In order to evaluate the contribution of the myenteric plexuses to the control of gastric accommodation to distension and to the rate of gastric emptying of a saline solution in man, we have evaluated these functions in patients with Chagas' disease, which is known to be associated with extensive lesions of the myenteric plexuses. Intragastric pressure was significantly higher (P < 0.05) in Chagas patients (N = 15) than in normal controls (N = 15) for air distension volumes of 100-700 ml. In the range 300-700 ml, the difference between the groups was approximately twofold (P < 0.001). The gastric emptying rate of 500 ml 154 mM NaCl in a second group of Chagas' disease patients (N = 13) was significantly faster than that of the control group (N = 17) at 5 min (P < 0.005) and at 15 min (P < 0.005) after the test meal, but at 25 min the volumes remaining in the stomach were not statistically significant for the two groups (P > 0.10). The impairment of gastric accommodation to distension and consequent rapid gastric emptying demonstrated for chagasic patients emphasizes the role of the myenteric plexuses in gastric reservoir function in man and complements previous evidence obtained in animal studies.

Degeneration of the parasympathetic ganglia in the heart and in the smooth muscle (esophagus, colon, and bronchi) is known to occur in Chagas' disease. The reflex bradycardia associated with acute elevation in systemic arterial pressure and the blocking of this reflex effect with atropine are used in this investigation to study vagotonic influences on the heart in patients with Chagas' disease. Failure to increase heart rate following administration of atropine observed in cases of chronic Chagas' heart disease is believed to be a functional disorder related to degeneration of the neuronal supply to the sino-atrial region of the heart. To the authors' knowledge this report provides the first existing physiological investigation concerning the cardiovascular system in Chagas' disease.

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 less than 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 less than 0.01) and Chagas' disease patients (P less than 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.

In order to evaluate the effect of pentagastrin on the motor activity of the sigmoid and rectum in patients with Chagas’ disease, manometric studies were performed on 22 chagasic patients, 11 without and 11 with megacolon, and 11 control subjects. Pentagastrin had a stimulating effect on the sigmoid and rectum in control subjects as well as in chagasic patients without megacolon. In chagasic patients with megacolon, pentagastrin had no effect on sigmoid or rectum motility, probably as a result of the intrinsic denervation known to occur in this disease. The findings suggest that the motor effect of pentagastrin on the human sigmoid and rectum depends on the myenteric nervous pathways.

The fasting motor activity of the upper small intestine was studied in 36 patients with chronic Chagas' disease, which is known to be associated with extensive lesions of the myenteric plexuses, and the results compared with those obtained in 15 control subjects. The migrating motor complex (MMC) was detected as frequently in the Chagas' disease group as in the control group, and the frequency of contractions during the activity front was virtually the same in the two groups. In the Chagas' group the propagation of the activity fronts was slower, their duration was longer in the jejunum, but not in the duodenum, and the calculated length was shorter than normal. Chagas' disease patients without clinical manifestation or x-ray pathology of the digestive tract had no abnormalities of the MMC. These findings suggest that the intramural nervous system of the gut plays a role in the normal migration of the MMCs along the small intestine.

The Valsalva maneuver was performed by a series of eight patients with chronic Chagas' heart disease who had no current evidence nor past history of heart failure. The fact that all the patients showed recovery of arterial pressure during the latter portion of the period of increased airway pressure and exhibited significant overshoot in pressure in the post-straining period of the Valsalva maneuver strongly suggests that reflex activity of arteriolar tone was present. However, slowing of the heart rate was not found in association with the blood pressure overshoot in half of the patients. This abnormal response was observed only in patients in whom atropine sulfate failed to cause an increase in heart rate. These results are interpreted as a further indication of degeneration of autonomic nervous system controlling heart rate in chronic Chagas' heart disease. formerly of the Mayo Graduate School of Medicine and presently of the Medical School of the University of Minnesota, are hereby fully acknowledged, as is the Circulation, Volume XL, December 1969 884 by guest on March 29, 2015 http://circ.ahajournals.org/ Downloaded from

Gastric acid and pepsin secretory responses to graded doses of pentagastrin were measured in 12 Chagas’ disease patients and 18 control subjects, and in 7 Chagas’ disease patients and 6 controls the study was repeated with an infusion of bethanecol. Calculated maximal outputs of acid and pepsin (V_max) and responsiveness (D₅₀) of the acid- and pepsin-secreting cells to pentagastrin were lower in the chagasics. Bethanecol had no significant effect on pentagastrin-stimulated gastric secretions in controls. The impairment of responsiveness of the gastric secretory cells in Chagas’ disease patients was fully corrected by bethanecol.

SUMMARY Intraluminal manometric studies were performed in 14 chagasic patients with megaoesophagus, 10 chagasic patients with megacolon, and 15 control subjects. Basal lower oesophageal sphincter pressure was 20.27±1 16 mmHg (mean±SEM) in controls as compared with 15.16±1.53 mmHg in chagasics with megaoesophagus and 14.38±1.50 mmHg in chagasics with megacolon. Dose-response studies to intravenous pentagastrin showed that the chagasic patients exhibited a lower sensitivity to the stimulant than did the controls, as demonstrated by shifting of the doseresponse curve to the right and higher individual values of the dose for half maximal contraction (D50). No difference was noted between the calculated maximal contraction (Vmax) of oesophageal sphincter of controls and chagasics. These data are compatible with the hypothesis of an interaction between pentagastrin and cholinergic nervous excitation on oesophageal sphincteric smooth muscle.