A376 AGA ABSTRACTS GASTROENTEROLOGY, Vol. 108, No. 4

CHANGES OF SERUMAMYLASE AND SYMPTOMS IN ERCP INDUCED ACUTE PANCREATITIS. A.Mirmiran-Yazdy, S. Bank, CQ Pan, B. Stark, Division of Gastroenterology, Long Island Jewish Medical Center, New Hyde Park, NY, the Long Island Campus for Albert Einstein College of Medicine.

Backqround: Endoscopic Retrograde Cholangiopan- creatography (ERCP) induced acute pancreatitis has been reported with an incidence of 1% to 17% of patients having the procedure. Publishedstudies have shown that hyperamylasemia occurs as early as two hours after ERCP. The duration, peak time and level of amylase that are associated with symptoms are uncertain. Methods: Our study reviewed the recordsof 20 patients who had ERCP induced acute pancreatitis. The data include serum amylase levels at 6, 12~ 24 hours and at the following 24 hour intervals until the levels returned to normal; symptoms of fever~ new onset or new pattern of abdominal pain, nausea, vomiting, and white cell count after ERCP. Results: All patients had hyperamylasemia (>300 u/L) 6 hours after ERCP. In 80% of patients amylase levels peaked at 12 hours and 20% at 6 hours. Hyperamylasem~a(>300 u/L) remained elevatedat 48 hours then returned to normal at 72 to 96 hours. The clinical presentation varied in different cases except the abdominal pain. Our study showed that during the first 6 hours all patients (i00%) had abdominal pain, 80% developed fever, 50% had an elevated white blood cell count, and 35% developed nausea and vomiting. Most symptoms were con- current with hyperamylasemia. In 60%of patients symptoms persisted after serum amylase returned to normal. Conclusion: In our study~ the symptoms of ERCP-induced acute pancreatitis associated with hyperamylasemia (>300 u/L) developed within 6 hours after the procedure. Implication: Patients having ERCP should be monitored for at least6 hours after the procedure. New onset or new pattern of abdominal pain and hyperamylasemia (>300 u/L) strongly suggest ERCP ~ induced acute pancreatitis. Asymptomaticpatients with normal amylase are unlikely to develop pancreatitis after 6 hours.

• DOSE DEPENDENCE OF ECTOPIC PROTEASE ACTIVATION AND PANCREATIC INJURY IN HYPERCALCEMIA-INDUCED EXPERIMENTAL PANCREATITIS. K. Mithffer, T.W. Frick, C. Femandez-del Castillo, K.B. Lewandrowski, D.W. Rattner. A.L. Warshaw. Departments of Surgery and Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA.

Clinical reports have shown the association of high calcium doses with the development of pancreatic injury after cardiopulmoaary bypass. Recent experimental studies demonstrated development of acute pancreatitis with increased intrap~creatic trypsmogen activation after administration of high quantities of calcium. In order to investigate if this effect of calcium is limited to high doses, rats randomly received bolus injections of 2ml 0.9% NaCI. or CaCI 2 at 50mg/kg, 100mg/kg, 150mg/kg or 200mg/kg (n=5 each). Changes of serum [Ca2+], serum amylase activity, pancreatic Trypsinogen Activation Peptide (TAP), and pancreatic wet/dry weight ratio were then evaluated at lh following CaCI2 administration. RESULTS: All investigated parameters remained unchanged after saline infusion. Serum [Ca 2+] increased in proportion to the amount of infused CaCI2

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(P< 0.001, r=0.96). Similarly, serum amylase activity and pancreatic wet/dry weight ratio both increased in a dose dependent manner (Figures). While tissue TAP was not significantly elevated after 50 mg/kg CaCI 2 (1044-22 nM/L. g), a significant rise of TAP to 236 4- 37, 247 4- 60, and 293_+ 72 nM/L • g (P < 0.05) was observed lh after infusion of 100. 150. and 200 mg/kg, respectively. CONCLUSIONS: These results indicate a direct relationship between the degree of hypercalcemia and severity of biochemical and morphologic damage in the pancreas after acute hypercalcemic challenges.

• SUBCELLULAR REDISTRIBUTION OF LYSOSOMAL ENZYMES IN EXPERIMENTAL ACUTE PANCREATITIS IS ASSOCIATED WITH INCREASED PROTEASE ACTIVATION IN THE INTRAACINAR ZYMOGEN COMPARTMENT. K. Mithffer, C. Femandez-del Casfillo, D.W. Rattnerl A.L. Warshaw. Department of Surgery, Massachusetts General Hospital, Boston, MA.

Ectopic activation of pancreatic zymogens is believed to be a key event in the pathogenesis of acute pancreatitis. Intracellular redistribution of lysosomal enzymes into the zymogen compartment has been suggested as a potential mechanism for activation of inactive protease precursors and possible initiating event in acute pancreatitis. To investigate the pathophysiologic relevance of lysosomal enzyme redistribution f o r premature protease activation, rats were randomly infused with 0.9% NaC1 or caerulein at 0.25#g/kg/h or 5#g/kg/h for periods from 15min to 3 hrs (n > 4 at each time point). Early changes of serum amylase activity, pancreatic wet/dry weight ratio, concentration of trypsinogen activation peptide (TAP) in pancreatic tissue homogenates, and distribution of cathepsin B activity and TAP in the subcellular compartments after subcellular fractionation were investigated, RESULTS: No significant changes were noted in animals infused with saline or 0.25#g/kg/h caerulein. 5#g/kg/h caerulein increased pancreatic TAP content within 15 min (P < 0.05) while significant hyperamylasemia and pancreatic edema developed within 30 rain. All parameters increased continuously for 3 hrs. Activity of Cathepsi n B in the zymogen compartment increased continuously over the 3h period (P<0.01). Concomitantly, increasing TAP generation was noted in the zymogen compartment (P<0.05) which correlated with the observed changes of Cathepsin B activity in the same compartment (r=0.87, P<0.001). CONCLUSIONS: Trypsinogen activation represents an early event in caerulein-induced acute pancreatitis. Redistribution of lysosomal enzymes into the subcellular zymogen compartment is associated with increased intracompartmental trypsinogen activation. This finding supports the relevance of the redistribution phenomenon in the early intraacinar changes in acute experimental pancreatitis.

• NEUROHORMONAL REGULATION OF PANCREATIC EXOCRINE FUNCTION IN A NEW RAT MODEL WITHOUT GENE EXPRESSION OF CHOLECYSTOKININ-A RECEPTOR. K.

' M. Masuda , 1'. K a w a n a m i , A. Funakosh'iT. t o f Clinical Phys io logy, Tokyo Metropol i tan

nstitute of Gerontology, Tokyo-173, National Kyushu Cancer Center , Fukuoka-815

We have reported that Otsuka Long-Evans Tokush ima Fatty (OLETF) rats revealed none or less express ion of cholecystokinin (CCK)-A receptor gene in the pancreas, and that the pancreas of this strain of rats did not respond CCK stimulation (BBRC, 1994). In the present study, we examined whether the pancrea t i c responses to hormonal and neural st imulations except for CCK in OLETF rats were maintained. M e t h o d s : The rats were prepared with cannula draining bile and pancreatic juice, separately and with a duodenal cannula and a jugular v e i n cannula. In Some animals , an additional cannula was inserted into the left lateral ventricle. The pancrea t i c r e sponse s t o i n t r a v e n o u s in jec t ion o f neuromedin C, secretin and acetylcholine, to intraduodenal injection of capsaicin (013 mg/rat) which st imulated vagal afferent nerve, to cerebroventricular injection of TRH which s t imulates vagal efferent nerve and to intragastric injection of liquid meal, were examined in vivo without anesthesia, and compared with t h e control (Long-Evans -Tokush ima = LETO) rats. Moreover, the gene expres.stons of CCK receptors in the small intest ine were examined by RT-PCR method, because the distribution of CCK receptor binding sites has been reported in the vagal afferent nerve terminal. R e s u l t s : Pancreatic responses to graded d o s e s of intravenous injection of secretin arid acetylcholine, and to intracerebroventricular a d m i n i s t r a t i o n ' o f TRH were comparable for OLETF and LETO rats. Howeve r , responses to intravenous injection of neuromedin C to intraduodenal injection of capsaicin and to intragastr ic ' injection of liquid meal were impaired in OLETF rats. T h e CCK-A recelJtor mRNA was not expressed in the small intestine of OLETF rats but was in LETO rats. C o n c l u s i o n s : The pancrea t i c r e s p o n s e s to va r ious s t imulat ions i n OLETF rats were well conserved except for the case of involvement of CCK-A receptor functions.