Organ Failure In Acute Pancreatitis Research Articles

Low Serum Adiponectin Levels Are Associated With Systemic Organ Failure in Acute Pancreatitis

Obesity markedly increases the risk of severe acute pancreatitis (SAP), possibly through the action of adipokines. We tested the hypothesis that serum adiponectin, the primary anti-inflammatory adipokine, is associated with functional polymorphisms in the adiponectin gene (ADIPOQ) and inversely associated with SAP. Severe AP was defined as the presence of remote organ failure. ADIPOQ polymorphisms rs2241766T>G and rs1501299G>T were evaluated by DNA sequencing. Serum samples were assayed using a Luminex assay (Luminex, Austin, Tex). One hundred thirty-three patients with AP and 94 healthy controls were ascertained. Adiponectin levels were measured in 60 patients with early serum samples (27 patients with mild AP and 33 patients with SAP). Adiponectin levels from days 1 to 3 were inversely correlated with body mass index (BMI) (rho = -0.49; P = 0.002) and were significantly lower for patients with SAP (median, 3.74 microg/mL) than those with mild AP (6.58 microg/mL; P = 0.02). Neither ADIPOQ polymorphism affected susceptibility to or severity of AP. A receiver operating characteristics curve using adiponectin levels as the severity predictor provided an area under the curve of 0.75. Serum adiponectin levels in patients with AP are inversely correlated with BMI and organ dysfunction. Further studies are needed to determine whether adiponectin is a marker of low BMI or if it provides significant protection from SAP.

Recent Developments in Acute Pancreatitis

The incidence of acute pancreatitis (AP) has been increasing worldwide, but the major etiologies remain gallstones and alcohol. Several studies have reported that smoking is an independent risk factor for developing AP. Classification of AP has traditionally used the categories of mild and severe disease. However, a new intermediate category of moderately severe AP has been described with intermediate characteristics including a high incidence of local complications but a low mortality. Assessment criteria that can serve as early predictors of AP severity are often complex and not sufficiently accurate. However, several recently described criteria that rely on criteria such as the body mass index, physical findings, and simple laboratory measurements could prove useful if validated in large prospective studies. Many issues related to the therapy of AP are still unresolved. Although preliminary studies support the importance of early volume expansion for the treatment of acute pancreatitis, optimization of the amount and type of fluids will require further studies. Similarly, preliminary studies suggest that enteral nutrition might benefit patients with AP and could even be useful early in the course of disease. However, the timing and type of fluids as well as the intestinal infusion site require further study. Finally, issues related to the prophylactic use of antibiotics in patients with severe AP have not been resolved. While the process of clinical investigation moves slowly, progress has been made in clinical studies of AP.

M1269 Lack of Aggressive Early Fluid Resuscitation Is Associated with Organ Failure in Acute Pancreatitis

pancreatitis, we investigated the expression of HO-1 in patients with pancreatitis as compared to patients with non-pancreatic disease and healthy volunteers. Methods: 18 patients (4 with non pancreatic disease and 14 with pancreatitis) and 8 normal healthy controls of similar age and gender were recruited. Blood was drawn early during admission (day1) and 48 h later (day3). Peripheral blood mononuclear cells (PBMC) were isolated and HO-1 levels were assessed by flow cytometry (FACS) and western blotting (WB). HO-1 mean fluorescence intensity (MFI) was normalized to standardized beads to allow for FACS comparison between samples processed at different days. Isolated PBMCs were cultured for 24 and 48 h in the absence or presence of hemin to assess inducibility of HO-1. Results: MFI corresponding to HO-1 expression was highest in circulating neutrophils and monocytes as determined by FACS. Patients with acute pancreatitis had the highest levels of HO-1 expression at day1 (7709+/-1193; arbitrary units) as compared to patients with non-pancreatitis (3795+/-1305; p<0.05) and healthy controls (3758+/-613; p=0.01). Furthermore, day3 HO-1 levels in patients with acute pancreatitis decreased with clinical improvement, whereas samples from non-pancreatitis patients and healthy volunteers either increased slightly or remained unchanged. Culturing of PBMC isolated from patients with acute pancreatitis, followed by induction with hemin, leads to a marked further up-regulation of HO-1. In contrast, PBMC from healthy volunteers are less responsive to hemin-mediated HO-1 induction. Conclusions: (i) pancreatitis leads to reversible up-regulation of HO-1 in PBMC during the acute phase that correlates with clinical improvement, and involves primarily monocytes and neutrophils; (ii) PBMC from acutely ill patients with pancreatitis appear to be primed to HO-1 induction by hemin, which implies that administration of heminmay offer a beneficial therapeutic effect.

ELEVATED SERUM LEVEL OF THE COMPLEMENT REGULATOR PROTEIN CD59 IS A PREDICTOR OF ORGAN FAILURE IN ACUTE PANCREATITIS

Introduction: Complement activation has been shown in the plasma of patients with acute pancreatitis (AP). CD59 is a small protein that down-regulates activation of complement. In this study, we analysed AP patients during the first week after admission, for the serum levels of the complement membrane regulator protein CD59. The main aim was to determine whether release of soluble CD59 could predict the development of organ failure in AP. Methods: Thirty-nine patients with AP admitted to Helsinki University Central Hospital were included into the study. Patients were retrospectively categorised into those with mild AP (grade 0) or severe AP according to Atlanta classification. Patients with severe AP were further subcategorised into those who had only local complications and who recovered without organ dysfunction (grade 1), and into those who developed organ dysfunction (grade 2). Thirteen patients with grade 0, 14 with grade 1 and 12 with grade 2 attacks were included. The patients with organ dysfunction (grade 2) were compared to patients without organ dysfunction (grade 0 and 1). Blood samples were collected at admission and on days 1 and 3-7 post admission. CD59 levels were measured by a sandwich enzymeimmunoassay. Mann-Whitney U-test was used for comparison between the groups. The values for C-reactive protein (CRP) and APACHE II scores were also collected. Results: At admission, the serum CD59 concentration was significantly higher (p = 0.002) in grade 2 patients (median 104.2, range 26.1-186.3) than in grade 0 and 1 patients (median 37.3, range 30.3-75.9 and median 38.6, range 19.9-96.1). The serum CD59 concentration remained also significantly higher in grade 2 patients than in grade 0 and 1 patients during the hospitalisation on days 1 and 3-7 (p = 0.001 and p = 0.002). Also, the overall serum CD59 concentrations were significantly higher in patients with organ dysfunction (p < 0.001) than in patients without organ dysfunction. The CD59 levels of all patients were found to correlate significantly (p < 0.05) with CRP levels and APACHE II scores on admission (R = 0.401 and R = 0.321, respectively) and on day 1 (for CRP R = 0.372, p < 0.05 and for APACHE II scores R = 0.523, p = 0.01). A significant correlation with CRP and CD59 was found also during the hospitalisation on days 3-7 (R = 0.383, p < 0.05). Conclusion: Elevated serum levels of complement regulator protein CD59 seem to predict organ failure in severe AP.

Organ failure in acute pancreatitis

Organ failure in acute pancreatitis

Role of serum endotoxin and antiendotoxin core antibody levels in predicting the development of multiple organ failure in acute pancreatitis.

It has been proposed that endotoxin contributes to the development of multiple organ failure (MOF) in acute pancreatitis. Endotoxaemia is transient and may not be detected by intermittent blood sampling. By contrast, not only can changes in the patient's endogenous antiendotoxin core antibody pool persist for many days, but depletion of this pool may be a key event in determining the physiological significance of endotoxaemia. A series of 33 patients with acute pancreatitis had daily measurement of Acute Physiology Score (APS) and levels of C-reactive protein, interleukin 6, endotoxin, immunoglobulin (Ig) G and IgM antiendotoxin core antibodies, and prospective documentation of complications. Endotoxin was detected in the serum of 13 patients, while a significant change in levels of endogenous antiendotoxin core antibodies was detected in all those with severe pancreatitis and in 28 overall. MOF developed in seven patients, five of whom died. The combination of a rising APS over the first 48 h of admission and a significant fall in endogenous IgG antibody level was observed in all patients who developed MOF (seven of seven), but in only one of 16 without MOF (P = 0.00003; overall predictive value 91 per cent). This study suggests that measuring the initial trend in APS and the concentration of endogenous IgG antiendotoxin core antibody provides a means of identifying patients with acute severe pancreatitis who are at high risk of developing MOF. This group might benefit from passive immunotherapy with antiendotoxin antibodies.

Impact of chronic and acute high‐fat feeding on acute experimental pancreatitis complicated by endotoxinaemia

Background: Obesity is associated with increased severity in patients with acute pancreatitis (AP). The underlying mechanisms are unknown. Genetically obese rats exhibit decreased survival rate in experimental AP, but the clinical relevance of this model of obesity may be questioned. It is proposed that development of organ failure in AP occurs in two stages: initial priming of leucocytes followed by a second inflammatory attack. The aim was to evaluate the impact of diet‐induced obesity on outcome in a ‘two‐hit’ model of AP. Methods: Lipopolysaccharide (LPS) was injected i.p. 3 h after retrograde bile duct infusion of sodium taurocholate in rats. Three experiments were done: 1) an LPS dose‐response experiment, 2) chronic high‐fat feeding (HF) for 16 weeks, and 3) acute HF for 10 days. Control rats received normal chow. Obesity, morphology and survival rate were assessed. Results: LPS dose‐dependently decreased survival rate and increased morphological severity. HF increased weight, intra‐abdominal and liver fat. Only acute HF induced hyperlipidaemia. In AP, acute obese rats exhibited less pancreatic inflammation, but total histological severity between groups was not different. In the chronic experiment only obese animals succumbed before 24 h of pancreatitis, but 72‐h survival rate was not statistically different in either high‐fat experiment. Conclusion: An addition of LPS to AP decreases survival rate and intensifies the peri‐pancreatic processes. Despite significant obesity, neither hyperlipidaemia nor increased intra‐abdominal or hepatic fat influenced local pancreatic injury or survival negatively. The amount of fat per se seems not to be responsible for the deleterious influence of obesity on acute pancreatitis.

Hemoconcentration predicts local complications but not organ failure in acute pancreatitis

Hemoconcentration predicts local complications but not organ failure in acute pancreatitis

Relationship of Pancreatic and Peripancreatic Fat Necrosis to Organ Failure in Acute Pancreatitis

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Ascites of rat experimental model of severe acute pancreatitis induces lung injury.

The molecular mechanisms that lead from acute pancreatitis (AP) to multiple organ failure remain to be clarified. We previously reported that ascitic fluids from a rat model of severe acute pancreatitis (pancreatitis-associated ascitic fluids, PAAF) transcriptionally activated endothelial cells and leukocytes in vitro. To clarify the role of ascitic fluids on the development of multiple organ failure in AP, we examined the effects of PAAF on the prognosis and immunohistologic findings in cerulein pancreatitis, an experimental model of mild pancreatitis in vivo. Intraperitoneal injection of PAAF decreased the survival rates in a dose-dependent manner. Histologically, destruction of vessels, alveolar septal thickening, interstitial hypertrophy, and infiltration of inflammatory cells were prominent in the lung of PAAF-injected rats. Transcription factor, nuclear factor KB (NF-kappaB) was activated and the mRNA levels of tumor necrosis factor-alpha and interleukin-1beta were increased in the lung of the PAAF-injected rats. The permeability index assessed by Evans blue assay and the lung myeloperoxidase activity levels were significantly higher in the PAAF-injected rats than in controls. Inhibition of NF-kappaB ameliorated the histologic findings and improved the survival rates. Our results suggest that PAAF play a role in the pathogenesis of lung injury in severe AP, at least in part through the activation of NF-kappaB.

Acute Pancreatitis and Cytokines

Acute pancreatitis is accompanied by destruction and digestion of tissues, causing hypercytokinemia and hyperreactivity of leukocytes (macrophages and neutrophils) and vascular endothelial cells. As one of the biological defense mechanisms in this condition, neutrophils infiltrate vital organs such as the lung, liver, and digestive organs. When acute pancreatitis is complicated by infection, hyperreactive macrophages release a large amount of proinflammatory cytokines that activate primed neutrophils, as a "second attack." Utilizing proteolytic enzymes and oxidant, neutrophils injure the infiltrated vital organs, causing cellular damage and dysfunction of vital organs distant from the pancreas. Multiple organ failure in acute pancreatitis with septic complications can develop, at least in part, by proinflammatory cytokine release and neutrophil activation.

Which is the critical balthazar score value for indicating organ failure in acute pancreatitis?

Which is the critical balthazar score value for indicating organ failure in acute pancreatitis?

The effect of tilsuprost on the liver mitochondria in taurocholate pancreatitis in rats with antecedent acute ethanol abuse.

The damage to the liver appears to be an important aspect of multisystem organ failure in acute pancreatitis with poor prognosis. The objective of this study was to evaluate the protective effect of stable prostacyclin analogue--tilsuprost on the liver energy metabolism in taurocholate pancreatitis in rats preceded by acute ethanol intake. The respiratory control ratio (RCR) and ADP/O ratio of liver mitochondria with glutamate+malate as substrates and mitochondrial DNP (uncoupler)-dependent ATPase activity were significantly depressed after 12 h of taurocholate pancreatitis-the effects that were not significantly aggravated by antecedent acute ethanol intake. Tilsuprost (0.3 mg/kg i.g.) given just before induction of pancreatitis partly prevented the impairment of mitochondrial oxidative and phosphorylative functions, however these positive effects were limited in acute pancreatitis preceded by acute ethanol intake. These results suggest that prostacyclin analogues could be effective in the treatment of hepatic complications in acute pancreatitis, however their effectiveness could be limited in the case of acute ethanol antecedent abuse.

The use of lexipafant in the treatment of acute pancreatitis.

The pathophysiology of systemic organ failure in acute pancreatitis has been the subject of debate for many years but there is growing evidence that increase production of pro-inflammatory cytokines plays an important role. from this work and from the results of studies in experimental pancreatitis there exists a rationale for the use of PAF antagonists in the treatment of acute pancreatitis. Two pilot studies have now demonstrated a beneficial effect of the PAF antagonist Lexipafant on acute pancreatitis which may lead to an important advance in the treatment of these patients. A multicentre trial aiming to recruit 300 patients with severe acute pancreatitis is now underway in the UK, the results of which will be awaited with interest.

The Influence of Abdominal Sepsis on Acute Pancreatitis in Rats

Bacterial infection increases mortality and morbidity in acute pancreatitis. The aim of the present study was to analyze possible mechanisms by which bacterial infectious complications may worsen the course of the disease. Systemic arterial pressure, mucosal microcirculation, and intestinal, peritoneal, and pulmonary permeability of 125I-labeled human serum albumin were measured 3, 6, 12, 24, 48, and 72 h after sham operation, induction of pancreatitis (AP), abdominal sepsis (AS), or AP+AS. The mortality rate at 48 and 72 h was 33% in AS and 58 and 75%, respectively, in AP+AS, whereas there were no deaths in the AP or sham-operated groups. The systemic arterial pressure and intestinal blood flow decreased early in all study groups, with the lowest values for AP+AS. Bacterial infection aggravated the increase in intestinal, peritoneal, and pulmonary permeability to labeled albumin in pancreatitis. This was true for both intestinal endothelial permeability (blood to tissue) and mucosal barrier permeability (blood to lumen). The findings demonstrate the occurrence of circulatory failure and changes of the capillary barrier in multiple organs in acute pancreatitis. Moreover, the changes were aggravated by an intraabdominal septic challenge. The observations imply that bacterial infection may play a role in the development of multiple organ failure in acute pancreatitis, tentatively by aggravating alterations in tissue barrier function.

Induction of apoptotic cell death by pancreatitis-associated ascitic fluid in Madin-Darby canine kidney cells

We investigated the cytotoxicity on Madin-Darby canine kidney (MDCK) cells of pancreatitis-associated ascitic fluid (PAAF) collected from rats with experimental necrotizing pancreatitis. PAAF reduced viability of MDCK cells in a time- and dose-dependent manner. We detected DNA fragmentation on the PAAF-treated MDCK cells, indicating that the cytocidal action of PAAF is via apoptosis. From the results obtained, we conclude that PAAF contains factor(s) inducing apoptosis on MDCK cells, and we assume that apoptotic cell death is involved in the mechanism of organ failure in acute pancreatitis.