A350 AGA ABSTRACTS GASTROENTEROLOGY, VOl. 108, NO. 4

O INFLUENCE OF CAPSAICIN-SENSITIVE AFFERENT NEURONS AND NITRIC OXIDE (NO) ON CAERULEIN-INDUCED PANCREATITIS IN RATS. A. Dembinskl Z. Warzecha, P. Ceranowlcz S.J . Konturek. Ins t . P h y s i o l . , Univ. Sch. Med., Krakow, Poland.

Evidence is accumulating that capsaicin-sensltlve afferent fibres play an essential role in the control of pancreatic circulation. Stimulation of afferent neurons by intragastric capsalcln was shown to protect gastric mucosa against damage via NO-dependent mechanism. The aim of present study was to determine the effect of stimulation or ablation by capsaicln of sensory neurons on the course of caerulein-induced pancreatitis (CIP)' We found that pretreatment with capsalcln-stlmulatory dose (0.5 mg/kg ig) alone caused an increase of pancreatic blood flow {PBF) (3OX over control value), and was without any effect on the DNA synthesis, pancreatic weight, RNA, DNA and protein content. Treatment with neurotoxic dose of oapsalcin {I00 mg/kg over 3 dab, s i.e.) caused a reduction by {30X) of PBF followed by a signifioant decrease in RNA content and DNA synthesis (30g). CIP (10 Hgxkg-lx h - l f o r S h) l ed to a significant decrease in DNA synthesis over 80Z, around SOX inhibition of PBF, and significant increase in pancreatic weight, protein content and plasma amylase concentration. Stimulatory doses of capsalcin attenuated the pancreatic tSssue damage in CIP what was manifested by significant reversion in the drop of PBF and DNA synthesis. Capsaicln-lnduced ablation of afferent neurons prior to CIP caused an increase in all indicators of pancreatic damage. Pretreatment with NS-nltro-L-arginine (L-NNA), enhanced caerulein induced pancreatic damage. Deleterious effect of L-NNA was reversed by addition of L-arginine (2xSO mg/kg). Administration of L-NNA together with stimulatory doses of capsaicln during CIP abolished protective effect of capsaicin. Neurotoxic doses of capsaicin were not able to aggravate the damage oaused by L-NNA and caerulein given together. We conclude that stimulation of afferent neurons by capsaicin exerts protective activity against CIP and thls action appears to be dependent on endogenous NO release. Deactivation of affe÷ent neurons by high doses of capsaicin contributes to the severity of pancreatitis. This action involves mainly the ~all in PBF.

OCTREOTIDE IN THE PREVENTION OF AMYLASE INCREASES IN THE SERUM AFTER ENDOSCOPIC PANCREATOGRAPHY Z. D6bronte. L. Juhasz, B. Ker~sz, Z. Tulassay, Markusovszky Tenchi~ Hospital. Szompathely, Tenching Hospital Miskolc, Semmelweis University Medical School, Budapest

There are controversial data about the efficacy of the long-acting somatnstatin analogue, octrcotide in the prevention of pancreatic enzyme changes in the scram following endoscopic retrograde pancreatography. The aim of the trial was to study the effect of octreotide on the rise of pancrentic amylase in the serum following the endoscopic procedure.

Patients and methods: The study was conducted in a prospective random rammer in 9 endoscopic centers. 2102 patients undergoing ERCP were randomly allocated to two groups. In the control group 1028 patients received isotonic sodium--chloride and in the trented group 1074 received 0.1 mg octreotide acetate subcutaneously before and 45 min after the pancrentography. Blood was collected from each patient before and at 6 and 24 hours after ERCP. Both patient groups were well matched with regard to patient ' s characteristics and to endoscopic diagnoses.

Results: Acute pancrentitis developed in 35 patients (in 19 control and in 16 trented patients). After endoscopy the amylase levels in the serum increased at 845 patients in the controls, and at 517 in treated patients. The difference is statistically significant between the groups concerning the enzyme changes (chi-square-test: 7,01, p<0.01). A significant difference could be observed in lllc amylase changes between the two groups at 6 hours after ERCP. The enzyme levels showed only marked elevation in the treated ~onp, however their rises were significant (p <0.05) in the controls.

Conclusion: These finding suggest that the use of long-acting somatostatin analogue ameliorates the amylase increases in the serum a ~ r ERCP.

The participants of the stud)' were: DomjAn L, DObrOnte Z., Farkas I.. Juhasz L.. Lakatos L., Ri~.cz I., Simon L., T~tmok F. The work Ires benn supported by grant OTKA T-013030

• PERITONEAL EXUDATE AS A SOURCE OF ENDOTOXIN IN SEVERE ACUTE PANCREATITIS (SAP). S D0[gn, H Lewis, G Campbell, P Erwin, M McCaigue, MI Halliday, BJ Rowlands. Dept o f Surgery, Queen's University Belfast, N Ireland. INTRODUCTION: Systemic tumour necrosis factor (TNF) has been demonstrated in experimental SAP yet endotoxin, a potent stimulus for TNF activation has not been detected in the vascular compartment. Our aim was to investigate the peritoneal exudate as a potential source o f endotoxin and TNF. The role o f TNF in disease pathogenesis was further studied by evaluating the effect o f Peutoxifylline on survival. METHODS: Study I: SAP was induced in 30 male Wistar rats by the retrograde infusion o f 0.2 ml o f 5% sodium taurocholate at 30 mmHg into the pancreatic duct. Saline infusion was used in 24 control (COIN) rats. Animals were allocated to 3 groups and had sampling o f peritoneal exudate and venous blood at 2, 3 and 12 hr. CON rats had lavage o f the peritoneal cavity with a volume of saline equal to the exudate in SAP rats at that time point. Samples were assayed for endotoxin (Chromogeaic LAL) and TNF (ELISA). Study 2: The cfft~-t of intraperitoneal (ip) PTF on survival of SAP rats was assessed, Group A (n=10) were administered PTF 12mg/100g ip, Group B (n=10) the same volume o f saline ip. RESULTS: expressed as median (inter-quartile range) Per = Peritoneal exudate Ven = Venous Endo = endotoxin ND •not detected. * = 3< 0.05 for SAP v CON at same time Mann-Whitne

pg/mJ SAP 2 CON 2 SAP 3" CON 3 SAP 12 CON 12 End0 Per 17 (I 14)* ND 127 (120)* biD 24 (45)* ND

TNF Ven 66 (30)* 27 (16) 35 (26) 25 (28) 72 (53)* 18 (25) TNF Per 79 (42)* 33 (22) 19 (25) 11 (25) 80 (47)" 23 (24) All venous samples were negative for endotoxin. Survival in Group A at 48 hr was 100°,4 and in Group B 40%. CONCLUSIONS: The exmdate seen in this model o f SAP is a significant source o f endotoxin and TNF. Pentoaffylline administered intraperitoneally has a beneficial effect on survival suggesting a role for TNF in disease pathogenesis and therapeutic potential.

LONG-TERM RESULTS OF ENDOSCOPIC PANCREATIC DRAINAGE IN CALCIFIED CHRONIC PANCREATITIS (CPP); FACTORS ASSOCIATED WITH A FAVOURABLE OUTCOME. Dvm0nceau , J. Devih-e, O. Le Moine, M. Delhaye, A. Vandermceren, M Baize, J. Love, M. Cremer, Dept. of Crastroenterology and Hepato-pancreatology, Erasme University Hospital,Brussels,Belgium.

INTRODUCTION, The aim of therapeutic endoscopy in CPP, as that of surgery, is to reduce increased in~aducta] pressure by endoscopic pancreatic spkincterotomy and stone clearance. METHODS. Feurb,--six patients with endoscopica]ly treated CCP were retrotpcctively assessed with a minimal follow-up of 2 years. None of them required pancreatic stem treatment placement or surge D ' as initial treatment Pain recurrence, weight and diabetes were noted. RESULTS.

Pmlnet* pattmts (~.I). Poin recurrence. (Fig. 2)

o v~ (A) ~ (e)

~' [ m Totol ~ Predicled I

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No severe complication or mortality related to treatment were noted. The recurrence of'pain during the first 2 yen~ of foUow-up is shown i . Fig l .Tbe factors associated whb pain ~ during this period were (1) the presence of main pancreatic duct lesions (substenosis or stop) (2) a long disease-duration and (3) a high frequency of pain attacks before treatment. They allowed to construct a function which discriminated patients with and wiftmut pain recurrence (Fig. 2). The body weight increased from 62+12 to 64.5+14 kg (13<0.05). Diabetes appeared in 3 cases. CONCLUSIONS, In selected patients with CCP, long-term results of endoscopic management are similar to those of surgery with the major advantage that the treatment can be safely repented ffnecessary. The data support the concept OF enrly treatment for better results in CCP.