Five percent of alcoholics develop an acute pancreatitis (AP). The mechanism leading to pancreatic injury is not yet understood. Microcirculatory disorders seem to play a pivotal role. The objective of this study was to compare alcoholic pancreatic injury in response to intravenous and intragastric routes of alcohol administration.

Alcohol was applied in rats intravenously (IV) or gastric via a surgical implanted feeding tube (IG). Serum alcohol concentration was maintained between 1.5‰ and 2.5‰. Four subgroups (n = 6/group) were examined in the IV/IG arm and compared with healthy controls. Pancreatic microcirculation, enzyme levels, and morphological damage were assessed after 3, 6, 12, and 24 hours.

Microcirculatory analysis showed significantly disturbed pancreatic perfusion and increased adherent leukocytes in IV and IG animals. In IV and IG groups, serum amylase was increased without morphological signs of AP compared with healthy controls.

Alcohol application does not induce AP in rodents, but impairs pancreatic microcirculation irrespectively of the application route. Intravenous application is commonly used and shows no disadvantages compared with the physiological intragastric application form. Therefore, the intravenous route offers a valid model, which mimics the physiological process for further studies of the influence of acute alcohol intoxication on the pancreas.

Aim of the study was to investigate pancreatic microcirculatory and histopathological changes in rats after chronic ethanol liquid diet feeding.

To investigate the influence of chronic alcohol exposition (CAE) on the pancreas, rats were fed with either Lieber-DeCarli (LDC) control diet or LDC alcohol diet for 2, 4, or 6 weeks and received additionally an acute ethanol administration (AEA) for 90 minutes. Intravital microscopy was performed at baseline, 45 minutes, and 90 minutes after starting AEA. Pancreatic perfusion and leukocyte adhesion were assessed, and pancreatic damage was evaluated by histology.

Capillary perfusion was reduced in all animals after AEA. After previous CAE, there was a significant increase in leukocyte adhesion compared to control groups (P < 0.05). Most importantly, leukocyte adhesions were already increased at baseline after CAE and before the acute bolus was infused (P < 0.05). Moreover, only animals that received LDC alcohol diet developed mild histological changes consisting of pancreatic edema and vacuoles, whereas those that received AEA alone did not. Histological changes and cytokine levels correlated with the duration of prior CAE.

Long-term alcohol intake activates endothelium and sensitizes the pancreas for inflammatory reactions leading to an increased likelihood of a clinically evident episode of acute pancreatitis.

Acute pancreatitis is an inflammatory disease that is mild and self-limiting in about 80% of cases. However, severe necrotizing disease still has a mortality of up to 30%. Differentiated multimodal treatment concepts are needed for these patients, including a multidisciplinary team (intensivists, gastroenterologists, interventional radiologists, and surgeons). The primary therapy is supportive. Patients with infected pancreatic necrosis who are septic undergo interventional or surgical treatment, ideally not before the fourth week after onset of symptoms. This article reviews the pathophysiologic mechanisms of acute pancreatitis and describes clinical pathways for diagnosis and management based on the current literature and guidelines.

The mechanism of alcoholic pancreatitis is still unknown. It is of special interest why only about 5% of all alcoholics develop an episode of pancreatitis. We evaluated the role of long-term alcohol intake in the pathogenesis of alcoholic pancreatitis in rats.

To evaluate the effect of long-term alcohol intake, rats were fed either a Lieber-DeCarli control diet (CD) or a Lieber-DeCarli alcohol diet (AD) for 6 weeks. Then, rats were infused over 2 h with either Ringer's solution (CO) or ethanol (E). In additional animals, alcoholic pancreatitis was induced by ethanol combined with hyperlipidemia and temporary pancreatic duct obstruction (EFO). Controls received Ringer's solution combined with hyperlipidemia and temporary pancreatic duct obstruction (RFO). Intravital microscopy (pancreatic perfusion and leukocyte adhesion), alcohol concentrations, amylase, lipase, cholesterine and triglyceride levels in plasma, myeloperoxidase activity and histology were evaluated at different time intervals.

In those animals which received the Lieber-DeCarli control diet, capillary perfusion was reduced in the E group and further reduced in the EFO group as compared to the controls (CO, RFO; p < 0.01). Leukocyte adhesion was significantly increased in rats receiving E (p < 0.01), and was further increased in the combination group EFO (p < 0.01). EFO induced histologically evident acute pancreatitis. The additional administration of a long-term alcohol diet further increased microcirculatory disturbances and pancreatic injury significantly (EFO-AD > EFO-CD).

This study shows that alcoholic pancreatitis is induced by the combination of ethanol and individual cofactors. Chronic alcohol abuse intensifies these changes. Therefore, long-term alcohol intake seems to be a major factor in the pathogenesis of alcoholic pancreatitis.

Systemic complications including pancreatitis-associated lung injury (PALI) are critical factors that determine the outcome of severe necrotizing pancreatitis (SNP). The aim of the present study was to evaluate the role of chronic alcohol exposure on the development of PALI.

48 rats were fed either a Lieber deCarli control or alcohol diet for 6 weeks. After completion, SNP was induced by intraductal infusion of bile salt followed by intravenous infusion of cerulein over 6 h. Control animals received i.v. Ringer's solution. Intravital microscopy of the liver was performed 6 h after induction of SNP to evaluate hepatic perfusion and leukocyte adhesion. Serum parameters, edema, inflammation, and histological changes were evaluated at 12 h. IL-6 levels were evaluated in portal venous and systemic blood as well as in pancreatic tissue homogenates.

Alcohol pretreatment did not affect pancreatic injury in SNP. PALI was aggravated after alcohol ingestion. These animals showed increased hepatic microcirculatory disturbances, compared to SNP alone. IL-6 showed peak levels in SNP with alcohol pretreatment, although they were also elevated in SNP alone. Systemic levels of IL-6 were higher than in the portal vein.

In SNP, alcoholic pretreatment increases pulmonary damage, while pancreatic injury is identical. The liver seems to participate in this effect by increased hepatic cytokine release.

Use of alcohol is a worldwide habit regardless of socio-economic background. Heavy alcohol consumption is a potential risk factor for induction of pancreatitis. The current review cites the updated literature on the alcohol metabolism, its effects on gastrointestinal and pancreatic function and in causing pancreatic injury, genetic predisposition of alcohol induced pancreatitis. Reports describing prospective mechanisms of action of alcohol activating the signal transduction pathways, induction of oxidative stress parameters through the development of animal models are being presented.

Alcohol induces pancreatic ischemia, but the mechanisms promoting pancreatic inflammation are unclear. We investigated whether cigarette smoke inhalation is a cofactor in the development of ethanol-induced pancreatic injury. Cigarette smoke was administered to anesthetized rats alone or in combination with intravenous ethanol infusion. Control animals received either saline or ethanol alone. Pancreatic capillary blood flow and leukocyte-endothelium interaction in postcapillary venules were evaluated by intravital microscopy. Leukocyte sequestration was assessed by measurement of myeloperoxidase activity in pancreatic tissue, and pancreatic injury evaluated by histology. Ethanol decreased pancreatic blood flow progressively over 90 minutes (p < 0.001 vs. baseline), but neither leukocyte-endothelium interaction nor leukocyte sequestration was altered. Cigarette smoke alone reduced pancreatic blood flow temporarily (p < 0.01 vs. baseline) and increased leukocyte-endothelium interaction (roller p < 0.001, sticker p < 0.01 vs. baseline). Cigarette smoke potentiated the impairment of pancreatic capillary perfusion caused by ethanol, and both the number of rolling leukocytes and myeloperoxidase activity levels were increased compared to ethanol or nicotine administration alone (p < or = 0.05 and p < or = 0.01, respectively). This study demonstrates that ethanol induces pancreatic ischemia and that cigarette smoke leads to both temporary pancreatic ischemia and minimal leukocyte sequestration. Cigarette smoke potentiates the amount of pancreatic injury generated by ethanol alone. Smoking therefore seems to be a contributing factor in the development of alcohol-induced pancreatitis in the rat model.

The ingestion of one or two alcoholic drinks can affect heart rate, blood pressure, cardiac output, myocardial contractility, and regional blood flow. These actions generally are not clinically important. In the presence of cardiovascular disease, however, even such small quantities of alcohol might result in transient unfavorable hemodynamic changes. Moreover, alcohol abuse can produce cardiac arrhythmias, hypertension, cardiomyopathy, stroke, and even sudden death. In contrast, moderate alcohol use produces changes that have an overall favorable effect on atherosclerotic-related vascular diseases. Because cardiovascular disease due to atherosclerosis is the leading cause of death in Western society, this desirable effect of alcohol use outweighs its detrimental actions, resulting in favorable findings in population studies. Nevertheless, the body of evidence argues against encouraging alcohol use for its cardiovascular effects.

The objective of this study was to investigate the effects of ethanol on pancreatic blood flow and interstitial pH in chronic pancreatitis.

Ethanol is known to contribute to the development of both acute and chronic pancreatitis. However, it is unclear how ethanol precipitates episodes of acute pancreatic inflammation in the setting of chronic pancreatitis. In a model of chronic pancreatitis in cats, it is known that pancreatic blood flow is abnormally low and decreases further after ethanol ingestion. Because it is possible that this reduction in blood flow might be damaging to the pancreas, we investigated the effects of ethanol on pancreatic interstitial pH, an index of pancreatic ischemia.

In normal cats and cats with obstructive chronic pancreatitis, pancreatic blood flow and interstitial pH were measured using the hydrogen gas clearance technique and pH microelectrode, respectively.

In normal cats, intragastric, but not intravenous, ethanol reduced both pancreatic blood flow by 62% (p < 0.05) and interstitial pH (7.38 +/- 0.03 to 7.20 +/- 0.03, p < 0.05). In cats with chronic pancreatitis in which basal pancreatic blood flow was already only 60% of normal flow, both intragastric and intravenous ethanol decreased both pancreatic blood flow (intragastric, 40% decrease, p < 0.05; intravenous, 34% decrease, p < 0.05) and interstitial pH (intragastric, 7.24 +/- 0.04 to 7.08 +/- 0.04, p < 0.05; intravenous 7.20 +/- 0.08 to 7.07 +/- 0.07, p < 0.05).

This profound decrease in pH, lasting up to 2 hours after ethanol exposure in the chronic pancreatitis animals, suggests the possibility of ischemic cellular damage to the pancreas. These findings may explain the pathogenesis of bouts of acute pancreatic inflammation after ethanol ingestion in the setting of chronic disease.

The effects of intravenous ethanol and ethanol plus furosemide on pancreatic capillary blood flow (PCBF) were investigated using a laser-Doppler flowmeter. Forty Sprague-Dawley male rats were divided into 4 groups: (1) control, (2) 80% ethanol, (3) 80% ethanol plus furosemide, and (4) furosemide. Mean arterial blood pressure and heart rate were monitored. Levels of serum amylase, calcium, electrolytes, ethanol, and furosemide (groups 3 and 4) were measured, and samples of pancreatic tissue were obtained. The ethanol and furosemide levels were statistically different (p < 0.05). PCBF significantly decreased (p < 0.05) in group 2, increased (p < 0.05) in group 3, and did not differ (p > 0.05) between groups 1 and 4. Histopathologic analysis revealed swollen acini in group 2 and sparse focal necrosis without acinar swelling in group 3. The depressant effect of ethanol on PCBF may be the result of its direct action on pancreatic cells causing edema and capillary compression rather than on primary vascular control mechanisms that adjust blood flow. Furosemide counters this effect.

Three cases of chronic alcoholic pancreatitis associated with aberrant pancreas are reported. All three patients underwent laparotomy, and an aberrant pancreas was found in the jejunum of each of the three patients. Microscopic examination of the aberrant pancreas did not show any changes suggestive of chronic pancreatitis, despite severe chronic pancreatitis in the main pancreas.

The present study was done to determine the influence of single oral, intravenous and intraperitoneal ethanol administration at pre-existing pancreatic juice edema on frequency and severity of acute pancreatitis (AP). The rats were divided into six control (isolated treatment) and five study groups (edema plus varied ethanol application). 24 h postoperatively quality and quantity of macroscopic and histopathologic changes were graded on an arbitrary scale. While in the controls AP was not induced in any rat, in the study groups extrapancreatic fat necrosis and histologic lesions of the pancreas were found in the majority of animals. The individual rats revealed a remarkable variation of the severity of changes. A detailed differentiation of pancreatic necroses revealed a dominance of intrapancreatic fat necrosis and acinar necrosis at the periphery of lobules. The findings observed were widely independent of the way of ethanol administration. The present approach offers a simple and reproducible animal model to study the influence of acute ethanol application on development of AP and hints on the involvement of disturbances of the pancreatic microcirculation and of acinar cell metabolism in the pathogenesis of ethanol-induced acute pancreatitis.

In Part I of this paper, features of alcoholic pancreatitis that are still poorly understood were reviewed and factors that might favor biliary-pancreatic reflux were summarized. Part II deals with additional pathogenetic schemes that might shed light on this perplexing disorder.

Changes in hepatic and pancreatic blood flow in response to ethanol infusion were determined simultaneously and continuously in anesthetized dogs, using a transit-time ultrasonic flowmeter and a laser-Doppler flowmeter. In addition, the effect of intravenous ethanol on exocrine pancreatic secretion was investigated. With a background infusion of secretin, ethanol (1.3 g/kg body wt) was infused intravenously over a 40-min period. Ethanol infusion significantly increased blood flow in the common hepatic artery (by 49%, at the time of the cessation of ethanol infusion), and this increased flow was maintained for 60 min after the cessation of ethanol infusion. In contrast, blood flow in the portal vein was not altered significantly by ethanol. Pancreatic blood flow and secretion showed no significant difference from those seen in the controls. Our data suggest that intravenous ethanol induces a redistribution of the splanchnic blood flow. The increased hepatic arterial flow seen in response to ethanol may play an important role in preventing ethanol-induced hypoxic liver damage.

Low doses of 95% ethanol (.03 ml/kg/min), infused intravenously into chronically instrumented lambs, rapidly caused severe pulmonary vasoconstriction and moderate systemic vasoconstriction at low blood alcohol levels. The effect of ethanol was dose dependent. Pulmonary vascular effects of 70% ethanol, but not of 95% ethanol were ameliorated by 100% oxygen. From these data, we speculate that ethanol may have a competitive interaction with the cellular mechanism(s) that transduce oxygen induced pulmonary vasodilation.

Alcohol may affect the integrity of the pancreatic parenchyma, as seen in alcoholic pancreatitis, some cases of chronic alcoholism without clinical pancreatitis, and experimental studies. The composition of pancreatic juice may reflect some of these changes. One type of parenchymal alteration is the loss of differentiative features of acinar cells, so that they take on the characteristics of ductular cells. Concomitant fibrosis completes the formation of the tubular complexes found in association with alcoholic chronic pancreatitis. Sustained alcohol intake may produce the accumulation of lipid droplets in parenchymal cells, some of which may be shown to be within the rough endoplasmic reticulum of acinar cells. Epithelial cells may undergo mucous metaplasia. The epithelial-basal lamina barrier frequently is breached in the area of intraluminal aggregates, with or without obvious inflammation in the immediate area. Loss of barrier function may lead to interaction among components of the external compartment (lumen) and the internal compartment (stroma). Increased levels of blood proteins and glycosaminoglycans in the juice, enzyme activation, fibrin formation, and complement activation are potential consequences of barrier loss. Increased lactoferrin levels could result in part from the activity and degranulation of polymorphonuclear leukocytes.

Alcohol has acute and chronic cardiovascular effects. Acutely, alcohol depresses cardiac function and alters regional blood flow. Even when withdrawn from alcohol for several days, alcoholics may still manifest evidence of left ventricular dysfunction. In some alcoholics a severe muscle disorder may ensue with the clinical features of a dilated cardiomyopathy. The concomitant presence of a thiamine deficiency or cirrhosis may produce hemodynamic changes that can obscure the clinical features of alcohol-induced heart muscle disease. Alcoholics may also develop acute myocardial infarction with patent coronary arteries; some may have cardiac arrhythmias even without other evidence of heart disease. Although epidemiological studies suggest that moderate users of alcohol have fewer coronary events than teetotalers, such studies also demonstrate a relation between alcohol abuse and hypertension and an increased occurrence of coronary disease. Thus, the injurious cardiovascular effects of alcohol must be considered when establishing recommendations for its use.