April 1995 Motility and Nerve-Gut Interactions A707

• AUTONOMIC NEUROPATHY IN ACHALASIA: POSTPRANDIAL DECREASE OF PULSATILITY INDEX (PI) IS AUGMENTED AND INCREASE OF BLOOD VELOCITY IS IMPAIRED IN SUPERIOR MESENTERIC ARTERY. A. yon Herbay, T. Heyer, P. Auer, H.J. L0bke, D. H/iussinger, T. Frieling. Dept. of Gastroenterology, Heinrich-Heine- University of D0sseldorf, Germany. It has been suggested that achalasia is associated with extraesophageal sympathetic and parasympathetic dysfunction (P. Auer, el al., Gastroenterology 106:A461. 1993; V.F. Eckardt, el al. Gastroenterology 106:492, 1993). Methods: In a prospective study, we investigated basal and postprandial gall bladder volume, velocity and pulsatility index (PI) of superior mesentedc artery and portal vein in 9 patients with achalasia of the esophagus (5 men) and 10 healthy controls (4 men). Gall bladder volume was measured by ultrasound (Toshiba SSH 140A, sonolayer alpha), velocity and PI of superior mesenteric artery and portal vein by duplex sonography. In each measurement, velocity was corrected by evaluation of the doppler angle. Triple measurements were obtained at basal state, 15, 30, 60 and 90 minutes postprandially. The meal consisted of 300ml liquid formula diet (Fresubin, 300 kcal, 11,4g protein, 10.2g lipid, 41.4g carbohydrate). Results: At basal state, gall bladder volume, velocity and PI were not significantly different between both groups. Gall bladder volumes significantly decreased (p<0.05, students t- test) and blood velocity in portal vein significantly increased 15, 30, 60 and 90 minutes poslprandially in achalasia and controls. However, no significant differences occurred between both groups. In contrast. signifcant differences between both groups (PI: 15' and 30'; velocity: 15', 30'. 60' and 90') were found according to postprandial decrease of PI and increase of blood velocity in superior mesenteric artery (p<0.01 and p<0.O5). Postprandial decrease of PI compared to basal state was 30 + 4 % (15'), 24 + 5 % (30'), 21 + 5 % (60') and 18 + 5 % (90') in controls and 48 _+ 3 % (15'), 47+ 4 % (30'), 27 + 6 % (60') and 22 + 5 % (90') in achalasia (mean + SEM). Increase of postprandial velocity was 75 + 17% (15'), 57 _+ 13% (30'), 31 + 5 % (60') and 25 + 9 % (90') in controls and 25_+7%(15'), 19_+6%(30% 6 + 5 % ( 6 0 ' ) a n d - l + 3 % ( 9 0 ' ) i n achalasia. Conclusion: These data suggest altered autonomous regulation of superior mesenteric artery in patients with achalasia. The study provides further evidence for generalized,autonomic neuropathy in achalasia that extends beyond the esophagus. (supported by DFG Grant Fr 733/3-2).

1,4,5-1NOSITOLTRISPHOSPHATE MEDIATES CARBACHOL- INDUCED CONTRACTION OF GALLBLADDER SMOOTH MUSCLE. T. von Schrenck, U. Matsui, A. de Weerth, P. Lossin, S. Schmidt, B. Mackensen*, W. Schmitz**, H. Greten. Dep. of Medicine, Universi ty Hospital Eppendorf, Hamburg, Dep. Medic ine* and Dep. of Pharmaco logy and Toxicology**, MOnster, Germany

Background: Muscarinic (M) receptors are important for the regulation of gal lbladder contraction. Previous studies have have demonstrated M3 receptors in gallbladder smooth muscle (von Schrenck et al., GE 105:1341-1349, 1993) suggesting that the increase in phosphol ipase 13 activity causes generation of the biologically active isomer 1,4,51P3 and the subsequent increase in force contract ion. However, no studies have demonstrated the effect of cholinergic agonists on the formation of 1,4,51P3. Aim: To characterize the signal trans-duction of the M receptors by studying carbachol-induced changes in 1,4,51P3 formation and contraction. M e t h o d s : Guinea-pig gal lbladder muscle strips were prelabeled with [3H]-inositol for 4 hours and then incubated with 0.1 mM carbachol, [3H] inosi to lphosphate isomers were measured at various t imes (0-90 sec) using HPLC. Contraction was measured in vitro. Resul ts : Carbachol caused a significant, t ime-dependent increase in the formation of various IP isomers, particularly of 1,4,51P3. The time course of the formation of 1,4,5tP3 caused by carbachol paralleled the time course for the carbachol-induced contraction of gallbladder smooth muscle, reaching a significant increase of 1,4,51P3 at 15 sec and a maximal increase (3.5-fold increase of 1,4,51P3, n=l 1) at 60 sac; contraction reached maximal values at 90 sec (4.9- fold increase over basal, n=8). All effects of carbachol were inhibited by atropine (10 p.M). C o n c l u s i o n : In agreement with the previous studies indicating that M3 receptors mediate contraction of gal lbladder smooth muscle, these data provide strong ev idence that carbachol induces contract ion by stimulating the formation of the biological ly active isomer 1,4,51P3.

• SALIVARY SECRETION IS NOT AFFECTED BY ACID IN THE DISTAL ESOPHAGUS BUT ITSELF DECREASES ACID CLEARANCE TIME. J v Sch0nfeld, M Hector, D F Evans, D L Wingate. GI Science Research Unit and Dept of Child Dental Hcalth, London Hospital Medical College, UK

Waterbrash is commonly experienced by patients with gastro-esophageal reflux (GER) and is gcneraUy attributed to an increase in salivary secretion. It is not known, however, whether GER affects salivation. This study was designed to assess the effect of acid in the distal oesophagus on volume and composition of secreted saliva. We also investigated the effect of chewing gum-stimulated whole-saliva secretion on acid clearance. After oesophageal manometry a pH probe was placed 5 cm above the lower esophageal sphincter (LES) in 10 healthy volunteers, aged 21-38 years. An additional paediatric feeding tube was placed 10 cm above the LES to allow infusion of either 20 mls of water or 0. IN hydrochloric acid. Acid clearance time was measured in the upright position with one swallow every 45 s, modifying the quality of the swallows (wet vs. dry), the quality of the material swallowed (saliva vs. water) and saliva secretion (basal vs. stimulated (by a chewing gum base)). Volume, protein concentration and pH of the expectorated saliva were measured. A portable digital recorder was used for acquistion of pH data at a sampling frequency of 0.15 Hz. Results. Gum-stimulated salivary flow was higher than basal flow (mean + SE 26.0 +_. 3.4 vs. 13.2 + 2.0 ml/15 min; p= 0.005). The presence of acid in the lower esophagus did not affect salivary flow; its protein concentration or pH. Acid clearance depended on the quality of swallows and salivary flow.

Acid clearance time (min) Oualitv of swallows Basal salivary flow Stimulated

salivary flow dry 12.6+2.6 9.1+2.3 ns wet (saliva) 6.9+1.9 2.3+0.2 p<0.02 wet (water) 7.8+1.8

We conclude that acid in the lower esophagus does not affect the rate of saliva secretion. The act of chewing gum, however, markedly decreases acid clearance time and this may be useful as a non-pharmacological treatment option in the relief of symptoms caused by gastro-esophageal reflux.

TREATMENT OF MAJOR DEPRESSION DECREASES FUNCTIONAL DISABILITY IN PATIENTS WITH IBD: A PIIX)T STUDY EA Walker, MD Gelfand, AN Gelfand University of Washington and Virginia Mason Medical Center, Seattle WA

Objective: To study the effect of treating comorbid major depression on the perceived functional disabih'ty of patients with inflammatory bowel disease (IBD). Method: Seven IBD patients with confLrmed DSM-III-R major depression completed the Medical Outcomes Study SF-38 (a valid and reliable measure for detecting changes in physical limitations, occupational role, emotional role, social function, pain, mental health, vitality and health perception), and the Hamilton Depression Rating Scale (HAM-D; a quantitative measure of depression severity). Subjects were started on 20rag of paroxetine (a selective serotonin re-uptake inhibiting antidepressant or SSRI), and followed for a total of 8 weeks. After the first month the patients were evaluated to assess treatment effect, and 2 patients had their dosages increased to 40 mg. After the full 8 weeks the patients were re-interviewed, and the SF-36 and HAM-D readministered. Results: Treatment of major depression resulted in the expected decrease in mean HAM- D depression ratings (pre-treatment 27.9 ~.7; post-treatment 7.7 ~.4; t= 12.4, dr=6, p<0.000). In addition, despite any objective indications of decreasing disease severity there was an additional reduction of functional disability on all scales of the SF-36 0dgher scores associated with increased quality of life -- see below).

MOS scale pre-tx postotx l) physical function 82.1 69.2 0.31 role function 3.5 42.8 0.07 emotional role 33,3 57.1 0.14 social function 48.2 66.0 0.10 pain perception 39.8 52.1 0.03 mental health 48.0 75.4 0.02 vitality 23.5 38.5 0.06 health perception 27.8 35.5 0.17

Although some of these differences did not reach statistical significance due to the small number of subjects in the pilot, the absolute differences are both clinically important and would be statistically significant given a proper sample size. Conclusions: This small, uncontrolled pre'hndnary study suggests that treatment of major depression in patients with IBD may be beneficial in increasing quality of life regardless of progression of gastrointestinal disease state.