LOWER ESOPHAGEAL SPHINCTER PRESSURE MEASUREMENT UNDER STANDARDIZED INSPIRATORY MANEUVEURS

Background: Through rhythmic variations, the diaphragm influence lower esophageal sphincter (LES) pressure acting as an external sphincter. LES pressure recording is characterized by increased pressure in inspiration due to contraction of the diaphragmatic crura that involves the sphincter. Aim: To describe a method of measuring LES pressure during standardized inspiratory maneuvers with increasing loads. Methods: The study population comprised of eight healthy female volunteers (average age of 31.5 years). An esophageal high-resolution manometry and impedance system was used for measuring the LES pressure during 3-second inspiratory efforts under 12, 24 and 48 cm H2O loads (Threshold maneuvers). Results: There was a significant difference between the average maximum LES pressure and the average maximum basal LES pressure during the first (76.19±17.92 difference, p=0.0008), second (86.92±19.01 difference, p=0.0004), and third seconds of the maneuver (90.86±17.93 difference, p=0.0002), with 12, 24 and 48 cmH2O loads. Conclusion: This maneuver is a standardization of the inspiratory LES pressure and may better differentiate patients with reflux disease from healthy individuals, and may also be useful for monitoring the treatment of these patients through inspiratory muscle training.


INTRODUCTION
T he lower esophageal sphincter is a 2-4 cm high pressure zone with intraabdominal and intra-thoracic segments. The pressure inversion point separates the lower esophageal sphincter (LES) segments and the intra-thoracic yields a negative pressure during inhalation. This segment is approximately 0.5 cm long, generally located in the middle of the high pressure zone, and related to the crural diaphragm. The LES normally extends two to four centimeters distal to the inversion point and corresponds to the intra-abdominal segment. The high pressure zone is asymmetrical with the left lateral and posterior pressures significantly higher 7 .
The diaphragm influences rhythmically the LES pressure, acting as an external sphincter. Its manometric profile is represented by an increase in pressure during inhalation, due to the contraction of the diaphragm that skirts the esophagus 7 .
There is evidence that the inspiratory pressure better distinguishes reflux esophagitis patients from controls 8 . Some patients with esophagitis may not increase inspiratory LES pressure during inhalation as much as controls 8 and some adaption may occur in other conditions 9 . The diaphragm contraction squeezes and lowers the gastroesophageal junction during inspiration.
The topographic profiles of the gastroesophageal juntion delivered by high resolution manometry (HRM) shows both its pressure and lowering. The aims of this study was to describe a measurement method of the LES pressure during standardized inspiratory maneuvers with stepwise increasing efforts.

Volunteers
Eight healthy volunteers (without GERD symptoms) were submitted to HRM of the esophagus in the Gastroenterology Research Laboratory of the Clinical Medicine Department of the Ceará Federal University (Fortaleza, CE, Brazil). The study was a qualitative and quantitative in humans. The ethical principles concerning human research set by the 196/96 resolution of National Health Council was followed.

Manometry
HRM is a standard method of measuring the pressure gradient across the gastroesophageal junction and its relaxation, allowing accurate diagnosis of diseases associated with hyper or hypotonicity. It also allows the localization of the LES upper border which is necessary for pH monitoring probe positioning 4 .
HRM was performed with volunteers in the supine position and after at least 6 h fasting. The probe had 36 pressure 1 cm apart and 18 impedance sensors 2 cm apart (Given Imaging, Yokneam, Israel). Pressure calibration was performed at 0 and 300 mmHg and zeroed to atmospheric pressure before the procedure. The probe was positioned through one nostril with at least five sensors distal to the diaphragm. The protocol included a basal period, six 5-ml saline swallows and a respiratory maneuver 2 .

Inspiratory maneuver
The respiratory maneuver has been previously descried 2 . The volunteers stayed at the supine position without swallowing and the LES pressure was measured for 20 seconds before and during the maneuver. The maneuver consisted of fast and forced inhalation through a membrane valve (Threshold IMT, Philips Respironics, Andover, MA, USA) whose closing pressure (cmH 2 O) could be adjusted by a compression spring (Figure 1  The following variables were measure with the ManoView Analysis Software 3.0, with 20 mmHg isobaric pressure. The average basal pressure (mmHg) was the mean pressure of the "A" rectangle with the height defined by the proximal and distal borders of the LES and the length equal to six seconds.
The basal contractility integral (IC) was the product pressure x height x length of the "A" rectangle inside the 20 mmHg isobaric contour.
The minimal inspiratory oral pressure (mmHg) was the lowest hypopharyngeal pressure during the maneuver.
The minimal inspiratory esophageal pressure (mmHg) was the lowest esophageal pressure during the maneuver.
The LES lowering was figured out on the "B" rectangle, defined by two angles, first, the right angle formed by the horizontal line passing through the upper border of the LES and the vertical line at the start of the maneuver. The second angle was formed by a vertical line at a "t" time and the LES distal border at time t. The LES lowering (ds) was the height of the rectangle B (cm).
The maximal LES pressure (mmHg) was the highest pressure in rectangle B at each time t.
The LES contractility integral (CI) was the product pressure x height x length of the "B" rectangle inside the 20 mmHg isobaric contour at each time t. Groups of similar variables were tested for distribution with the Student t test at a significance cutoff of 0.05.

RESULTS
Eight female healthy volunteers aged 31. 5 Figure 3 shows the increase in LES pressure across the three loads of the maneuvers.  The crural diaphragm contractions are also related to shifts in gastroesophageal junction pressure. Generally, these contractions are associated with respiration. There is a 10 to 20 mmHg increase in pressure during normal inhalation, and 50 to 150 mmHg during deep inspiration 5 . The Threshold device is used to strengthen the inspiratory muscles. It is made by one-way diaphragm valve kept in place by a spring which compression can be adjusted manually. Therefore, the inspiratory effort necessary to displace the membrane and allow airflow can be increased linearly. Inspiratory muscles are trained this way 3,10 . There is no effort during exhalation.
This inspiratory maneuver has been adapted to HRM in order to measure the gastroesophageal junction inspiratory pressure in GERD 8,9 . During the 12 cmH 2 O maneuver, there was a stepwise increase in the maximal inspiratory LES pressure, relative to the maximal basal pressure -2.23 times at the first second, 2.41 times at the second second, and 2.47 times at the third second. These relative increments were 2.09 times at the first second, 2.3 times at the second second, and 1.94 times at the third second for the 24 cmH 2 O maneuver, and 2.41 times at the first second, 2.49 times at the second second, and 2.66 times at the third second for the 48 cmH 2 O maneuver ( Table 3).
The inspiratory maneuver depends on volunteer effort and collaboration. This is a weakness of this method as can be seen by the large variation of the maximal inspiratory LES pressure values. The relatively lower increase in the maximal pressure during the third second of the 24 cmH 2 O maneuver could have occurred because of this drawback. On the other hand, the stepwise increase in LES pressure across the 1, 2, and 3 seconds of maneuver is a strong-point of the method. This attribute may help differentiate distinct pathological conditions.

CONCLUSION
This maneuver is a standardization of the LES inspiratory pressure measurement. It may better differentiate GERD patients from healthy individuals, since the former ones may have a crural deficiency and a lower inspiratory LES pressure. Furthermore, this maneuver may help monitor the efficiency of inspiratory muscle training for GERD 8 .