Does stress play a role in the development of severe pancreatitis in rats?

The purpose of this study was to investigate whether stress plays a role, morphologically and enzymatically, in the development of severe pancreatitis in rats. Acute hemorrhagic pancreatitis was induced by two intraperitoneal injections of cerulein (40 micrograms/kg body wt) at intervals of 1 h under water-immersion stress for 5 h, whereas water-immersion stress alone did not induce any morphologic and enzymatic changes in the pancreas. In this model, hemorrhagic pancreatitis developed continuously, and the serum amylase level and activation of zymogen proteases in pancreatic tissue were significantly higher than in cerulein-induced pancreatic tissue 5 h after the first cerulein injection. Furthermore, the effects of cerulein on the serum amylase level and activation of zymogen proteases were dose related. Even 5 micrograms/kg body wt of cerulein, which did not induce any evident edematous change in the pancreas, could activate the zymogen proteases of pancreatic tissue fairly well under water-immersion stress compared with pancreatitis induced by 40 micrograms/kg body wt of cerulein alone. These results indicate that stress accelerates the activation of zymogen proteases induced by cerulein and suggest the possibility that stress may play some role in the development of severe pancreatitis.     

Influence of changes in pancreatic tissue morphology and capillary blood flow on antibiotic tissue concentrations in the pancreas during the progression of acute pancreatitis.

BACKGROUND: The ability of an antibiotic to reach bactericidal concentrations in tissue depends on numerous factors including tissue composition and regional perfusion. Although necrotising pancreatitis is characterised by progression of pancreatic necrosis over at least 96 hours and microcirculatory alterations, the impact of these changes on the concentration of antibiotics in the pancreas has not yet been investigated. AIM: To determine and compare pancreatic tissue concentrations of imipenem and cefotaxime at different stages of acute necrotising pancreatitis in an animal model that has been shown to mimic closely the pathomorphological and bacteriological features of severe human pancreatitis. METHOD: Acute necrotising pancreatitis was induced in rats by a standardised intraductal infusion of glycodeoxycholic acid and intravenous cerulein. Six hours (n = 16) and 48 hours (n = 16) after induction of pancreatitis, the animals were randomised for intravenous therapy with either imipenem or cefotaxime. Fifteen minutes after injection of the antibiotic, the animals were killed. Blood and the head of the pancreas were collected for determining imipenem or cefotaxime in serum and tissue; the splenic portion of the pancreas was prepared for histological examination. In an additional set of identically treated animals, pancreatic capillary blood flow (PCBF) was assessed by intravital microscopy before induction of acute necrotising pancreatitis and at the time of antibiotic therapy. RESULTS: Imipenem accumulates in the pancreas in the initial phase of acute necrotising pancreatitis characterised by pronounced oedema and decreased PCBF, and tends to decrease with resolution of the oedema and the progression of acinar cell necrosis in the later course of the disease. Concentrations of cefotaxime are low in oedematous pancreatic tissue early after induction of acute necrotising pancreatitis and increase with the resolution of oedema and normalisation of PCBF. CONCLUSIONS: Concentrations of antibiotics in the pancreas vary in acute necrotising pancreatitis, depending on changes in pancreatic tissue morphology and capillary blood flow. This suggests that antibiotic tissue concentrations may not be consistent from one agent to another and that efficacy of antibiotics in acute pancreatitis cannot be estimated solely on the basis of their pharmacological and microbiological properties.     

Effects of somatostatin on acute canine experimental pancreatitis

Somatostatin is an inhibitory hormone that decreases the secretion and end organ response of cholecystokinin (CCK). Inhibition of hormonal stimulation of pancreatic exocrine secretion by somatostatin may improve the course of acute pancreatitis. Anesthetized dogs underwent cholecystectomy and cannulation of the pancreatic duct, thoracic duct, and portal vein. Twenty experiments were performed in random order with 5 dogs in each group. Hourly measurements of lymph flow and portal and thoracic duct amylase were made. Portal blood insulin, glucagon, and CCK concentrations were determined by radioimmunoassay on samples obtained at the beginning and end of the experiments. Pancreatitis was induced by injecting, under constant pressure, 10 ml bile into the pancreatic duct during 1 min. Somatostatin was administered intravenously (20 micrograms/kg/hr). After 5 h, the dogs were killed, pancreas glands removed and weighed and tissue samples obtained for histologic evaluation. There was a significant increase in lymph amylase output and portal venous amylase and CCK concentrations in the dogs with pancreatitis compared to the control dogs. In dogs with pancreatitis, lymphatic amylase secretion and portal CCK concentrations were significantly decreased by somatostatin. Somatostatin did not significantly alter portal amylase concentrations, pancreas gland weights or histologic inflammation when compared to values from dogs with pancreatitis not treated with somatostatin.     

Penetration of meropenem and cefepim into pancreatic tissue during the course of experimental acute pancreatitis

INTRODUCTION: Recent data from experimental and clinical studies suggest that the antibiotics showing good penetration into the pancreas may reduce mortality by preventing pancreatic infection, which is the most important prognostic factor in acute pancreatitis. AIM: To determine and compare pancreatic tissue concentrations of meropenem and cefepime at different stages of acute necrotizing pancreatitis in an animal model that has been shown to closely mimic severe human pancreatitis. METHODOLOGY: Acute necrotizing pancreatitis was induced in rats by a standardized intraductal infusion of glycodeoxycholic acid and intravenous cerulein. Six hours (n = 30) and 48 hours (n = 30) after induction of pancreatitis, the rats were randomized to receive an intravenous 20 mg/kg injection of either meropenem or cefepime. Blood and the head of the pancreas were collected for determining antibiotic concentrations by high-performance liquid chromatography. RESULTS: Meropenem concentrations in the pancreas at 6 hours of acute pancreatitis increased significantly and decreased at 48 hours of the disease, but were still higher than that in controls. Concentrations of cefepime in necrotic pancreatic tissue were significantly low either during the initial or later phase, but lower in latter, in which the necrosis was more evident. Tissue/serum concentration ratios of meropenem were significantly higher than those of cefepime. However, tissue concentrations of both antibiotics are much higher than the minimum inhibitory concentration values for the common microorganisms involved in pancreatic infections. CONCLUSION: Although both antibiotics penetrate into the necrotic tissue in sufficient therapeutic concentrations, penetration of meropenem is much better than cefepime. However, good tissue penetration may not solely indicate efficacy of that antibiotic. Therefore, further experimental and clinical studies are needed to determine the therapeutic and prognostic efficacy of these agents.     

Azlocillin und Mezlocillin: Zwei neue semisynthetische Acylureidopenicilline

The pharmacokinetic parameters of two new ureido-penicillins (azlocillin and mezlocillin) were determined in 12 healthy subjects after a half-hour continuous infusion of 5,000 mg. The agar diffusion test (test strain Bacillus subtilis ATCC 6633) was used for the microbiological assays. The mean azlocillin serum concentration after the half-hour infusion was 431.0 +/- 75.0 microgram/ml; after eight hours it had fallen to a mean value of 4.7 +/- 2.6 microngram/ml. The mean elimination half-life was 77.5 +/- 10.4 minutes, and the relative distribution volume was 19.4 +/- 1.9% of the bodyweight. At the end of the infusion, mezlocillin showed a mean serum concentration of 426.0 +/- 61.0 microgram/ml and after eight hours an average of 1.1 +/-0.9 microgram/ml; the half-life was shorter (56.9 +/- 9.9 minutes) and the distribution volume lower (14.8 +/- 3.1%) than that of azlocillin. The renal clearance values measured in three subjects during a four-hour continuous infusion were: azlocillin 111.6 ml/min/1.73 m2, mezlocillin 121.5 ml/min/1.73 m2. The kinetic behaviour of the two ureido-penicillins was essentially very similar to that of ampicillin and carbenicillin, 38 patients with bronchopneumonia, cholangitis or urinary tract infections, which in some instances were severe, were treated for an average of 10 days with an average daily dosage of 3X4.0 g azlocillin or 3X5.0 g mezlocillin. 30 patients showed clinical improvement, and in 17 of these the pathogen was eliminated. These therapeutic results appear more favourable than those obtained with the newer aminoglycoside antibiotics (amikacin, sisomicin); in particular the drug was well tolerated.     

Human pancreatic tissue concentration of bactericidal antibiotics.

Pancreatic infection represents the most important cause of fatal outcome in human acute pancreatitis. In a comparative analysis, human pancreatic tissue concentrations of 10 different bactericidal antibiotics were determined in 89 patients undergoing pancreatic surgery. Concentrations of the antibiotics were determined in the blood and pancreatic tissue using high-pressure liquid chromatography. Pancreatic tissue concentrations 120 minutes after intravenous administration were as follows: mezlocillin, 19.0 mg/kg; piperacillin, 20.3 mg/kg; cefotaxime, 9.1 mg/kg; ceftizoxime, 7.9 mg/kg; netilmicin, 0.4 mg/kg; tobramycin, 0.4 mg/kg; ofloxacin, 1.7 mg/kg; ciprofloxacin, 0.9 mg/kg; imipenem, 6.0 mg/kg; metronidazole, 3.5 mg/kg. Three groups of antibiotics were established: group A, substances with low tissue concentrations (netilmicin, tobramycin), which were below the minimal inhibitory concentrations of most bacteria found in pancreatic infection; group B, antibiotics with pancreatic tissue concentrations which were sufficient to inhibit some but not all bacteria in pancreatic infection (mezlocillin, piperacillin, ceftizoxime, cefotaxime); group C, substances with high pancreatic tissue levels as well as high bactericidal activity against most of the germs present in pancreatic infection (ciprofloxacin, ofloxacin, imipenem). These data could serve as the basis for adequate antibiotic prophylaxis or treatment of pancreatic infection.     

Manifestations of experimental acute pancreatitis in young and old rats

Two kinds of experimental pancreatitis were induced in young (4-6 month) and old (25-27 month) female Wistar rats: acute edematous pancreatitis was induced by intraperitoneal administration of a high dose of cerulein (40 micro/kg x 2) and acute hemorrhagic pancreatitis was intraductal injection of 1% deoxycholic acid. After these treatments, the plasma amylase concentration and pancreatic wet weight were determined and the pancreas was examined histologically. In the groups with cerulein induced pancreatitis one of eight old rats died, whereas all five young rats survived. There was no specific finding macroscopically in the liver, kidney, lung or heart of old rats at autopsy after cerulein injection. The plasma amylase concentration and the pancreatic wet weight were significantly increased by administration of cerulein or deoxycholic acid in both young and old rats. There was no significant difference in the plasma amylase concentrations in young and old rats after the induction of acute pancreatitis. The increase in pancreatic wet weight was less in old rats than in young ones after deoxycholic acid treatment, but similar in the two groups after cerulein injection. The extents of histological changes were also similar in young and old rats. Thus, no evidence that aging increases susceptibility to pancreatitis was obtained.     

Comparison of 11C-L-methionine uptake by the parotid gland and pancreas in chronic pancreatitis studied by positron emission tomography.

L-methionine uptake by the parotid gland and pancreas has been compared in 27 patients using a non-invasive methodology. L-methionine was labelled with 11C, a positron emitter with a short half life produced in a cyclotron. 11C-L-methionine concentration was measured in the parotid glands and in the pancreas by external detection using a positron emission tomographic system. 11C-L-methionine uptake by the parotid glands was 4.3 X 10(-3) +/- 1.9 X 10(-3)% of the injected dose per millilitre of tissue (mean +/- SD) in a group of 11 normal non-alcoholic subjects. The uptake was 3.6 +/- 1.3 (X10(-3) in a group of nine alcoholic subjects without pancreatic disorder and it was 4.9 +/- 1.5 (X10(-3) in a third group of seven patients with chronic pancreatitis. These values did not significantly differ. In contrast median pancreatic uptake of 11C-L-methionine was nil in chronic pancreatitis and was lower than that seen in normal subjects (15.3 X 10(-3)% ml, p less than 0.001) and in alcoholic subjects (11.5 X 10(-3)% ml, p less than 0.002). Thus neutral long chain amino acid transport in the parotid gland appears to be independent of that in the exocrine pancreas in chronic pancreatitis. This absence of relationship between the parotid gland and the pancreas in pancreatic disease is in contradiction with the demonstration made in animals of an interaction between these two glands. These results, however, are in agreement with the conclusions drawn from the data collected from the saliva test used by several authors.     

Plasma lactoferrin levels in patients with chronic calcifying pancreatitis

Lactoferrin is a nonenzymatic secretory protein of human pancreas specifically increased in the external pancreatic secretion of patients with chronic calcifying pancreatitis. The possibility of an elevated concentration of plasma lactoferrin level in these patients needed to be explored even if the low pancreatic concentration of the protein did not favor this hypothesis. As expected, no increase could be observed between the plasma lactoferrin level of 16 patients with chronic calcifying pancreatitis (131 +/- 15 micrograms/l), compared to 17 controls (166 +/- 11 micrograms/l) and 15 patients with different organic diseases (187 +/- 18 micrograms/l).     

Evaluation of a range of antimicrobial agents against the parasitic protozoa, Plasmodium falciparum, Babesia rodhaini and Theileria parva in vitro

Eighteen antimicrobials commonly used in tissue culture were screened in three different protozoan test systems in order to establish their suitability for routine inclusion in protozoal cultivation systems. The human malaria parasite, Plasmodium falciparum, was inhibited by more than half the antibiotics tested at concentrations recommended for normal tissue culture use. Eight compounds were well tolerated and thus could be used prophylactically to prevent microbial contamination. These antimicrobials were the bactericidal aminoglycoside antibiotics, streptomycin, gentamicin and kanamycin, the bacteriostatic protein synthesis inhibitors, chloramphenicol and chlortetracycline and the antifungals, 5-fluorocytosine, nystatin and amphotericin B. Babesia rodhaini and Theileria parva were less sensitive than P. falciparum and tolerated all 18 compounds at concentrations well above 100 micrograms ml-1. Extension of the study to examine direct antiprotozoal action of these and other antimicrobials not normally used in culture confirmed that P. falciparum was significantly more sensitive than the other parasites. Tylosin, rifamycin, gramicidin D and valinomycin were all strongly antimalarial with IC50 values of 0.245, 1.20, 1.3 X 10(-3) and 1.9 X 10(-3) micrograms ml-1 respectively. This compares with a value of 1.35 X 10(-2) micrograms ml-1 for the standard antimalarial, chloroquine. Only valinomycin and, more particularly, gramicidin D were significantly active against B. rodhaini and T. parva. Gramicidin D was more effective, but more toxic, than the standard antiprotozoal agents tested at curing in vivo malarial and babesial infections in mice.     

Role of endogenous platelet-activating factor in caerulein-induced acute pancreatitis in rats: Protective effects of a PAF-antagonist

The role of endogenous platelet-activating factor (PAF) in the pathogenesis of acute pancreatitis was investigated by determining whether CV-6209, a selective PAF antagonist, confers protection against caerulein-induced acute pancreatitis in rats. Continuous intravenous infusion of caerulein (5 micrograms/kg x h) induced time-dependent increase in serum pancreatic enzymes, pancreatic weight, and protein content of the pancreas, and produced histologic evidence of acute pancreatitis. Pretreatment with CV-6209 (1 mg/kg) significantly inhibited the elevation of serum pancreatic enzymes, pancreatic weight, and protein content of the pancreas. Caerulein-induced tissue oedema and recruitment of leucocytic cells were markedly ameliorated with CV-6209. Platelet-activating factor may be released endogenously and may play a role during acute pancreatitis.     

Mechanism of increased exocrine pancreatic secretion in pancreatic juice-diverted rats

We investigated a possible role of endogenous cholecystokinin-pancreozymin (CCK-PZ) in the mechanism of exocrine pancreatic secretion after excluding pancreatic juice from the intestine in rats. Fasting plasma immunoreactive CCK-PZ was determined in normal rats, in rats with pancreatic duct ligation, and in sham-operated rats. The mean fasting plasma CCK-PZ concentration of rats with pancreatic duct ligation, 25.1 +/- 2.0 pM, was significantly greater (p less than 0.001) than those of normal and sham-operated rats, 14.3 +/- 1.7 and 11.5 +/- 2.2 pM, respectively. Whereas mean postprandial plasma CCK-PZ concentrations of normal and sham-operated rats were significantly greater (p less than 0.001) than their fasting levels, no significant increase occurred in the rats with pancreatic duct ligation after a meal. The mean fasting plasma CCK-PZ concentration of rats with pancreatic duct ligation was comparable to the mean postprandial CCK-PZ level of normal and sham-operated rats. To determine a possible role of circulating endogenous CCK-PZ on the pancreatic secretion, anesthetized rats were prepared with ligation of pylorus and cannulation of pancreatic duct. After diversion of pancreatic juice began, pancreatic secretion including protein significantly increased, which coincided with a significant increase in plasma CCK-PZ concentration. The increases in both pancreatic secretion and plasma CCK-PZ were reversed by intraduodenal administration of bovine trypsin or rat pancreatic juice. Furthermore, the increase in pancreatic secretion was abolished by intravenous infusion of proglumide or an intravenous bolus injection of a rabbit anti-CCK-PZ serum, which also blocked clearly the increase in the pancreatic secretion stimulated by exogenous CCK-PZ8 (0.125 micrograms X kg-1 X h-1) in rats. Thus we conclude that the increase in pancreatic secretion resulting from elimination of pancreatic juice from the intestine is attributable, in part, to increased release of CCK-PZ, and thus it is suggested that trypsin in the intestinal lumen plays a significant role in release of CCK-PZ.     

Sequence of electrophysiological property and metabolic disorder in ischemic myocardium

The relationships of electrical changes to the time course of reduction in adenosine triphosphate (ATP) content were examined in 41 dogs with coronary artery ligation and 14 control dogs. Twenty dogs with malignant ventricular arrhythmias within 10 min of ischemia (VA dogs) were characterized by widening of the composite electrogram duration (147 +/- 47 msec at 5 min). In contrast, the composite electrogram duration was narrower (71 +/- 12 msec at 5 min, p less than 0.001) in 21 dogs without malignant arrhythmias (non-VA dogs). The degree of ATP reduction in VA dogs was significantly less at 3 min (3.11 +/- 0.28 mumol X g-1, p less than 0.05) and at 5 min (2.93 +/- 0.28 mumol X g-1, p less than 0.05) than in non-VA dogs (2.76 +/- 0.22 mumol X g-1, 2.39 +/- 0.44 mumol X g-1, respectively). The width of the electrograms in VA dogs decreased gradually after 10 min of ischemia, and it was not significantly different from non-VA dogs by 13 min, which coincided with disappearance of a difference in ATP content (2.10 +/- 0.34 mumol X g-1 and 2.35 +/- 0.23 mumol X g-1 in VA dogs and non-VA dogs biopsied at 10-20 min of ischemia). It was concluded that the metabolic deterioration in VA dogs advanced more slowly than that in non-VA dogs within 5 min of ischemia and the decrease in the width of the electrogram after 10 min did not result from a partial recovery of ischemia.     

Activation of proteases in cerulein-induced pancreatitis

The activation of zymogen proteases and lysosomal enzyme cathepsin B in the pancreas was investigated in cerulein-induced pancreatitis in rats. Acute pancreatitis was induced by two intraperitoneal injections of 40 micrograms/kg of body weight of cerulein at intervals of 1 h. After the first cerulein injection, the active trypsin and elastase contents in the pancreas tissues significantly increased, and reached the highest level at 3 h after the first injection, followed by peaks at 5 h in the serum amylase and lipase levels and the pancreas wet weight. Cathepsin B contents in pancreas tissues showed a parallel increase with active zymogen enzymes during the first 3 h of pancreatitis. These findings may suggest that the intracellular activation of trypsinogen is an important step in the development of cerulein-induced acute pancreatitis and that cathepsin B plays a role in the activation of trypsinogen in pancreatic acinar cells.     

Penetration of antibiotics into the pancreas in rats: an effect of acute necrotizing pancreatitis

BACKGROUND: Penetration of antibiotics into the pancreas is considered to be an important criterion in determining the most appropriate antibiotic treatment during severe acute pancreatitis. Our study investigated pancreatic penetration of five antibiotics in rats with and without acute necrotizing pancreatitis (ANP) (non-pancreatitis rats (NR), pancreatitis rats (AP)). METHODS: ANP was induced by intraductal bile acid injection, and 3 h later the antibiotic was administered. In both NR and AP the antibiotic concentrations were evaluated in blood and pancreatic tissue 90 min after antibiotic administration. RESULTS: The tissue/serum (T/S) ratios for NR were 16% with amikacin, 24% with amoxycillin/clavulanic acid, 27% with piperacillin, 59% with ofloxacin, and 108% with cefoperazone. The ratios for AP were 7%, 23%, 26%, 52%, and 70%, respectively. T/S ratios were similar for NR and AP except for amikacin, for which the T/S ratio was lower in AP than in NR (P = 0.02). Pancreatic tissue concentrations of antibiotics with high penetration rates (cefoperazone and ofloxacin) were sufficient to inhibit most of the pathogens expected during acute pancreatitis. The concentrations of the other antibiotics were less than the minimal inhibitory concentrations (MIC) for common potential pathogens in pancreatic infection. CONCLUSIONS: Cefoperazone and ofloxacin showed the best pancreatic penetration of the five antibiotics tested. The high concentrations of these antibiotics in the pancreatic tissue would have enabled efficient antibacterial activity against most of the potential pathogens causing pancreatic infection. An early stage of acute necrotizing pancreatitis did not have a major effect on the pancreatic concentrations of the antibiotics.     

Effects of somatostatin on acute canine experimental pancreatitits

Summary Somatostatin is an inhibitory hormone that decreases the secretion and end organ response of cholecystokinin (CCK). Inhibition of hormonal stimulation of pancreatic exocrine secretion by somatostatin may improve the course of acute pancreatitis. Anesthetized dogs underwent cholecystectomy and cannulation of the pancreatic duct, thoracic, duct, and portal vein. Twenty experiments were performed in random order with 5 dogs in each group. Hourly measurements of lymph flow and portal and thoracic duct amylase were made. Portal blood insulin, glucagon, and CCK concentrations were determined by radioimmunoassay on samples obtained at the beginning and end of the experiments. Pancreatitis was induced by injecting, under, constant pressure, 10 ml bile into the pancreatic duct during 1 min. Somatostatin was administered intravenously (20 μg/kg/hr). After 5 h, the dogs were killed, pancreas glands removed and weighted and tissue samples obtained for histologic evaluation. There was a significant-increase in lymph amylase output and portal venous amylase and CCK concentrations in the dogs with pancreatitis compared to the control dogs. In dogs with pancreatitis, lymphatic amylase secretion and portal CCK concentrations were significantly decreased by somatostatin. Somatostatin did not significantly alter portal amylase concentrations, pancreas gland weights or histologic inflammation when compared to values from dogs with pancreatitis not treated with somatostatin. In bile-induced acute experimental pancreatitis, somatostatin decreases thoracic duct amylase output and may have a protective influence on the course of pancreatitis.     

Oxidative stress. An early phenomenon characteristic of acute experimental pancreatitis.

Acute hemorrhagic pancreatitis was induced in Wistar rats using a retrograde intraductal injection of 5% Na-taurocholate. Rats were sacrificed at 1, 3, 6, and 24 h. Malondialdehyde and sulfhydryl groups concentration, as well as superoxide dismutase and catalase activity were measured in pancreatic, liver, and lung tissue. These parameters, with the exception of catalase, were also determined in serum and peritoneal exudate. Early and profound oxidative stress in each organ was evidenced by marked increases in malondialdehyde concentrations along with marked reductions in levels of sulfhydryl groups and superoxide dismutase; a paradoxical increase in catalase activity, perhaps compensatory, was noted in pancreas and lung. Survival for 24 h was associated with restoration of normality insofar as tissue malondialdehyde concentrations were concerned, but pancreas sulfhydryl groups remained markedly depleted. These data endorse the suggestion that the early provision of such compounds may help to accelerate recovery from hemorrhagic pancreatitis in humans.     

Influence of pancreatic surgery on gastric ulcers and somatostatin-like immunoreactivity in portal and aortic blood, and in the gastrointestinal tissues of the rat

Two weeks after pancreatic duct occlusion (OCC) or pancreatic half-resection (RES) in rats, the development of gastric ulcers was assessed. Somatostatin-like immunoreactivity (SLI) was measured simultaneously in portal and aortic blood as well as in fundic, antral, duodenal and pancreatic tissue specimens. Extracts of antral, duodenal and pancreatic tissue were chromatographed on a Sephadex G25 superfine column (1.6 +/- 90 cm) under strongly dissociating conditions. As compared to sham-operated controls (SHAM) ulcer index in arbitrary units (AU) and ulcer severity were significantly increased in duct-occluded rats (ulcer index: 5.6 +/- 1.9 AU in SHAM, 42.6 +/- 7.9 AU in OCC; severity: 0.47 +/- 0.37 mm in SHAM, 9.76 +/- 2.37 mm in OCC; p less than 0.001 respectively). Aortic SLI was increased in both experimental groups (SHAM: 53.2 +/- 7.4 pg/ml; RES: 110.9 +/- 16.6 pg/ml, p less than 0.01 vs SHAM; OCC: 96.0 +/- 9.0 pg/ml, p less than 0.001 vs SHAM); portal SLI was decreased in duct-occluded rats (SHAM: 88.9 +/- 7.1 pg/ml; OCC: 65.7 +/- 9.9 pg/ml; p less than 0.05). Tissue SLI was raised in the gastric fundus of duct-occluded rats (SHAM: 6.4/1.3-36.1 micrograms/g; OCC: 8.2/5.1-14.9 micrograms/g; p less than 0.05) and in the duodenum of resected animals (SHAM: 0.7/0.2-1.6 micrograms/g; RES: 1.4/0.4-2.3 micrograms/g; p less than 0.05), but decreased in the duct-occluded pancreas (SHAM: 3.7/1.0-8.2 micrograms/g; OCC: 2.1/0.5-5.6 micrograms/g; p less than 0.05). In all three groups, the major part of total SLI in antrum, duodenum and pancreas was identical with somatostatin-14 at gel chromatography.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of naloxone on the haemodynamics and the outcome of experimental acute pancreatitis in dogs

Endogenous opioid peptides may play a role in the genesis of pancreatic damage in acute pancreatitis. The effects of naloxone on the haemodynamic changes in acute pancreatitis were investigated by inducing it in dogs with pancreatic ductal injection of fresh trypsin-bile mixture. In the control group (n = 8), acute pancreatitis was characterized haemodynamically by falls in the maximum positive and negative dP/dt (+/- dP/dt), cardiac output (CO) and cardiac index (CI), and increases in the pulmonary vascular resistance (PVR) and systemic vascular resistance (SVR) as well as an early reduction of pancreatic blood flow (PBF). In another set of eight dogs (naloxone group), naloxone was given intravenously 10 min after the induction of acute pancreatitis (80 micrograms/kg as a bolus + 80 micrograms/kg/h for 3 h). Compared with untreated dogs, naloxone significantly increased PBF and the +/- dP/dtmax; prevented the significant decreases in CO and CI and increases in PVR and SVR, and reduced significantly the severity of pancreatitis, as assessed by both the histological staging and the mortality rate. These results suggest that naloxone limits the progression of acute pancreatitis from oedematous to haemorrhagic form. It is proposed that endogenous opioid peptides may play a role in the pathophysiology of acute pancreatitis.     

大鼠急性胰腺炎模型建立的探究

目的 建立一种简单易行和稳定可靠的L-精氨酸诱导的急性胰腺炎模型,以便对治疗急性胰腺炎的疗效进行观察和探讨.方法 选择36只健康SD大鼠,采用15％和20％不同浓度的L-精氨酸溶液（用0.9％的生理盐水配制而成）1.5 g/kg腹腔内注射入大鼠体内,分别于不同的时间点取材,分别检测大鼠的存活率、血生化指标中的血清淀粉酶和脂肪酶以及大鼠胰腺的病理变化.结果 15％L-精氨酸溶液腹腔注射大鼠的生存率明显高于20％组,实验组的动物12h后血清淀粉酶和血清脂肪酶水平明显升高,显著高于对照组（P ＜0.0001）,但两实验组之间差异无统计学意义（P＞0.05）,病理结果显示胰腺腺泡结构紊乱,大量腺泡细胞水肿、坏死,出现核固缩,胞内空泡形成,小叶间隙增宽并伴有炎性细胞浸润及出血.20％L-精氨酸组病理改变较严重,腺泡和导管消失并伴有皂化斑形成.结论 应用15％ ～ 20％的L-精氨酸溶液1.5 g/kg的剂量可致不同程度的比较稳定的急性胰腺炎模型.并且其浓度大小决定胰腺损伤的程度.15％L-精氨酸所致急性胰腺炎是比较理想的模型.