Systemic Complications Of Acute Pancreatitis Research Articles

Mo1354 Age Adjusted Charlson Comorbidity Index: A Prognostic Tool to Measure Disease Burden: Can We Use It in Acute Pancreatitis? A Retrospective Observational Study in Minority Populations

Background: Age Adjusted Charlson Comorbidity Index (AACCI) has been studied in the past to predict morbidity and mortality in various clinical conditions. At the same time there has been various markers and scores developed to predict morbidity and mortality in acute pancreatitis. Most of the tools used in acute pancreatitis, were unable to reach adequate sensitivity and specificity. However AACCI was never studied in the setting of acute pancreatitis. We hypothesized that AACCI which reflects the influence of burden of comorbid conditions, may predict outcomes in acute pancreatitis. We studied correlation between AACCI and length of hospital stay in individuals admitted with acute pancreatitis.Methods: We conducted retrospective observational study between January 1, 2009 and June 30, 2011 including all individuals admitted to our institutionwith acute pancreatitis.We collected demographic, laboratory, and radiological data. We used Length of Stay (LOS) as a measure of inpatient morbidity and extracted LOS days from medical records. We calculated AACCI based on comorbid conditions noted in electronic medical records. We divided study population into 3 groups based on AACCI score, Group A (scores 0 to 2), Group B (scores 3 to 5) and Group C (score 6 and above). We analyzed data using standard statistical methods and JMP11 software. Results: There were 209 individuals who met the inclusion criteria as per current definition of acute pancreatitis. Men and women were represented equally. There were 51% Hispanics and 49% non-Hispanics of which 80% were African Americans. There were no significant differences in LOS between women and men (10.25 vs. 10.42 days, p 0.91), between Hispanics and non-Hispanics (9.23 vs. 10.82, p 0.28). Also we did not notice any difference in length of stay based on etiology of acute pancreatitis. However we found significant increase in length of stay parallel to increase in AACCI (Table 1). (Group A 8.31, Group B 11.09 and Group C 15.44 days, p 0.002) Conclusion: Increase in Age Adjusted Charlson Comorbidity Index predicted prolonged Length of Stay, in patients hospitalized with acute pancreatitis. Our study is unique in studying relation between AACCI and LOS in acute pancreatitis especially in minority populations. Further studies are needed to relate AACCI with various local and systemic complications in acute pancreatitis, which may give single tool to predict outcomes without elaborative laboratory or radiological work up. Table 1

Effect of lornoxicam therapy on expression of TLR2 and TLR4 mRNA during systemic complications of acute pancreatitis.

Primary pancreatic injury that occurs in acute pancreatitis leads to necrosis of pancreatic cells and is accompanied by the development systemic inflammatory response of varying severity. Systemic inflammatory response, in turn, can lead to the development of multiple organ dysfunction syndrome and death of patients. The release of damage-associated molecular patterns into the extracellular space is the trigger pathological mechanism underlying these processes. The released patterns exert their effects via Toll-like receptors (TLR). These findings suggest that TLR can be considered a new target for therapeutic intervention in acute pancreatitis. We studied mRNA expression of TLR2 and TLR4 in the peripheral blood mononuclear cells from the patients with acute pancreatitis and showed a decrease in the examined parameters associated with lornoxicam treatment. Anti-mediator therapy decreased mortality in these patients.

Acute Lipotoxicity Regulates Severity of Biliary Acute Pancreatitis without Affecting Its Initiation

Obese patients have worse outcomes during acute pancreatitis (AP). Previous animal models of AP have found worse outcomes in obese rodents who may have a baseline proinflammatory state. Our aim was to study the role of acute lipolytic generation of fatty acids on local severity and systemic complications of AP. Human postpancreatitis necrotic collections were analyzed for unsaturated fatty acids (UFAs) and saturated fatty acids. A model of biliary AP was designed to replicate the human variables by intraductal injection of the triglyceride glyceryl trilinoleate alone or with the chemically distinct lipase inhibitors orlistat or cetilistat. Parameters of AP etiology and outcomes of local and systemic severity were measured. Patients with postpancreatitis necrotic collections were obese, and 13 of 15 had biliary AP. Postpancreatitis necrotic collections were enriched in UFAs. Intraductal glyceryl trilinoleate with or without the lipase inhibitors resulted in oil red O-positive areas, resembling intrapancreatic fat. Both lipase inhibitors reduced the glyceryl trilinoleate-induced increase in serum lipase, UFAs, pancreatic necrosis, serum inflammatory markers, systemic injury, and mortality but not serum alanine aminotransferase, bilirubin, or amylase. We conclude that UFAs are enriched in human necrotic collections and acute UFA generation via lipolysis worsens pancreatic necrosis, systemic inflammation, and injury associated with severe AP. Inhibition of lipolysis reduces UFA generation and improves these outcomes of AP without interfering with its induction.

Inferior Vena Cava Thrombosis in Acute Pancreatitis: A Rare Vascular Complication

Introduction: The systemic complications of acute pancreatitis are myriad and are mostly a consequence of systemic inflammatory response. Isolated portal and superior mesenteric vein thrombosis are well recognized complications of acute pancreatitis, while thrombosis involving the inferior vena cava (IVC) is extremely rare. Case Report: A 79-year-old male with history of chronic alcoholism presented with upper abdominal pain of 3 weeks' duration. Initial evaluation revealed epigastric tenderness and a serum lipase level of 1,041 U/L. Abdominal computerized tomography showed inflammatory stranding in the pancreatic head, 7-mm pancreatic duct calculus, and punctate calcifications in the pancreatic body suggestive of acute on chronic pancreatitis. He also had a pancreatic pseudocyst and 3.4-cm thrombosis in the IVC above the level of right renal vein with 60% luminal obstruction. He was started on intravenous heparin. He developed abdominal distension and a fall in the hematocrit in the next 2 days. Repeat imaging revealed hemorrhage into the pseudocyst with probable rupture into the peritoneal cavity. Anticoagulation was stopped and he was conservatively managed with blood transfusion. An IVC filter was placed. The workup for hypercoagulabe state including factor V Leiden mutation, prothrombin gene mutation, and activity of protein C, protein S, and antithrombin III was unremarkable. An ERCP done later showed pancreatic duct stricture with calculus that was not amenable to endoscopic treatment. He is on followup and is doing symptomatically well. Discussion: Venous thrombosis occurring outside the splanchnic circulation is very rarely described in pancreatitis. Release of pancreatic proteolytic enzymes due to acute inflammation is the most likely mechanism responsible for thrombosis of the splenic, portal, and superior mesenteric veins. IVC thrombosis can result from systemic inflammatory response with hypercoagulable state or a pancreatic cyst that compresses or penetrates the IVC. Pulmonary thromboembolism is a potential cause of mortality and morbidity in patients with IVC thrombosis, hence early recognition of this complication is vital. There are isolated reports of patients with acute pancreatitis and extra-splanchnic venous thrombosis who have been successfully treated with anticoagulation. In the setting of a pancreatic pseudocyst, anticoagulation is fraught with danger as it can result in hemorrhage into the cyst as described in our case. IVC filter placement is a good alternative in patients who cannot undergo anticoagulation or develop bleeding after anticoagulation. Literature regarding the optimal strategy and the duration of anticoagulation in these patients is minimal.

Mean platelet volume (MPV) as prognostic factor in acute pancreatitis (AP)

Introduction: Mean platelet volume (MPV) is a machine-calculated measurement of the average size of platelets and is typically included in blood tests as part of the complete blood count. Vascular thrombosis and systemic hypercoagulable states are well documented complications of acute pancreatitis (AP). Higher values of MPV have been associated with thrombotic disorders. According to the literature, only few studies have investigated the association between AP and MPV. Objectives: To determine whether the value of MPV at admission correlates with the occurrence of local and systemic complications of AP ; lethal outcomes ; and severe form of AP, according to modified Atlanta criteria. Patients and methods: 53 patients (35 male and 18 female) were enrolled in this retrospective study. MPV values were obtained on an automated hematology analyzer (Olympus AU 640, Tokio, Japan). Student’s t-test was used for statistical analysis. Results: There were no statistically significant differences in the average values of MPV regarding local complications (7.51±0.99 vs. 7.91±1.24, p=0.22), systemic complications (7.60±1.05 vs. 7.72±1.22, p=0.76), severe form of AP (7.47±0.97 vs. 7.94±1.22, p=0.13) or lethal outcomes (7.58±1.03 vs. 7.97±1.38, p=0.41). Conclusion: Our study did not confirm the value of MPV in predicting complications in the course of AP.

Acute pancreatitis in obese patients

Introduction: Obesity increases severity of acute pancreatitis by unclear mechanisms. Recent clinical studies demonstrate that all major complications are more common and more severe in patients who are obese. Patients with higher body mass index have increased risk of local and systemic complications of acute pancreatitis and patients with android fat distribution and higher waist circumference are at greater risk for developing the severe acute pancreatitis (SAP). Aims:We investigated the relationship between visceral adipose tissue and acute pancreatitis. Patients &methods:We examined 13 patients with acute pancreatitis. In 6 patients BMI was more 30. Computed tomography was performed in all patients. Results: Pancreatitis induces the activation of peritoneal macrophages and a strong inflammatory response in mesenteric sites of adipose tissue. In obese humans, we found that an increase in the volume of intrapancreatic adipocytes was associated with more extensive pancreatic necrosis during acute pancreatitis and that acute pancreatitis was associated with multisystem organ failure in obese individuals. Patients with SAP had higher BMIs and more intrapancreatic fat than those with mild AP. Conclusion: The results confirm the involvement of adipose tissue on the progression of systemic inflammatory response during acute pancreatitis. However, there is a considerable diversity in different adipose tissue sites. These differences need to be taken into account in order to understand the progression from local pancreatic damage to systemic inflammation during acute pancreatitis. Therapeutic approaches that target unsaturated fatty acid-mediated lipotoxicity may reduce adverse outcomes in obese patients with critical illnesses such as severe acute pancreatitis.

The Role of IL-6, 8, and 10, sTNFr, CRP, and Pancreatic Elastase in the Prediction of Systemic Complications in Patients with Acute Pancreatitis

Background and Aim. Early assessment of severity in acute pancreatitis (AP) is a key measure to provide rational and effective management. The aim of our study is to determine the prognostic value of interleukins (IL) 6, 8, and 10, soluble receptor for tumor necrosis factor (sTNFr), pancreatic elastase (E1), and C-reactive protein (CRP) as predictors of systemic complications in AP. Patients and Methods. A hundred and fifty patients with confirmed AP were enrolled in the study. The severity of AP was defined according to Atlanta criteria. Measurements of interleukins and sTNFr were performed on the first day of admission. CRP and E1 levels were assessed on admission and after 48 hours. ROC analysis was performed for all parameters. Results. Interleukins and sTNFr significantly differentiated patients with systemic complications from those without. Elevation of IL-6 showed the highest significance as a predictor (P = 0.001). CRP and elastase levels did not differ between mild and severe cases on admission, but reached statistical significance when measured on the third day (P = 0.002 and P = 0.001, resp.). Conclusion. Our study confirmed that IL-6, IL-8, IL-10, and sTNFr measured on admission, and CRP and pancreatic elastase measured on third day of admission represent valuable prognostic factors of severity and systemic complications of AP.

T1306 Multiplex Serum Marker Panel Accurately Predicts Systemic Complications of Acute Pancreatitis

T1306 Multiplex Serum Marker Panel Accurately Predicts Systemic Complications of Acute Pancreatitis

M1827 NF-κB Activation in Myeloid Cells Contributes to Local and Systemic Complications in Acute Pancreatitis

M1827 NF-κB Activation in Myeloid Cells Contributes to Local and Systemic Complications in Acute Pancreatitis

Taurocholate-Induced Pancreatitis

The outcome from acute pancreatitis depends on the severity of systemic complications. To be able to investigate mechanisms underlying the development of these systemic complications in acute pancreatitis in both wild-type and genetically engineered animal models, a mouse model of severe necrotizing pancreatitis was developed and characterized. Pancreatitis was induced by retrograde infusion of sodium taurocholate into the common bile duct in mice. After determining the optimum volume and concentration of taurocholate, the pancreatic damage and systemic inflammatory response were compared with those in cerulein-induced pancreatitis. Pancreatic damage was higher in taurocholate pancreatitis than hyperstimulation-induced pancreatitis (24 hours: cerulein, 5.8 +/- 0.2 points; taurocholate, 14.8 +/- 0.8 points; P < 0.001) and mortality reached up to 60% within the first 24 hours after taurocholate administration. Pulmonary damage was detected, as measured by an increase in albumin in bronchoalveolar lavage fluid only in taurocholate-induced pancreatitis (12 hours: cerulein, 97.1 +/- 22.83 mg/g of protein; taurocholate, 234.0 +/- 32.7 mg/g of protein; P < 0.001). Furthermore, plasma interleukin 6 concentration was significantly elevated in mice with taurocholate-induced pancreatitis (12 hours: cerulein, 2.6 +/- 6.1 pg/mL; taurocholate, 2168.8 +/- 941.7 microg/mL; P < 0.001) as compared with all other groups. Taurocholate pancreatitis is a reliable model for severe necrotizing pancreatitis in mice with significantly greater pancreatic damage and systemic inflammatory response in comparison with cerulein-induced pancreatitis.

Obesity Correlates With Early Hyperglycemia in Patients With Acute Pancreatitis Who Developed Organ Failure

Early hyperglycemia in acute pancreatitis (AP) is a prognostic sign of severe attack. Obesity, another risk factor for severe AP, is associated with impaired glucose regulation. We hypothesized that obesity is related to early hyperglycemia in patients with severe AP. Forty-four patients with severe AP with organ failure and 127 control patients with AP (33 severe AP and 94 mild AP) but without organ failure were studied. Plasma glucose and patients' height and weight for calculation of body mass index (BMI) were measured at admission. Body mass index was higher in organ failure patients than in controls (median, 27.0 kg/m2 [interquartile range, 24.9-30.4 kg/m2] vs 25.2 kg/m2 [interquartile range, 23.3-27.9 kg/m2; P = 0.007). Glucose level correlated with BMI in organ failure patients (r = 0.463, P = 0.002) but not in controls (r = 0.096, P = 0.28). Eight (18%) organ failure patients and 7 (5.5%) controls had prior type 2 diabetes (P = 0.025). In a logistic regression model, admission glucose level was the only independent predictor of organ failure. Obesity may contribute to early hyperglycemia in patients with AP. Multivariate analysis indicated that obesity is not an independent risk factor for organ failure, but it correlates with early hyperglycemia, which may predispose to systemic complications in AP.

Interleukin-18: a pro-inflammatory cytokine that plays an important role in acute pancreatitis

A large body of clinical and experimental evidence suggests that cytokines play a key role in the pathogenesis of local and systemic complications of acute pancreatitis. IL-18 is a pro-inflammatory cytokine that plays a key role in many human diseases, including acute pancreatitis. This review focuses on the present understanding in IL-18 and its potential role in acute pancreatitis. IL-18 levels reflect the severity of acute pancreatitis and display a significant negative correlation with the concentrations of antioxidative damage factors, serum selenium and glutathione peroxidases (GPx). The relationship between IL-18 and other pro-inflammatory cytokines shows that IL-18 is one of the key mediators of inflammation in the pathogenesis of acute pancreatitis. Elevation of serum IL-18 levels may mediate acute pancreatitis associated liver injury. The use of IL-18 antagonists as direct routes to block IL-18 activity and P2X7 receptor antagonists and interleukin-1β-converting enzyme (ICE) inhibitors as indirect routes to block IL-18 activity suggest that specific therapeutic inhibition of IL-18 is a promising therapeutic approach for acute pancreatitis.

The Role of Nonenhanced Magnetic Resonance Imaging in the Early Assessment of Acute Pancreatitis

Computed tomography (CT), especially contrast-enhanced CT (CECT), provides important information on the severity and prognosis of acute pancreatitis (AP). Magnetic resonance imaging (MRI) has become a useful tool as an alternative to CT in the assessment of AP. The primary aim of our study was to determine the diagnostic value of nonenhanced MRI (NEMRI) to assess severity and predict outcome in patients with AP from the third to fifth day after admission. We also correlated MRI findings with CT and biochemical parameters. The study included 101 patients (49 men, 52 women, median age 62 yr, range 20-82) with a diagnosis of AP admitted to our hospital between January 1, 2004 and June 31, 2005. The inclusion criteria consisted of a combination of clinical features, a typical case history, elevation of serum pancreatic enzymes, and diagnosis confirmed by imaging studies. Contrast-enhanced spiral CT exams were performed in all patients from the third to fifth day after admission, and Balthazar grade and CT severity index were calculated. All patients underwent NEMRI, and MR severity index (MRSI) was calculated. We also performed magnetic resonance cholangiopancreatography (MRCP) in all patients to detect bile duct lithiasis. Significant correlation between CECT and NEMRI was found for Balthazar grade (P<0.001) and the assessment of pancreatic necrosis (P<0.001), as well as between the combined severity indices (rho=0.819, P<0.001). MRSI correlated with Ranson score (rho=0.656, P<0.01), C-reactive protein (CRP) levels 48 h after admission (rho=0.502, P<0.01), appearance of systemic complications (rho=0.576, P<0.01), and length of hospital stay (rho=0.484, P<0.01). Considering the Atlanta criteria as the gold standard and the Ranson score, no difference in sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the two methods was observed. Comparing the group of patients with presumed acute pancreatic hemorrhage with the group of patients with severe AP, we found a significantly higher APACHE II score on the first day (P<0.05), that the development of systemic complications was more frequent (P < 0.05), and that the hospital stay and ICU management of patients with MRI signs of pancreatic hemorrhage tended to be longer. NEMRI is comparable to CECT in the early assessment of the severity of AP, and both methods are equally efficient in predicting local and systemic complications of AP. MRI has a potential advantage over CT in detecting bile duct lithiasis and pancreatic hemorrhage.

Effect of a selective thromboxane A2 synthetase inhibitor on the systemic changes induced by circulating pancreatic phospholipase A2

In acute pancreatitis, pancreatic phospholipase A(2) (PLA2) in the circulating blood hydrolyzes phospholipids contained in plasma lipoproteins, liberating eicosanoid precursors that are subsequently converted to various eicosanoids. The pathophysiological significance of eicosanoid synthesis via this pathway is unknown. The aim of this study was to clarify the role of thromboxane A(2) (TXA(2)) synthesis by circulating pancreatic PLA(2) in the pathogenesis of the systemic complications of acute pancreatitis. Guinea pigs were divided into two groups: a control group and an ozagrel group, which received intravenous administration of ozagrel, a selective TXA(2) synthetase inhibitor. Pancreatic PLA(2) was infused intravenously in both groups for 30 min, and systemic changes during the infusion were examined. In the control group, there was an increase in plasma thromboxane B(2) (TXB(2)) concentration, a decrease in mean arterial pressure and heart rate, a decrease in arterial base excess (BE), bicarbonate concentration (HCO(3) (-)), and pH, a decrease in platelet count and plasma fibrinogen concentration, and a shortened prothrombin time during the infusion of pancreatic PLA(2). In the ozagrel-treated group, changes in plasma TXB(2) concentration, BE, HCO(3) (-), and platelet count were significantly inhibited. TXA(2) synthesis by circulating pancreatic PLA(2) contributes to metabolic acidosis and thrombocytopenia during acute pancreatitis.

Obesity Is a Definitive Risk Factor of Severity and Mortality in Acute Pancreatitis: An Updated Meta-Analysis

Background/Aims: Obesity is considered a risk factor in patients with acute pancreatitis. However, the relationship between obesity and mortality in this disease has not been confirmed definitively even in a previous meta-analysis. Since the publication of our previous meta-analysis, one study has been reported about the prognostic value of obesity in acute pancreatitis. We have performed a new meta-analysis to confirm the relationship between obesity and the outcome of acute pancreatitis. Data Sources: A MEDLINE search using ‘pancreatitis’, ‘obesity’ and ‘body mass index’ as search terms. Review Methods: Clinical studies which investigated the prognostic value of obesity in acute pancreatitis with the following criteria: (a) inclusion of mild and severe acute pancreatitis; (b) use of body mass index (BMI) as the measure of obesity; (c) definition of obesity as BMI ≧30 kg/m²; (d) definition of severity of acute pancreatitis according to the criteria established in the Atlanta Symposium. Five studies including patients with mild and severe acute pancreatitis and obesity measured by BMI were analyzed. The end points of the meta-analysis were the severity of acute pancreatitis, local complications, systemic complications and mortality. Pooled odds ratio (OR) and confidence intervals (CI) were calculated according to the Mantel-Haenszel method, and heterogeneity was assessed by the multiplicative inverse variance method. Results: Seven hundred and thirty-nine patients were included. There was no heterogeneity for the variables severity, systemic complications, local complications and mortality among the included studies. Severe acute pancreatitis was significantly more frequent in obese patients (OR 2.9, 95% CI 1.8–4.6). Furthermore, those patients developed significantly more systemic (OR 2.3, 95% CI 1.4–3.8) and especially local complications (OR 3.8, 95% CI 2.4–6.6). In this new analysis, mortality was also higher in obese patients (OR 2.1, 95% CI 1.0–4.8). Conclusion: Obesity is not only a risk factor for the development of local and systemic complications in acute pancreatitis: it also increases the mortality of this disease.

Protease-activated receptor 2 exerts local protection and mediates some systemic complications in acute pancreatitis

Background & Aims: Protease-activated receptor 2 can be stimulated by interstitially released trypsin during acute inflammation of the pancreas. In this study, we investigated the roles of pancreatic and circulatory protease-activated receptor 2 in the pathogenesis of acute pancreatitis by using in vitro and in vivo model systems. Methods: Physiological and pathologic effects of protease-activated receptor 2 activation were measured in isolated pancreatic cells and in rats with experimental pancreatitis. Consequences of protease-activated receptor 2 activation on the systemic and inflammatory responses were measured after treatments with trypsin or protease-activated receptor 2-activating peptide. Results: Stimulation of protease-activated receptor 2 in rat pancreatic acinar cells activated short-lasting (Ca 2+ signaling) and long-lasting (extracellular signal-related kinase) signaling pathways and protected the cells against bile-induced cell damage. More importantly, protease-activated receptor 2 activation ameliorated the pathologic effects observed in the in vivo model of cerulein-induced pancreatitis. Trypsin in the circulation of rats with taurocholate-induced severe acute pancreatitis reached levels sufficient to activate endothelial and immune cells to stimulate nitric oxide and interleukin-8 production, respectively. Most notably, activation of systemic protease-activated receptor 2 by circulating protease-activated receptor 2 agonists induced a hemodynamic response pattern similar to that observed in rats with severe acute pancreatitis. The effects of protease-activated receptor 2 agonists and acute pancreatitis were not additive. Conclusions: These findings suggest that protease-activated receptor 2 may have a dual role in acute pancreatitis: protecting acinar and duct cells against pancreatitis-induced cell damage while mediating or aggravating the systemic complications of acute pancreatitis, which are the major cause of mortality in the early phase of necrotizing pancreatitis.

Treatment with Met-RANTES reduces lung injury in caerulein-induced pancreatitis

Severe acute pancreatitis leads to a systemic inflammatory response characterized by widespread leucocyte activation and, as a consequence, distant lung injury. In CC chemokines the first two cysteine residues are adjacent to each other. The aim of this study was to evaluate the effect of Met-RANTES, a CC chemokine receptor antagonist, on pancreatic inflammation and lung injury in caerulein-induced acute pancreatitis in mice. Acute pancreatitis was induced in mice by hourly intraperitoneal injection of caerulein. Met-RANTES was administered either 30 min before or 1 h after starting caerulein injections, and pancreatic inflammation and lung injury were assessed. There were five groups of eight mice each including controls. Treatment with Met-RANTES had little effect on caerulein-induced pancreatic damage. Met-RANTES, however, reduced lung injury when given either before administration of caerulein (mean(s.e.m.) lung myeloperoxidase (MPO) 1.47(0.19) versus 3.70(0.86)-fold increase over control, P = 0.024; mean(s.e.m.) microvascular permeability 1.15(0.05) versus 3.57(0.63) lavage to plasma fluorescein isothiocyanate-labelled albumin fluorescence ratio (L/P) per cent, P = 0.002) or after caerulein administration (lung MPO 1.96(0.27) versus 3.65(0.63)-fold increase over control, P = 0.029; microvascular permeability 0.94(0.04) versus 2.85(0.34) L/P per cent, P < 0.001). Treatment with Met-RANTES reduces lung damage associated with caerulein-induced pancreatitis in mice. Chemokine receptor antagonists may be of use for the treatment of the systemic complications of acute pancreatitis.

In vivo effect of pancreatic phospholipase A2 on the arachidonic acid cascade.

In acute pancreatitis, pancreatic phospholipase A2 increases in systemic circulation. Yet the pathophysiological significance is controversial, because previous in vitro studies have shown that the enzyme has little cytotoxicity or ability to activate the arachidonic acid cascade by itself in contrast to other isozymes. The aims of this study are to examine the effect of pancreatic phospholipase A2 on the arachidonic acid cascade in vivo; to explain the discrepancy, if present, between in vitro and in vivo findings; and to reassess the pathophysiological significance of circulating pancreatic phospholipase A2. Pancreatic phospholipase A2 was infused intravenously in guinea pigs, and changes in the arachidonic acid cascade, plasma lipoprotein, and cardiopulmonary function were investigated. Plasma concentrations of 6-keto-prostaglandin F1alpha, prostaglandin E2, and thromboxane B2 increased after intravenous (iv) infusion of pancreatic phospholipase A2. Some of the plasma phospholipids such as phosphatidylcholine and phosphatidylethanolamine decreased, and free dihomo-gamma-linolenic acid, arachidonic acid, and eicosapentaenoic acid were detected in plasma. These changes were accompanied with decreases in blood pressure, heart rate, and base excess. Circulating pancreatic phospholipase A2 activates the arachidonic acid cascade, probably by supplying free eicosanoid precursors from plasma lipoprotein to eicosanoid-producing cells. It is supposed to be a cause of systemic complications in acute pancreatitis.

Inflammatory mediators in human acute pancreatitis: clinical and pathophysiological implications

BACKGROUNDThe time course and relationship between circulating and local cytokine concentrations, pancreatic inflammation, and organ dysfunction in acute pancreatitis are largely unknown.PATIENTS AND METHODSIn a prospective clinical study, we measured...

Potential role of interleukin-18 (IL-18) in the development of local and systemic complications in acute pancreatitis

Potential role of interleukin-18 (IL-18) in the development of local and systemic complications in acute pancreatitis