A710 AGA ABSTRACTS GASTROENTEROLOGY, Vol. 108, No. 4

DIFFERENT INCIDENCE AND ORGANIZATION OF CLUSTERED CONTRACTIONS IN THE HUMAN DUODENUM AND JEJUNUM. At. Wilmer. T. Andreoli, G. Coremans, J. Jansseus. Center for G.I. Research, University of Leuven, Leuvea, Belgium.

Clustered contmctious (CCs) is a pattern of motor activity observed in the human small intestine both in health and disease. CCs are effective in propulsion over short distances, The aim of this study was to compare in healthy subjects the incidence and characteristics of CCs in the duodenum versus the proximal jejunum. Methods: 15 healthy volunteers (age 20-25 yrs, 9 m) were studied by ambulatory 24-hour manometry (Synect ics Digitrapper) using 2 groups of 3 sensors each 4 cm apart, in the duodenum and in the proximal jejunum. The distance between the two groups of sensors was 30 cm. Two identical 800 kcni meals were admiustered during the study. Visual analysis was used to identify CCs in either duodenum or jejunum during both phase 2 and the fed period according to the following criteria: a group of at least 2 regular contractions per channel with an inteveontractile interval of I to 6 see, propagating over at least 8 eva, preceded and followed by at least 30 see of motor quiescence. Computer analysis was used to describe parameters characterizing these CCs. (Statistics: means±SD, paired t-test, significance if p<0.05). Results: A total of 472 CC.s were identified, 340 in the duodenum and 132 in the jejunum. The characteristics of these CCs were as follows:

# CCs/hr #cont/ CC dur of cont amn of cont vrov vei CC

duod jej duod jej duod jej duod jej duod jej

ph2 1.0~ 0.4+ 3.3+ 4.1± 4.3± 4.2+ 36± 35± 1,4± 2.1± 0.7 0.4 * 0.7 !.9 0.6 0.7 7 7 1.1 1.4

fed 1.8± 1.0~: 3.1± 4.3± 4.1± 3.3± 33± 25± 1.6± 1.8± 1 1.1" 0.6 1 . 0 . 0.7 0.5* 4 5* 1 1.5

(tout = contractions, dur = duration in see, amp = amplitude in mmHg, prop vel = propagation velocity of CC in cm/sec, * = p < 0.01). Conclusions: in healthy man, clustered contractions occur significantly more frequently in the duodenum than in the jejunum, both in the interdigestive and digestive state. While in the interdigastive state the characteristics of CCs are similar in the duodenum and jejanum, in the digestive statejejanal CCs are chamcterised by a higher number of individual contractions per cluster, a shorter duration and a lower amplitude of individual cont rac t ions . Presumably, these differences reflect a physiologic adaptation of different segments of the small bowel to regulate the rate of transit of incoming chyme.

• NITRIC OXIDE MEDIATES THE RAPID GASTROINTESTINAL TRANSIT OF ENDOTOXEMIA. D.J. Wirthlin, S.T. Spates, J.J. Cullen, J.L.

Conklin ct, L Murray ct, D.K. Caropreso, K.S. Ephgrave. Departments. of Surgery

and Internal Medicine c~, University of Iowa College of Medicine, Iowa City, IA. Endotoxin results in elimination of the interdigestive migrating myoelectric complex and is diarrhcogenic in rats (J. Gastrointestinal Mot 5:212) We hypothesized that the disrupted transit that occurs during endotoxemia is mediated by nitric oxide (NO), and that the inhibition of NO synthesis will normalize gastrointestinal transit. METHODS: Following placement of an intravenous (IV) line and recovery, rats were given E. Coli !ipopolysaccharide (LPS) bolus, 10 mg/kg/IV, LPS bolus 10 rag&g/IV + dexamethasone 3 mg/kgaV, or 0.9% NaCI (controls). To determine activity of NO synthase in the small intestine, the conversion of L-3Harginine to L-3Hcitrulline was measured. To determine gastrointestinal transit, garage feeding of a nonabsorbable marker was given (0.1 ml Evans blue) and rats were divided into five groups: 0.9% NaCI 1 ml/hr/IV x 5 hr (control); LPS bolus 10 mg/kg/1V; LPS + NG-mone-methyl-L- arginine (L-NMMA) 10 mg/kg/hr x 5 hr; LPS + L-arginine 12.5 mg/kg/hr x5 hr; or LPS + L-NMMA + L-arginine. RESULTS: Compared to control, LPS increased the constitutive and inducible forms of NO synthnse (picomoles/mg/min) in the small intestine and these effects were not blocked by dexmnethasone (constitutive: control, 0.1+0,1 vs LPS, 0.5+0.1' vs dexamethasone, 0.4+0.1', inducible: control, 0.03+0.01 vs LPS, 0.29+0.07* vs dexamethasone, 0.13+0.04", means+SEM, *p<0.05 vs control). Endotoxemia accelerated gastrointestinal transit compared to controls (Table). This rapid gastrointestinal transit induced by both LPS and LPS + L-arginine was reversed by L-NMMA. CONCLUSIONS: NO plays a major role in mediating the rapid gastrointestinal transit during endotoxemia. Support: Veteran's Affairs Merit Review grant.

LPS+ LPS+ LPS+ L-arginine

Control LPS L-NMMA L-arginine +L-NMMA 59+2 90+5 * 57+5 # 94+8 * Gastrointestinal

transit (cm from pylorus)

Means+SEM, *p<0,05 vs control, # p<0.05 vs LPS.

EFFECT OF ERYTHROMYCIN ON PANCREATIC POLYPEPTIDE IN PA- TIENTS WITH CIRRHOSIS OF THE LIVER. B.LM. Witteman, W.P.M. Hopman, P. Netten I, Th. Thien ~, J.B.M.J. Jansen. Dept.s. of Gastroenterology & Hepatology and Internal Medicine t, University Hospital Nijmegen, The Netherlands.

The release of pancreatic polypeptide (PP) in response to intravenous erythromycin (ERY) is dependent on intact vagal cholinergic pathways and an intact antrum. Since autonomic neuropathy (AN) of the gastrointestinal tract damages vagal nerve integrity and complicates the course of chronic liver disease, we have studied whether the PP response to intravenous ERY and to modified sham feeding (MSF) is diminished in patients with cirrhosis of the liver. We also performed cardio-Vascular reflex tests (FINAPRES). Results are given as median and range. Eleven patients with liver cirrhosis (LC; 4F,7M; 46 [26.-65]yrs, Child B: 3; Child A: 8), 21 healthy controls (HS; 10E, l lM; 46 [22-72]yrs) and 5 vagotomized patients (VP; IF,4M; 53128-68]yrs) were studied. Results. I.V. infusion of ERY dose dependently stimulated PP in HS: 948[326-2964] pM*20min (0.4 mg/kg.15min) and 11611514-7608] pM*20min (1.2 mg/kg.15min). In LC (5091121-2290] and 776129-2670] pM*20min, respectively), and VP (275[-121-571] and 443184-1680] pM*20min, respecti- vely) these responses were significantly (t)<0.05) lower. In 5 LC patients PP response to ERY (1.2 mg/kg.15min) was below the lowest value in HS. FINAPRES was abnormal in 4 LC-patients (36%), butin none of the HS. MSF in LC-patients (923[65-4505] pM*60min) was not significantly different f r o m HS (19301473-5115] pM*60min). There was no significant correlation between FINAPRES and ERY results. C0nelusion: PP responses to ERY but not to MSF is decreased in LC-patients, where AN is freciuently found. Because damage to different autonomic nerve systems may occur independently of one another, we speculate that the PP response to ERY may contribute tO the assessment o f autonomic nerve function of the gastrointestinal tract in LC-patients.

PANCREATIC POLYPEPTIDE RESPONSE TO ERYTHROMYCIN IN PATIENTS WITH INSULIN' DEPENDENT DIABETES MELLITUS AND CARDIOVASCULAR AUTONOMIC NEUROPATHY. B.J.M. Witteman, K. Edwards-Teunissan, W.P.M. Hopman, J Lutterman ~, P.M. Netten ~, Th. Thien ~, J.B.M.J. Jansen. Depts. of Gastroenterology & Hepatology and Internal Medicine ~, University Hospital Nijmegen, The Netherlands.

Pancreatic polypeptide (PP) release in response to intravenous erythromycin (ERY) is dependent on intact vagal cholinergic pathways and requires an intact antrum. Since autonomic nenropathy of the gastrointestinal tract damages vagal nerve integrity and frequently complicates the course of diabetes mellitus, we have studied the PP response to erythromyein. Methods: The PP response was studied in 17 insulin dependent diabetics (9F; 8M; 60[30- 79] yrs) with abnormal cardiovascular reflex tests and with (DMI: n=8) or without (DM2: n=9) symptoms suspicious of autonomic neuropathy of the gastrointestinal tract, like pyrosis, nausea, vomiting, anorexia, ructus, fullness, bloating and retrosternal or upper abdominal pain. Twenty-one healthy controls (I-IS: 10F; I lM; 46122-721 yrs) and 5 vagotomized patients (TV: IF; 4M; 53[28-68] yrs) were also included in the study. Results: IV infusion of ERY stimulated PP in HS: 9481326-29641 pM*20min (0.4 mg/kg.15min) and 11611514-7608] pM*20min (l.2mg/kg.15min) and DM2 (14541321-2996] and 22331130-4365] pM*20min, respectively). The integrated PP responses to ERY were significantly (13<0.01) lower in DM1 (452[-81-1513] and 6081123-13101 pM*20min, respectively), and TV (275[-121-571] and (443184~1680] pM*20min, respectively), when compared with HS and DM2. Conclusion: In a subgroup of DM patients with gastro-intestinal complaints suspicious of AN, ERY stimulated PP is decreased.