan, Milan, Italy. Address for reprint requests: R. Penagini, Cattedra di Patologia Medica III, Pad. Granelli, Via F Sforza, 35 20122 Milan, Italy.

1200

and basal lower esophageal sphincter pressure, and gastroesophageal reflux in healthy subjects. The postprandial period was chosen as it is the time of the day when most reflux events occur (8, 9).

MATERIALS AND METHODS Subjects. Eleven healthy subjects (ages 19-24 years; eight men) with no symptoms or past history of gastrointestinal disease were enrolled in the study, which was approved by the Human Research Review Committee of the Ospedale Maggiore of Milan. Two subjects were excluded from analysis because technical problems prevented adequate analysis of the recordings for the occurrence of TLESRs, ie, excessive rate of swallowing in one subject and an unclear swallow signal in the other one. Manometric and oH Recording Technique. Esophageal motility was monitored using an assembly of polyvinyl tubes incorporating a sleeve sensor (Dentsleeve, Belair, Digestive Diseases and Sciences, Vol. 37, No. 8 (August 1992)

0163-2116/92/0800-1200506.50/09 1992PlenumPublishingCorporation

STRESS, TLESRs, AND GASTROESOPHAGEAL REFLUX C ~ (water ST*C) MEAL f-3 TIME (min)

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Fig 1. Experimental protocol used in all studies. Each subject underwent a control experiment (water 37~ C) and a stress experiment (water 4~ C). *Repeated 1-min immersions of the nondominant hand in water with intervening rest periods of 15 sec. Australia). The 6-cm-long sleeve was positioned so that it straddled the lower esophageal sphincter. A side hole 1 cm below the distal margin of the sleeve recorded intragastric pressure. Side holes at the upper margin of the sleeve and 5 and 10 cm more proximally monitored motor activity of the esophageal body at levels 2, 7, and 12 cm above the lower esophageal sphincter. One of two side holes at 23 and 28 cm proximal to the upper margin of the sleeve monitored swallows in the pharynx. Each lumen was connected to a pressure transducer (Sensormedics 223651) and perfused with distilled water by a low-compliance pneumohydraulic infusion pump (Sensormedics, Milan, Italy; response: >200 mm Hg/sec at 0.5 ml/min) except for the pharyngeal port, which was water filled, but not perfused to avoid stimulation of swallowing. The gastric side hole and sleeve were perfused at 0.5 ml/min, whereas the side holes in the esophageal body were perfused at 0.13 ml/min in order to minimize the fluid load to the subject. Intraesophageal pH was monitored using a Beckman unipolar intraluminal pH electrode (model 39043) positioned 5 cm above the proximal margin of the lower esophageal sphincter. Signals from the pressure transducers and pH electrode were processed and recorded on a polygraph (Sensormedics, Anaheim, USA, model R711) at a paper speed of 1 mm/sec. Conduct of Experiments. The subjects underwent two 90-min postprandial experiments (control and stress) in a randomized order and on two separate days, according to the same protocol, as shown in Figure 1. After an overnight fast, the subjects swallowed the assembly of polyvinyl tubes and the pH electrode. They rested for 30 min to accommodate to the presence of the intraluminal assembly and then they ate a meal consisting of 400 ml of a commercially available diet formula (Ensure Plus, Nutricia, Italy) with four slices (34 g) of crispbread (Wasa GmbH, Germany) containing 5 g of dietary fiber. The slices had been previously homogenized with the liquid component of the meal. The final meal had a porridge consistency, a total volume of 500 ml, and a caloric content of 700 kcal (56% carbohydrates, 27% lipids, 17% proteins). When 30 min from the meal had elapsed, the subjects underwent repeated 1-min immersions of their nondominant hand in water either at 37~ C (control experiment) or 4~ C (stress experiment), with intervening rest periods of 15 sec for 20 min. Esophageal motility and intraesophageal pH were recorded for 90 min after cornDigestive Diseases and Sciences, Vol. 37, No. 8 (August 1992)

pletion of the meal. Serial measurements of brachial arterial blood pressure using a sphygmomanometer and radial artery pulse rate were performed throughout the experiments. The subjects remained supine, except while eating their meal, to prevent any influence of posture on the rate of TLESRs (10, 11). Analysis of Records. The experiments were divided in three 30-min epochs for analysis (0-30, 30-60, 60-90). Although the hand immersion procedure lasted 20 min only (30-50 min after the meal), the subjects were considered to be under stress from 30 to 60 min as hand discomfort and autonomic stimulation have been shown to last for at least l0 min after the end of the immersions (1, 3). Mean end-expiratory basal lower esophageal sphincter pressure of each 30-min epoch, referenced to endexpiratory intragastric pressure, was derived by averaging 1-min visual means of the tracing. Swallow-induced relaxations and contractions, TLESRs, and artifacts were disregarded in the analysis. On average, 23 one-minute measurements were made in each subject in each of the three epochs. TLESRs were defined as abrupt falls in lower esophageal sphincter pressure to --1 pH unit. All the cardiovascular and gastrointestinal variables were analyzed for differences among the three epochs within each experiment. Furthermore, rates of TLESRs, rates of reflux episodes, and percentage of TLESRs accompanied by a reflux episode during epoch 30-60 (stimulus) were also compared in the control and stress experiment. For this purpose, the variables were considered only after subtraction of the respective value before stimulation (ie, during epoch 0-30), as they were expected to vary spontaneously from one day to the other in the same subject, and they were called ATLESRs, ARE, and A%RE respectively. Statistics. Statistical significance of differences among the three epochs within each experiment was tested using parametric or nonparametric analysis of variance, according to data distribution. Differences in ATLESRs, ARE, and A%RE between control and stress experiments were assessed by the Wilcoxon test. Cardiovascular variables and lower esophageal sphincter pressure were expressed as mean - SD and the remaining variables as median (interquartile range). RESULTS All subjects felt that cold-water immersion was an unpleasant stimulus; nevertheless, they were all able

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PENAGINI

TABLE I. CARDIOVASCULARVARIABLES DURING CONTROL (C) AND STRESS (S) EXPERIMENTS (MEAN + SD)

Epoch Variables Pulse rate (beats/min) C S Systolic BP* (ram Hg) C S Diastolic BP ( m m Hg) C S

0-30 rain

30-60 min (stimulus)

60-90 min

71-+ 12 75 - 14

71 - 12 79 - 14t

7 0 - 12 73 -+ 11

121 -+ 13 124 - 12

122 --+ 14 137 - 13I"

120 + 12 124 -+ 10

76-+5 75-6

75-6 86-8t

75-6 75-+6

*BP = blood pressure. ?P < 0.01 vs 0-30 and 60-90 min.

to complete the 20 min stimulation period. No subject felt warm water immersion as unpleasant. Rate of

ET AL

spontaneous swallows/30 min was 35 +- 17 and 37 -+ 16 during control and stressful stimuli, respectively. Cardiovascular Variables. Cardiovascular variables are summarized in Table 1. In the control experiment, pulse rate and systolic and diastolic blood pressure were the same during the three epochs. In the stress experiment, all three variables rose significantly (P < 0.01) during hand immersion in cold water (epoch 30-60 min), and returned to basal values in epoch 60-90. Lower Esophageal Sphincter Pressure. Basal lower esophageal sphincter pressure was unchanged during both experiments, the values being l0 -+ 5, l0 - 4, and 10 +- 5 mm Hg in control, and 9 +- 3, 9 -+ 4, and 9 +- 3 mm Hg in stress experiments for epochs 0-30, 30-60, and 60-90, respectively. Transient Lower Esophageal Sphincter Relaxations. A typical example of a TLESR accompanied by a

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Tracing f r o m a subject during a T L E S R a c c o m p a n i e d by a reflux episode. L E S = lower esophageal sphincter. T h e horizontal broken line indicates intragastric p r e s s u r e a n d the vertical one o n s e t of reflux.

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Digestive Diseases and Sciences, Vol. 37, No. 8 (August 1992)

STRESS, TLESRs, AND GASTROESOPHAGEAL REFLUX CONTROL

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