Course Of Acute Experimental Pancreatitis Research Articles

Azithromycin does not improve disease severity in acute experimental pancreatitis.

Acute pancreatitis is a severe systemic disease triggered by a sterile inflammation and initial local tissue damage of the pancreas. Immune cells infiltrating into the pancreas are main mediators of acute pancreatitis pathogenesis. In addition to their antimicrobial potency, macrolides possess anti-inflammatory and immunomodulatory properties which are routinely used in patients with chronic airway infections and might also beneficial in the treatment of acute lung injury. We here tested the hypothesis that the macrolide antibiotic azithromycin can improve the course of acute experimental pancreatitis via ameliorating the damage imposed by sterile inflammation, and could be used as a disease specific therapy. However, our data show that azithromycin does not have influence on caerulein induced acute pancreatitis in terms of reduction of organ damage, and disease severity. Furthermore Infiltration of immune cells into the pancreas or the lungs was not attenuated by azithromycin as compared to controls or ampicillin treated animals with acute experimental pancreatitis. We conclude that in the chosen model, azithromycin does not have any beneficial effects and that its immunomodulatory properties cannot be used to decrease disease severity in the model of caerulein-induced pancreatitis in mice.

EFFECT OF BOUGINAGE AND WASHING OF THE PANCREATIC DUCT ON THE COURSE OF EXPERIMENTAL ACUTE PANCREATITIS

The presence of many hypotheses of the development of acute pancreatitis such as pancreatic duct hypertension, pancreatic reflux, vascular, allergic, neuro-reflex, infectious, etc. confirm the lack of a clear understanding of the development mechanisms of this pathology, and hence inaccuracy in the treatment and negative consequences. The purpose of this study was to investigate the effect of bouginage and flushing of the pancreatic duct on the course of experimental acute pancreatitis. Experiments were carried out on 12 dogs, for which a model of pancreatitis was created by autobile administration into the pancreas duct. Animals were divided into four groups, 3 animals per each, with the term of deduce from the test in one, three, seven days and six months respectively. Before the pancreas duct perfusion, it was injected with polyvinylchloride bougie that was removed through the incision in the distal part of the pancreas duct. Such manipulation allowed to conduct duct washing with medicinal substances at a pressure of 0.49-0.6 kPa and confirmed the assumption that in acute pancreatitis, filling of pancreas duct with condensed protein masses was observed, and this, changes the approach not only to the establishment of the pathogenetic link in the process of acute pancreatitis development, but also to its treatment. The duct was washed once. The common comprehensive drug therapy was carried out in dogs within the next five, six days. At the end of the first day, out of the 12 dogs, nine stood independently, the rest - on the second day. On the third day, all animals drank water, responded to stimuli. On the fifth day they were active, taking liquid feed. On the seventh day on their behavior and feeding manner the dogs of this group did not differ from healthy ones. To study morphological changes in pancreas after duct washing, three dogs were withdrawn from the test in one day. At autopsy effusion in peritoneal cavity was not observed. The left lobe of pancreas was a little bit shorter. Place of dissection of the tissues of the pancreas and the duct is covered with a blood clot. In the area of duodenum dissection, isolated patches of steatoenecrosis retained. Microscopically, in the duct area dissection changes in pancreas tissues, in general, were the same as in duct dissection without perfusion. At the same time, the plethora for this term was great. Necrotic centers of parenchyma were isolated and with moderate neutrophilic infiltration. Distant from the dissection zone in pancreas tissues there were minor focal hemorrhages with a violation of its structure, however, hyperplasia, foci of neutrophilic infiltration of the interstitial connective tissue were less manifestated. In the proximal part of the duct, the pancreas tissue retained moderate plethora. In addition, there were small foci of hemorrhages with a violation of the structure of individual acinus and slight neutrophilic infiltration in interstitial connective tissue. The latter was also marked by the accumulation of macrophages and the proliferation of fibroblasts, there were isolated areas of hemorrhages. In intact part there was an insignificant edema of interstitial connective tissue. As a result of the conducted experiments, we were convinced of the effectiveness of this method of treating acute pancreatitis.

Role of phosphoinositide 3-kinase in the pathogenesis of acute pancreatitis.

A large body of experimental and clinical data supports the notion that inflammation in acute pancreatitis has a crucial role in the pathogenesis of local and systemic damage and is a major determinant of clinical severity. Thus, research has recently focused on molecules that can regulate the inflammatory processes, such as phosphoinositide 3-kinases (PI3Ks), a family of lipid and protein kinases involved in intracellular signal transduction. Studies using genetic ablation or pharmacologic inhibitors of different PI3K isoforms, in particular the class I PI3Kδ and PI3Kγ, have contributed to a greater understanding of the roles of these kinases in the modulation of inflammatory and immune responses. Recent data suggest that PI3Ks are also involved in the pathogenesis of acute pancreatitis. Activation of the PI3K signaling pathway, and in particular of the class IB PI3Kγ isoform, has a significant role in those events which are necessary for the initiation of acute pancreatic injury, namely calcium signaling alteration, trypsinogen activation, and nuclear factor-κB transcription. Moreover, PI3Kγ is instrumental in modulating acinar cell apoptosis, and regulating local neutrophil infiltration and systemic inflammatory responses during the course of experimental acute pancreatitis. The availability of PI3K inhibitors selective for specific isoforms may provide new valuable therapeutic strategies to improve the clinical course of this disease. This article presents a brief summary of PI3K structure and function, and highlights recent advances that implicate PI3Ks in the pathogenesis of acute pancreatitis.

Effect of magnesium supplementation and depletion on the onset and course of acute experimental pancreatitis

Background and objectiveHigh calcium concentrations are an established risk factor for pancreatitis. We have investigated whether increasing magnesium concentrations affect pathological calcium signals and premature protease activation in pancreatic acini,...

Effects of Pantoprazole in experimental acute pancreatitis

Aims Oxidative stress with free radicals plays a crucial role in acute pancreatitis (AP). Pantoprazole (PPZ), widely used as a proton pump inhibitor, possesses reactivity towards hydroxyl radicals. The aim of the study was to examine the effect of PPZ on the course of experimental AP. Main methods Mild AP was induced in rats by caerulein (n = 12). Severe AP was induced by infusion of glycodeoxycholic acid (10 mM) into the pancreatic duct combined with caerulein (n = 12). Both AP models were randomized to PPZ treatment (20 mg/kg at baseline and after 12 h) or placebo. Control animals received Ringer solution (n = 6) without AP induction. After 24 h severity of AP was examined by histology, enzyme levels, edema and inflammatory markers (myeloperoxidase, protein profiling). Furthermore, CD62P and CD31 for leukocyte and platelet activation were investigated. Key findings Histology showed that PPZ treatment reduced tissue infiltration of inflammatory cells and acinar cell necrosis in severe AP. After PPZ treatment CD62P expression in mild AP and CD31 expression in severe pancreatitis decreased, indicating an inhibition of platelet activation. In mild and severe AP, PPZ significantly decreased amylase, LDH, edema and myeloperoxidase activity. Protein profile of pancreatic juice and serum revealed different spectra and less pancreatic juice proteins in PPZ treated groups indicating less acinar cell leakage. Significance PPZ possesses anti-inflammatory in vivo properties and attenuates the course of AP. This is mediated via a reduced expression of inflammatory and adhesive proteins with a consecutive decrease in platelet and leukocyte activation as key steps in the pathogenesis of AP.

The calcium binding protein S100A9 is essential for pancreatic leukocyte infiltration and induces disruption of cell–cell contacts

Leukocyte infiltration is an early and critical event in the development of acute pancreatitis. However, the mechanism of leukocyte transmigration into the pancreas and the function of leukocytes in initiating acute pancreatitis are still poorly understood. Here, we studied the role of S100A9 (MRP14), a calcium binding protein specifically released by polymorph nuclear leukocytes (PMN), in the course of acute experimental pancreatitis. Acute pancreatitis was induced by repeated supramaximal caerulein injections in S100A9 deficient or S100A9 wild-type mice. We then determined S100A9 expression, trypsinogen activation peptide (TAP) levels, serum amylase and lipase activities, and tissue myeloperoxidase (MPO) activity. Cell-cell contact dissociation was analyzed in vitro with biovolume measurements of isolated acini after incubation with purified S100A8/A9 heterodimers, and in vivo as measurement of Evans Blue extravasation after intravenous application of S100A8/A9. Pancreatitis induced increased levels of S100A9 in the pancreas. However, infiltration of leukocytes and MPO activity in the lungs and pancreas during acute pancreatitis was decreased in S100A9-deficient mice and associated with significantly lower serum amylase and lipase activities as well as reduced intrapancreatic TAP-levels. Incubation of isolated pancreatic acini with purified S100A8/A9-heterodimers resulted in a rapid dissociation of acinar cell-cell contacts which was highly calcium-dependent. Consistent with these findings, in vivo application of S100A8/A9 in mice was in itself sufficient to induce pancreatic cell-cell contract dissociation as indicated by Evans Blue extravasation. These data show that the degree of intrapancreatic trypsinogen activation is influenced by the extent of leukocyte infiltration into the pancreas which, in turn, depends on the presence of S100A9 that is secreted from PMN. S100A9 directly affects leukocyte tissue invasion and mediates cell contact dissociation via its calcium binding properties.

ETANERCEPT ATTENUATES THE DEVELOPMENT OF CERULEIN-INDUCED ACUTE PANCREATITIS IN MICE

TNF-alpha plays a pivotal role in the pathogenesis of acute pancreatitis. Recent studies have shown that TNF-alpha inhibition significantly ameliorates the course of experimental acute pancreatitis, but in this context, the effects of Etanercept, a novel anti-TNF-alpha agent, have not been investigated so far. The aims of the present study are (i) to assess the effects of pharmacological inhibition of TNF-alpha by means of Etanercept on the inflammatory response and apoptosis in a murine model of necrotizing acute pancreatitis and (ii) to compare the results to those observed in TNF-alpha receptor 1 knockout (TNFR1-KO) mice. Necrotizing acute pancreatitis was induced in TNF-alpha wild type for TNFR1 (WT) and TNFR1-KO mice by intraperitoneal injection of cerulein (hourly x5, 50 microg/kg). In another group of WT mice, Etanercept was administered (5 or 10 mg/kg, s.c.) at 1 h after first cerulein injection. Control groups received saline treatment. After 24 h, biochemical, histological, and immunohistochemical evidences of acute pancreatitis developed in all cerulein-treated mice; apoptosis was also present in the pancreas. Contrarily, pancreatitis histological features, amylase and lipase levels, pancreas water content, and myeloperoxidase activity were reduced in a similar degree in Etanercept-treated and TNFR1-KO mice. Likewise, in these two groups, immunohistochemical stainings and terminal deoxynucleotidyltransferase-mediated UTP nick-end labeling assay were found negative. TNF-alpha receptor 1 gene deletion and Etanercept administration ameliorate the course of experimental acute pancreatitis in a similar degree. Future studies on clinical applications of Etanercept in pancreatitis seem promising.

Clusterin is protective in pancreatitis through anti-apoptotic and anti-inflammatory properties

Clusterin is overexpressed in pancreas during the acute phase of pancreatitis. We intended to clarify the role of clusterin expression in stressed exocrine pancreas. We performed in vitro experiments in transfected AR4-2J cells with modified expression levels of clusterin and in vivo studies in clusterin-deficient mice. AR4-2J cells were exposed to agents mimicking cell-stress during pancreatitis (cerulein, hydrogen peroxide, staurosporine or lysophosphatidylcholine). Clusterin-overexpressing AR4-2J cells showed higher viability after cell stress and accordingly reduced rates of apoptosis and lessened caspase-3 activation. Blockage of endogenous clusterin expression reduced viability and enhanced apoptosis. Presence of clusterin reduced NF-κB activation and expression of the NF-κB target genes TNF-α and MOB-1 under cell stress. Clusterin-deficient mice showed a more severe course of acute experimental pancreatitis with enhanced rates of apoptosis and inflammatory cell infiltration. We concluded that clusterin was protective during inflammation of exocrine pancreas because of its anti-apoptotic and anti-inflammatory functions.

Modification of intestinal flora with multispecies probiotics reduces bacterial translocation and improves clinical course in a rat model of acute pancreatitis

Infection of pancreatic necrosis by gut bacteria is a major cause of morbidity and mortality in patients with severe acute pancreatitis. Use of prophylactic antibiotics remains controversial. The aim of this experiment was assess if modification of intestinal flora with specifically designed multispecies probiotics reduces bacterial translocation or improves outcome in a rat model of acute pancreatitis. Male Sprague-Dawley rats were allocated into 3 groups: (1) controls (sham-operated, no treatment), (2) pancreatitis and placebo, and (3) pancreatitis and probiotics. Acute pancreatitis was induced by intraductal glycodeoxycholate and intravenous cerulein infusion. Daily probiotics or placebo was administered intragastrically from 5 days prior until 7 days after induction of pancreatitis. Tissue and fluid samples were collected for microbiologic and quantitative real-time PCR analysis of bacterial translocation. Probiotics reduced duodenal bacterial overgrowth of potential pathogens (Log(10) colony-forming units [CFU]/g 5.0 +/- 0.7 [placebo] vs 3.5 +/- 0.3 CFU/g [probiotics], P < .05), resulting in reduced bacterial translocation to extraintestinal sites, including the pancreas (5.38 +/- 1.0 CFU/g [placebo] vs 3.1 +/- 0.5 CFU/g [probiotics], P < .05). Accordingly, health scores were better and late phase mortality was reduced: 27% (4/15, placebo) versus 0% (0/13, probiotics), respectively, P < .05. This experiment supports the hypothesis that modification of intestinal flora with multispecies probiotics results in reduced bacterial translocation, morbidity, and mortality in the course of experimental acute pancreatitis.

MULTISPECIES PROBIOTICS ABOLISH ACUTE PANCREATITIS-ASSOCIATED MUCOSAL BARRIER FAILURE IN MURINE ILEUM

Intestinal mucosal barrier failure during acute pancreatitis is associated with translocation of luminal bacteria to extra-intestinal sites. Resulting infectious complications are a major cause of morbidity and mortality. Aim of this study was to determine if multispecies probiotics can diminish mucosal barrier failure in the course of experimental acute pancreatitis (AP). Mice were treated daily with a mixture of six probiotic strains (Ecologic 641®, Winclove BioIndustries, Amsterdam, The Netherlands, 2.5×109 bacteria/oral gavage) or placebo, from 2 days prior to cerulein induced AP (hourly intraperitoneal injections, 50μg/kg, for 10 hours) until termination 72 hours after the first injection. Sham procedure consisted of 10 hourly sterile saline injections, without probiotic or placebo treatment. Mucosal barrier function of the distal ileum was assessed by measurement of mucosal integrity (electrical resistance, R: Ω.cm2) and permeability (steady state transepithelial flux of 0.01 gr/l Na-fluorescin, flux: ng/cm2/h) at 36°C, in Ussing chambers. AP reduced mucosal integrity and increased permeability (AP (n = 13) vs. sham (n = 15): R = 28.1 ± 1.4 Ω.cm2 (mean ± SEM) vs. 37,5 ± 1.7, P = 0.002; flux = 400 ± 48 ng/cm2/h vs. 189 ± 18, P = 0.001, ANOVA). Probiotic treatment completely abolished the AP-induced mucosal barrier failure (placebo vs. probiotics (n = 15): R = 26.4 ± 2.6 vs. 34.9 ± 1.8, P = 0.003; flux = 427 ± 62 vs. 246 ± 32, P = 0.014). Mucosal resistance and permeability of probiotic treated mice were not different from those of healthy controls or sham (P = 0.551 and P = 0.194, respectively). Conclusions: Experimental acute pancreatitis results in decreased integrity and increased permeability of ileal mucosa. This mucosal barrier failure can be abolished by the used regime of selected multispecies probiotics. Support of mucosal barrier function by multispecies probiotics may provide a novel strategy to reduce infectious complications during acute pancreatitis.

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

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. 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. 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. 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. 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.

Effects of prophylactic magnesium treatment on the onset and course of acute experimental pancreatitis

Effects of prophylactic magnesium treatment on the onset and course of acute experimental pancreatitis

The expression of cellular adhesion molecules is upregulated and co-localized with the oxidative stress in the early course of experimental acute pancreatitis

Using a novel method to demonstrate histologically the production of oxygen free radicals (OFR-s), this study investigates the possible role of cellular adhesion molecules (CAM-s) -in relation to the oxidative stressduring the early course of acute necrotizing pancreatitis (ANP). Similarly to other inflammatory pathologies, injury to the pancreatic acini supposedly results in the expression/upregulation of CAM-s on the periacinar endothelial cells as well as release of proinflammatory mediators. The adherent lenkocytes, mostly neutrophils (PMN), become activated and release OFR-s, microbicidal enzymes and more mediators to strengthen the inflammatory response. An uncontrolled inflammatory cascade may become locally and systemically deleterious. We have developed a novel technique to detect the presence and localization of OFR-s in vivo, using the cerium capture method. Reaction of OFR-s with CeC13 leads to cerium-perhydroxide precipitation. These deposits can be detected histologically by their laser reflecting properties using confocal laser scanning microscopy (CLSM) in the reflectance mode (RM). METHODS: ANP was induced in Wistar rats by retrograde infusion of taurocholate into the pancreatic duct. At different time points (1, 2, 24h) the animals were re-laparotomized and perfused with CeC13 (20mM in Hartmann solution) through the abdominal aorta, then sacrificed. Normal rats received a CeCI 3 perfusion in the same fashion and were used as controls. Pancreata were snap frozen in liquid nitrogen. Indirect immunofluorescence (FITC fluorochrome) was performed on serial frozen sections to label E-selectin, P-selectin, ICAM-1, VCAM-1, and PECAM molecules. Nuclei were colored by propidium-iodide. Simultaneous observation of CAM expression, cerium reflectance and cell type definition was performed by CLSM using multichannel detection. RESULTS: The capillaries in the pancreata of normal animals showed weak, sparse P-selectin and ICAM-1 positivity, with a constitutive expression of PECAM. Reflectance signals were negligible. At the early time points (1, 2h) of pancreatitis the tissue architecture was found to be relatively well preserved, an increase in endothelial P-selectin, and ICAM-1 immunoreactivity was observed. Strong, shining reflectance could be detected in the pancreatic microvasculature, as well as cloud-like signals over certain groups of acini. Numerous leukocytes adherent to CAM positive capillary walls were seen, however they presented small, focal, mostly intracellular reflectance signals, which were often localized at the contact points between the CAM-s and leukocytes. At 24h the samples were characterized by intense PMN infiltration, heterogeneous necrosis, strong, mostly perinecrotic P-selectin, and ICAM-1, but moderately increased E-selectin, and VCAM-1 expression. Large numbers of adherent, or already transmigrated PMN-s showed abundant intraand pericellular reflectance signals. CONCLUSION: Pancreatic endothelial CAM-s are upregulated early in ANP, and may play a role -in addition to cytokinesin the activation of adhering leukocytes. At the earliest time points the major source of OFR seems to be the pancreatic cell (xanthine-oxidase), later the activated PMN-s, thereby possibly contributing to local and distant organ damage. The CAM over-expression showed a significant spatial co-localization with the oxidative stress. The work of G. Telek was supported by a grant from IRMAD Foundation, France.

Influence of glutathione synthesis on the course of acute experimental pancreatitis in the rat

Introduction: Glutathione plays a central role as scavenger of reactive oxidative metabolites. L-Buthioninsulfoximine (BSO) is therefore, as inhibitor of /-glutamylcystein-synthetase and by the way of glutathione synthesis, a potent amplifier of oxidative stress. We investigated the influence of BSO on the experimentally induced cerulein pancreatitis of the rat and on the cerulein stimulation of isolated pancreatic acini as correlate to oxidative stress. Methods: Male Wistar rats had a bolus of 1 ml 0,9% NaC1 with or wihtout (control) 8 pmol/kg KG BSO injected intravenously. After anesthesia with ketanest/pentobarbital, an acute pancreatitis was induced by time and pressure dependent intraductal infusion of 0,125 ml 10 mMol glucodesoxychollic acid (GDOC) and subsequent intravenous application of 5 pg/kg/h cerulein. After a maximum observation period of 24 hrs the rats were euthanasised and the pancreas removed for histological analysis. For preparation of isolated pancreatic acini, male Wistar rats had their pancreas removed and collagenase digested in a standardised fashion. Isolated acini were stimulated over 45 Minuten with declining concentrations of cerulein (10 -7 to 10 -12 M). Lipase and Amylase were measured in the supernatant. Results: L-Buthioninsulfoximin (BSO) significantly increased mortality in experimentally induced pancreatitis. 7 of 8 BSO animals died versus 0 of 6 controls (p=0,036, Mann-Whitney-U-Test). On cellular level, BSO reduced secretory activity of stimulated acini concerning amylase as well as lipase (p < 0,01 with each; paired t-test). Conclusion: BSO increases mortality in experimentally induced pancreatitis. This is probably due to early local and systemic decompensation glutathionedependent scavenging systems. On cellular level, this mechanism is probably valid through reduction of energy dependent transport under oxidative stress (cerulein).

Influence of thyrotropin-releasing hormone on experimental pancreatitis in rats.

The main purpose of this study was to investigate the influence of thyroid releasing hormone on acute sodium-taurocholate-induced pancreatitis in rats. Thyroid-releasing hormone did not change the survival rate, serum amylase, glucose calcium, liver transaminases levels or the degree of pancreatic damage, but reduced lactate dehydrogenase. Our findings suggest that the use of thyroid-releasing hormone has no beneficial effect on the course of acute experimental pancreatitis.

The influence of early total parenteral nutrition on experimental pancreatitis in rats.

The main purpose of this study was to investigate the influence of early total parenteral nutrition on acute sodium-taurocholate-induced pancreatitis in rats. Total parenteral nutrition did not change the survival rate, serum amylase, calcium or liver transaminase level on the degree of pancreatic damage, but reduced serum acid phosphatase and lactate dehydrogenase levels. Hyperglycemia occurred during the use of total parenteral nutrition. Total parenteral nutrition is not harmful in the course of acute experimental pancreatitis, and could be used with few side effects.

Fasting prevents acute pancreatitis induced by cerulein in rats

We examined the effect of fasting on the course of experimental acute pancreatitis induced in rats by four subcutaneous injections of 20 micrograms/kg body weight of cerulein at hourly intervals. Rats were either fasted from 24 hr before to 9 hr after the first cerulein injection or fed ad libitum throughout the experiment. Twenty-four hours of fasting reduced cerulein-induced increases in serum levels of amylase and anionic trypsin(ogen) to 50 and 70% of those in fed rats, respectively. Increases in pancreatic wet weight after cerulein injections were also less in fasted rats than in fed rats. Pancreatic content of trypsin was significantly decreased after a 24-hr fast, and no further changes were induced by cerulein injections. The histological signs of acute pancreatitis were greatly alleviated by fasting. However, 24 hr of fasting did not alter the sensitivity and responsiveness of the exocrine pancreas to cerulein in both in vivo and in vitro. Plasma CCK bioactivity and immunoreactive secretin concentration in 24-hr-fasted rats were significantly lower than those in fed rats. Administration of CCK receptor antagonist, loxiglumide, 12 hr prior to the induction of acute pancreatitis reduced the increase in serum amylase activity in fed rats to nearly the same levels as that in fasted rats and alleviated histological signs of pancreatitis to some extent. These present observations suggest that fasting lessens the severity of cerulein-induced acute pancreatitis by reducing endogenous CCK release.

Effect on hemodynamics of therapeutic infusion of gabexate mesilate (FOY) in experimental acute pancreatitis

Acute pancreatitis was induced in ten anesthetized dogs by retrograde injection for bile mixed with trypsin into the pancreatic duct. Five animals were treated with i.v. infusion of gabexate mesilate in a dose of 1 mg/kg per hour. Hemodynamic data were regulary monitored during a 10-h observation period. Cardiac output (CO), mean arterial pressure (MAP), and left ventricular stroke volume (LVSV) decreased rapidly in untreated animals. An increase of systemic vascular resistance (SVR) and pulmonary vascular resistance (PVR) was observed in dogs without treatment. Gabexate mesilate given as a therapy significantly improved the hemodynamic parameters. The study demonstrates an advantageous influence of synthetic antiprotease gabexate mesilate on the course of acute experimental pancreatitis.

Functional state of the histamine-histaminase system in the course of experimental acute pancreatitis

The role of neurohumoral factors and hormones in the pathogenesis of many diseases and, in particular, of inflammatory processes, is evident. When analyzing the role of serotoninergic structures [1], of the sympathicoadrenal complex [3], and of steroid hormones [2] in these processes, we were naturally interested in the degree of participation of the histamine-histaminase system in an inflammatory process in the pancreas. The role of histamine as the local mediator of inflammation has been a topic for discussion for a long time. Numerous investigations have shown that histamine may be one of the chief mediators in the early stages of inflammation. It activates the vascular endothelium locally for taking up colloidal particles. The neutralizing effect of antihistamines confirms the specific role of histamine in the inflammatory process.

Blood rheology and microcirculation in the course of acute experimental pancreatitis

The results of the experiments performed on 63 rabbits with experimentally induced acute pancreatitis made it possible to conclude that this pathology was accompanied by considerable hemorheological and microcirculatory disorders. The degree of hemorheological deviations was shown to correlate with the severity of acute pancreatitis.