Lower esophageal sphincter pressure in Chagas\' disease

Digestive Diseases and Sciences, Vol. 35, No. 4 (April 1990), pp. 508-512

Lower Esophageal Sphincter Pressure in Chagas' Disease ROBERTO O. DANTAS, MD, RENATO A. GODOY, MD, RICARDO B. OLIVEIRA, MD, ULYSSES G. M E N E G H E L L I , MD, and LUIZ E.A. TRONCON, MD

It is known that lower esophageal sphincter (LES) pressure in patients with idiopathic achalasia is higher than in normal subjects, but in patients with Chagas' disease, who have esophageal disease with similar clinical, manometric, and radiologic results, studies of LES pressure show contradictory findings. We measured the LES pressure in 118 patients with chronic Chagas' disease, 14 patients with idiopathic achalasia, and 50 control subjects using a perfused catheter and the stationary pull-through (SPT) technique. The patients with Chagas' disease had normal esophageal radiologic examination (group A, N = 50), delay in esophageal clearance without dilatation (group B, N = 41), or delay in esophageal clearance with dilatation (group C, N = 27). The LES pressure of Chagas' disease patients of group A (18.6 + 9.1 mm Hg, mean +- SD), group B (17.8 +9.7 mm Hg), and group C (21.6 +- 10.1 mm Hg) was lower (P < 0.001) than the LES pressure of the controls (24.9 +- 10.2 mm Hg). In patients with idiopathic achalasia, the LES pressure (40.7 +_ 17.8 mm Hg) was higher than in control subjects (P < 0.01) and Chagas' disease patients (P < 0.001). We conclude that the LES pressure of patients with Chagas' disease tended to be lower than that of control subjects and achalasia patients. KEY WORDS: Chagas' disease; achalasia; lower esophageal sphincter; esophagus.

Chagas' disease is the result of infection with the hemoflagellate protozoan Trypanosoma cruzi, the consequence of which, for the digestive tract, is destruction of the intramural neurons (1, 2). In the esophagus, the motor disorder resulting from denervation is characterized by aperistalsis in the esophageal body and incomplete relaxation of the lower esophageal sphincter (LES) in response to swallowing (3).

Manuscript received August 21, 1989; revised manuscript received January 11, 1990; accepted January 15, 1990. From the Departamento de Clfnica M6dica, Faculdade de Medicina de Ribeir~o Preto, Universidade de S~o Paulo 14049, Ribeir~o Preto, S~o Paulo, Brazil. Presented in part at the 8th World Congress of Gastroenterology, September 1986, S~o Paulo, Brazil, and published in abstract form in Dig Dis Sci 31:273, 1986. Address for reprint requests: Dr. Roberto O. Dantas, Departamento de Clfnica M6dica, Faculdade de Medicina de Ribeir~o Preto, USP, 14049, Ribeir~o Preto, SP, Brazil.

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Although there is some similarity in pathology, clinical manifestations, and esophageal radiologic and manometric examination between patients with idiopathic achalasia (4) and Chagas' megaesophagus (2, 3), it is possible that the denervation is not of the same kind in the two diseases (5). It is suggested that in achalasia, the denervation mainly involves inhibitory neurons (6), with normal or only slightly compromised excitatory cholinergic innervation (7). In Chagas' disease, there is some evidence that the denervation affects both the inhibitory (8) and cholinergic excitatory neurons (9). If this difference is correct, we can anticipate that the resting LES pressure, which is elevated in achalasia (7, 10), may be normal or low in Chagas' disease. The aim of this study was to compare resting LES pressure in patients with Chagas' disease, in patients with idiopathic achalasia, and in control subjects. Digestive Diseases and Sciences, Vol. 35, No. 4 (April 1990)

0163-2116/90/0400-0508506.00/09 1990PlenumPublishingCorporation

LES PRESSURE IN CHAGAS' DISEASE MATERIALS AND METHODS Patients. We recorded the LES pressure of 118 patients with chronic Chagas' disease, 14 patients with idiopathic achalasia, and 50 control subjects, all of whom denied previous esophageal treatment. The study was conducted according to the terms of the Helsinki Declaration. Informed consent was obtained from each subject. The controls (27 men and 23 women) were 14-69 years old (mean -+ SD: 37 --+ 14 years). All the control subjects were free from cardiac or digestive disease, and their esophageal manometric examination was normal. All of them had negative serologic reactions for Chagas' disease (immunofluorescence and/or complement fixation). The frequency of wet swallows followed by complete LES relaxation was 100%, and the frequency of wet swallows followed by peristaltic contractions was 96%. Contraction amplitude 5 cm above the LES was 100 - 50 mm Hg (mean - sD). The patients with achalasia had negative serologic reactions for Chagas' disease, and clinical or laboratory work-up showed no evidence of cardiac or colon disease. There were six men and eight women referred for investigation and treatment of dysphagia, ages 16-46 years (mean 26 --- 9 years). Radiologic examination demonstrated absent peristalsis in thoracic esophagus, delay in esophageal clearance without dilatation (N = 2) or with dilatation (N = 12). Manometry showed absent peristalsis in the esophageal body and abnormal LES relaxation in response to wet swallows, and endoscopy showed no evidence of tumors at the esophagogastric junction. The diagnosis of Chagas' disease was based on a positive serologic reaction and clinical manifestations of the disease in the esophagus, colon, or heart (2, 3). The patients were 65 men and 53 women ages 11-71 years (mean 45 -+ 13 years). Patients were classified into three groups by esophageal radiologic examination performed in an upright position. Group A patients had normal transit of contrast (N = 50), group B had delayed esophageal clearance without dilatation (N = 41), and group C had dilatation and delay in esophageal clearance (N = 27). Dysphagia was a symptom in 72% of cases and, on manometry, the frequency of wet swallows followed by incomplete LES relaxation was 82% and the frequency of wet swallows followed by aperistaltic contraction was 20% for group A, 71% for group B, and 100% for group C. Contraction amplitude 5 cm above the LES was 57 -+ 40 mm Hg. The patients without clinical, manometric, or radiologic esophageal manifestations of the disease (N = 20) had megacolon or cardiopathy.

LES Pressure Measurement. We used a four-lumen polyvinyl manometric catheter 5 mm in outer diameter and 1 mm in inner diameter. The lumens opened with side holes of 1 mm and a radial orientation spaced at 20, 18, 15, and 10 cm from the distal end of the catheter. Immediately distal to the side holes, each lumen was plugged with a radiopaque marker. The catheter was connected to pressure transducers (Elema-Siemens AB) with output displayed on an eight-channel recorder (Mingograph 804 Siemens). The catheter was infused with water at 1.7 ml/min through each lumen using a pneumohydraulic infusion system. The pressure rise rate of the system was 250 mm Hg/sec. The LES pressure was measured by a station pullthrough (SPT) technique. Each subject was studied in the supine position following at least 6 hr of fasting. The manometric assembly was passed via the nose until the four radiopaque markers were radiologically shown to be inside the stomach. After 10 min of stabilization, the catheter was pulled in l-cm increments every 30 sec. The highest pressure measured at end-expiration by one of the side holes represented the LES pressure for each subject. The end-expiratory intragastric pressure (ram Hg) was measured as reference. Statistical Methods. The statistical evaluation was done by analysis of variance (one-way ANOVA), and by the unpaired Student's t test. The data are reported as X -+ SD.

RESULTS

Mean L E S pressure was lower in Chagas' disease patients than in the control subjects (P < 0.001) and was higher in achalasia patients than in the controls (P < 0.01) and in Chagas' disease (P < 0.001). There was no difference in L E S pressure among the three groups of Chagas' patients (Table 1). The distribution of individual pressure values showed considerable overlap between controls and patients (Figure 1). The pressure was above 35 mm Hg (~" + sD o f controls) in 10% of control subjects, 5% of Chagas' patients, and 57% of achalasia patients, and was under 15 m m Hg (X - so of controls) in 10% o f controls, 39% of Chagas' patients, and none of the achalasia patients. Only patients with Chagas' disease (13%) had pressures below 10 mm Hg.

TABLE 1. LOWER ESOPHAGEALSPHINCTERPRESSURE (MM HG)* Chagas' disease

Mean SD Median

Controls (N = 50)

A (N = 50)

B (N = 41)

C (N = 27)

A chalasia (N = 14)

24.9 10.2 24.0

18.6a 9.1 16.9

17.8a 9.7 16.3

21.6 c 10.1 20.0

40.7 b'a 17.8 39.0

*A: normal radiological esophageal examination; B: delay in esophageal clearance without dilatation, C: delay in esophageal clearance with dilatation; ap < 0.001, bp < 0.01, cp < 0.05 compared with controls; ap < 0.001 compared with Chagas' disease. Digestive Diseases and Sciences, Vol. 35, No. 4 (April 1990)

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DANTAS ET AL

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ACHALASIA

Fig 1. Lower esophageal sphincter (LES) pressure of Chagas' disease patients with normal radiological esophageal examination (A), with delay in esophageal clearance without dilatation (B), with delay in esophageal clearance with dilatation (C), of patients with idiopathic achalasia and of controls. Horizontal bars and numbers show the respective means. *Significantly different (P < 0.001) from control and achalasia. Groups A, B, and C did not differ from one another (P > 0.05).

When we analyzed the subjects over and under 40 years old separately, the difference between controis, Chagas' patients (Table 2), and achalasia patients persisted. There was no difference in mean LES pressure between Chagas' disease patients with or without dysphagia (19.3 --+ 10.5 mm Hg and 18.3 --- 6.9 mm Hg, respectively), with predominance of peristaltic or aperistaltic contractions in the esophagus (19.7 -+ 10.1 and 18.5 --- 9.2 mm Hg) or the combination of peristalsis and no dysphagia or aperistalsis and dysphagia (18.9 --- 7.1 and 18.8 9.4 mm Hg). DISCUSSION Our results show that there is a difference in LES pressure between patients with idiopathic achalasia and with Chagas' disease. Although the esophageal motility disorder and symptoms are similar in the two conditions (2-4), the impairment of LES tonus control should be different (5).

Three mechanisms are involved in the genesis of LES pressure (11) and might be impaired by the diseases: excitatory neural stimulation, myogenic tone, and endogenous enteric hormones. The participation of each in the maintenance of resting LES pressure in fasting subjects is not totally clear. Enteric hormones may not contribute to the genesis of LES tonus in normal subjects (11, 12), and the cholinergic nerves are not responsible for the entire pressure value (13). A possible explanation for the higher LES pressure observed in achalasia patients than in Chagas' patients may be the different sensitivity to gastrin [hypersensitivity in achalasia (7, 10) and hyposensitivity in Chagas' disease (14)] and mainly the more important impairment of excitatory cholinergic innervation in Chagas' disease (9) than in achalasia (7). Since the myenteric plexus of the esophagus and of other organs are always involved in Chagas'

TABLE 2. AGE AND LOWER ESOPHAGEAL SPHINCTER (LES) PRESSURE*

Controls

40 years Total

Chagas' disease

Mean age (years)

Number o f subjects

LES pressure (ram Hg)

Mean age (years)

Number o f subjects

LES pressure (mm Hg)

26 -+ 6 51 -+- 7 37 --- 14

27 23 50

24.3 -+ 10.7 25.6 -+ 9.6 24.9 + 10.2

31 -+ 7 52 -+ 8 45 -+ 13

41 77 118

20.3 -+ 8.7 a 18.3 -+ 10.0b 19.0 -+ 9.6 ~

*Pressure and age: X -+ SD; ap < 0.05, bp < 0.005, cp < 0.001 compared with controls. 5 10

Digestive Diseases and Sciences, Vol. 35, No. 4 (April 1990)

LES PRESSURE IN CHAGAS' DISEASE

disease, even in the absence of clinical manifestations (2, 3), the lack of correlation between the LES tonus and the clinical, manometric, and radiologic esophageal examination is understandable. Other studies of LES pressure in Chagas' disease have obtained contradictory results. In some, the pressure was the same as in controls (15, 16), in others it was higher (17, 18), and in yet another it was lower (14). Different measuring techniques or numbers of patients may explain these differences. The LES pressure measured by the rapid pullthrough technique (RPT), which is easier to perform and more reproducible, is higher than the LES pressure measured by SPT (19). However, we do not know whether the LES response to RPT in Chagas' disease is the same as in control subjects, who have a spasm of the upper esophageal sphincter during the rapid movement of the catheter (20-22). The role of diaphragmatic contraction also may be important (23). Thus, it is suggested that SPT is better than RPT to measure LES pressure (24) and that SPT, at the end-expiratory phase, is the more accurate approximation of intrinsic LES tonus (25-27). The LES pressure we recorded in controls was close to values obtained in previous studies (7, 10, 19, 28). Pressures higher than 40 mm Hg can be observed in normal subjects (28, 29) and do not vary with sex or age (27). The pressure recorded here in achalasia patients was the same as observed in previous studies on larger series (7, 30). We conclude that the LES pressure of patients with Chagas' disease is lower than that of patients with idiopathic achalasia, suggesting that the impairment of the mechanisms of control of the LES tonus should be different in the two diseases. A complete explanation of these findings awaits further studies.

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