Pancreatic microcirculation in acute pancreatitis

We present a review of the microvascular morphology of the pancreas and microstructure of the pancreatic lobule, and report our experimental results of the investigation of pancreatic microcirculation following acute pancreatitis. Impairment of pancreatic microcirculation in the early phase of acute pancreatitis may play a key role in the progression of this disease. Possible contributory mechanisms include increased vascular permeability, reduced blood flow, leukocyte-endothelial cell interaction and intravascular thrombus formation. Using an in-vivo microscope system and off-line computer analysis, we achieved direct visualization and quantification of changes in microvascular permeability and leukocyte behavior in pancreas with acute pancreatitis. Bradykinin and oxygen radicals have been demonstrated to be involved in the increase of vascular permeability in the early stage of caerulein pancreatitis. Leukocyte adherence to the vessels in the pancreatic microcirculation is a secondary event following permeability changes in acute pancreatitis. Leukocyte infiltration during exacerbation of acute pancreatitis is mediated by leukocyte-endothelial cell interaction via leukocyte integrin CD11b/18. Received for publication on Jan. 29, 1997; accepted on April 24, 1997     

Microcirculatory derangement and ischemia of the pancreas]

We present a review of the microvascular morphology of the pancreas and microstructure of the pancreatic lobule, and introduce our experimental results on pancreatic microcirculation following acute pancreatitis. Impairment of pancreatic microcirculation in the early phase of acute pancreatitis may play a key role in the progression of this disease. Possible contributory mechanisms include increased vascular permeability, reduced blood flow, leukocyte-endothelial cell interaction, and intravascular thrombus formation. We achieved direct-visualization and quantification of changes in microvascular permeability and leukocyte behavior in the pancreas with acute pancreatitis using an in vivo microscope system and off-line computer analysis. Bradykinin and oxygen radicals have been demonstrated to be involved in the increased vascular permeability in the early stage of cerulein pancreatitis. Gabexate mesilate (FOY) prevents the increase in vascular permeability, resulting in a decreased number of rolling leukocytes. Leukocyte adherence to the pancreatic microcirculation is a secondary event following permeability changes in acute pancreatitis. Leukocyte infiltration during aggravation of acute pancreatitis is mediated by leukocyte-endothelial cell interaction via leukocyte integrin CD11b/18. The diamino-pyridine derivative IS-741 inhibits the progression of pancreatic inflammation by down-regulating the expression of CD11b/18.     

Potential effects of hyperbaric oxygen therapy in acute pancreatitis

BACKGROUND: To extract from the biomedical published reports, the effects of hyperbaric oxygen (HBO) on inflammatory disease, in particular acute pancreatitis. METHODS: This review will explain these effects and evaluate potential mechanisms of action of HBO in acute pancreatitis. A Medline/PubMed search (January 1966 to July 2004) with manual cross-referencing was conducted, including all relevant articles investigating the molecular and systemic effects of HBO on inflammatory diseases, particularly focusing on the studies of acute pancreatitis. All publication types, languages and subsets were searched. RESULTS: Original and review articles and short communications were extracted. The selected original articles covered the molecular and systemic effects of HBO and the effects in inflammatory disease states. The major findings are that HBO can act as an anti-inflammatory agent and as an antimicrobial agent. Many of the effects of HBO would be beneficial in the treatment of acute severe pancreatitis. Work carried out to date in animal models of acute pancreatitis shows promising improvements in severity but studies are limited to date. CONCLUSION: Acute pancreatitis impairs the pancreatic and systemic microcirculation and causes acute inflammation. These processes are potentially improved by HBO therapy.     

Early microcirculatory derangement in mild and severe pancreatitis models in mice

An in vivo microscopic technique was used to clarify the increase in microvascular permeability and enhanced leukocyte–endothelium interaction of pancreatic microcirculation in experimental pancreatitis of differing severity. Using bovine albumin fluorescein isothiocyanate (FITC) and carboxyfluorescein diacetate succinimidyl ester (CFDASE) as tracers, the change in permeability and the behavior of leukocytes in the acinar microcirculation were quantified during the initial 1, 2, 6, and 12 h after the induction of caerulein pancreatitis in mice. Cold stress was added to produce the severe model. It was revealed that the early microcirculatory changes in the pancreas of caerulein pancreatitis included the increased permeability of endothelial lining and an accumulation of extravasated fluid in the perilobular space, which were more severe if cold stress was added. A decrease in flow velocity was also noted 2 h after the onset of severe pancreatitis. Leukocyte adherence to the endothelial cells was not observed during the first 12 h in either model of severity. In contrast, observation of the hepatic microcirculation revealed a significant number of adherent leukocytes 2 h after the induction of severe pancreatitis. These results suggest that during the early course of acute pancreatitis, leukocyte adherence in the pancreatic microcirculation is a secondary event following the increase in pancreatic vascular permeability. Received: February 21, 2000 / Accepted: March 6, 2001     

改善微循环和防止细胞钙超载在阻止急性胰腺炎重症化治疗中的作用

目的 探讨改善胰腺缺血和防止钙超载在阻止急性胰腺炎理症化治疗中的作用。方法 报道278例急性胰腺炎（AP）的治疗及体会。第一阶段（1990年1月至1994年12月）采取常规非手术治疗，第二阶段（1995年1月至1999年12月）采取改善微循环和防止细胞钙超负荷的措施。结果 后阶段的治疗方案可明显降低轻型胰腺炎向重症胰腺炎的转化率，减少全身并发症发生率，降低死亡率，缩短治愈时间。结论 重点改善胰腺缺血和防止细胞钙超负荷的治疗有助于阻止AP由轻型向重型的发展，限制胰腺坏死，改善AP预后。     

遏制轻型急性胰腺炎向重症转化的非手术 治疗策略

目的 ：探讨遏制急性胰腺炎向重症转化的非手术治疗策略。方法 ：将4年间收治的286例轻型急性胰腺炎分为对照组和治疗观察组。对照组采取常规非手术治疗措施;观察组加用改善胰腺微循环，防治细胞钙超载和抑制胰酶的治疗方法。结果 ：对照组144轻型有20例转化为重症胰腺炎，14例发生全身性并发症;观察组142例轻型有8例转化为重症，2例出现全身性并发症。观察组重症患者血C-反应蛋白和Balthazar CT严重度指数在治疗后各时点较对照组明显降低。结论 ：在常规治疗的基础上加用改善胰腺微循环，防治细胞钙超载和抑制胰酶的治疗措施可能有助于阻止轻型急性胰腺炎向重症化发展。     

急性胰腺炎早期胰腺微循环的改变

目的 探讨急性胰腺炎时胰腺微循环的变化。方法 采用文献回顾的方法．对有关急性胰腺炎时胰腺微循环变化进行综述。结果 在急性胰腺炎早期．胰腺微循环发生了一系列变化。主要表现为微血管收缩，血流速度减慢．血管壁通透性升高，白细胞在毛细血管后小静脉壁上黏附，胰腺灌注量减少等。结论 急性胰腺炎早期胰腺微循环紊乱在胰腺炎的发生、发展中起重要作用。     

Systemic intravenous infusion of bovine hemoglobin significantly reduces microcirculatory dysfunction in experimentally induced pancreatitis in the rat

OBJECTIVE: To evaluate the effectiveness of bovine hemoglobin on pancreatic microcirculation and outcome in experimental acute rodent pancreatitis. SUMMARY BACKGROUND DATA: Stasis of the pancreatic microcirculation initiates and aggravates acute pancreatitis. Hydroxyethyl-starch (HES) has been shown to improve pancreatic microcirculation. Similarly, bovine hemoglobin might improve rheology due to its colloid effect, but additionally supplies oxygen to oxygen depleted pancreatic tissue. METHODS: In Wistar rats, severe acute pancreatitis was induced by administration of glucodeoxycholic acid i.d. and cerulein i.v. Pancreatic microcirculation was continuously monitored by fluorescence microscopy. Fifteen minutes after the initiation of acute pancreatitis, animals received either 0.8 mL bovine hemoglobin (Oxyglobin), HES, or 2.4 mL 0.9% NaCl i.v. at random. After 6 hours, animals were killed and histopathological damage of the pancreas was assessed using a validated histology score (0-16). RESULTS: In comparison to controls, pancreatic microcirculation improved significantly in the HBOC group (mean difference of capillary density 31.4%; standard error 5.6%; P < 0.001; 95% confidence interval for difference 17.5-45.3). HES was not as effective as HBOC substitution. The histology score revealed less tissue damage in the HBOC group [6.25 vs. 9.25 (3-8.5 vs. 8-10.75, P < 0.001)] in comparison to controls and also in comparison to the HES group [6.25 vs. 8 (3-8.5 vs. 6.5-10.25, P < 0.006)]. CONCLUSIONS: In severe acute pancreatitis, single i.v. injection of bovine hemoglobin improves pancreatic microcirculation and reduces tissue damage.     

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.     

Factors involved in the pathogenesis of acute pancreatitis

Pathophysiological and molecular research have marked the understanding of the primary events taking place in triggering acute pancreatitis, although the early diagnosis of pancreas diseases in general, continues to be a source of frustration in modem medicine. This presents the news about pathogenesis (co-localization theory, auto-activation theory of the tripsynogen), location of early events (acinar pancreatic cells which are the "key" involved: muscarinic receptors, acinar membrane, role of ionized calcium, the phenomenon of apoptosis), extracellular events in initiation of acute pancreatitis with the granting of a central place to enzyme activation and systemic inflammatory response. Aspects of early microvascular changes, disturbances of ischemia-reperfusion and systemic microvascular abnormalities are so important that justifies therapeutic concept of microcirculatory protection. Participation of monocyte/macrophage system, excessive activation of leukocytes that involving activation and release of lysosomal enzymes and oxygen free radicals associated with ischemia-reperfusion mechanism are defining for pathogenesis of acute pancreatitis.     

Endothelin receptor antagonists are not beneficial in the therapy of acute experimental pancreatitis

BACKGROUND AND AIM: Due to increased capillary permeability and the early appearance of vasoactive and toxic agents, patients suffering from necrotizing pancreatitis frequently develop a systemic inflammatory response syndrome (SIRS). Endothelin, a potent vasoconstrictor, is thought to play a major role in these changes via the regulation of microcirculation. An improved outcome of acute experimental necrotizing pancreatitis by blocking the endothelin receptors ETA and ETB, either selectively (only ETA) or unselectively (ETA and ETB), has been suggested. The aim of this study was to investigate further the beneficial effects of new, highly potent endothelin-receptor (ET-R) antagonists in acute experimental pancreatitis. METHODS: The influence of the selective ET-RA antagonist BSF208075 (1 mg/kg) on mortality was studied in three severity groups of acute necrotizing pancreatitis (retrograde injection of 4%, 5% and 6% of sodium taurocholate into the main pancreatic duct). The effects of the selective ET-RA antagonists LU135252 (LU13) and BSF208075 (BSF20) and of the unselective endothelin receptor (ET-R(A/B)) antagonist BSF420627 (BSF42) were additionally analyzed in 4% taurocholate-induced necrotizing pancreatitis. Furthermore, the significance of variable doses of the endothelin receptor antagonist LU13 (1 mg/kg, 3 mg/kg and 100 mg/kg) was determined in a 4% sodium taurocholate model and in a cerulein pancreatitis model. RESULTS: Prophylactic ET-R antagonism increased the mortality rate in the 4% sodium taurocholate-induced pancreatitis. No reduction in pancreatic damage after induction of taurocholate pancreatitis was found by ET-R blockage. Application of ET-R antagonists had no beneficial influence in ascites development. However, administration of LU13 (100 mg/kg) resulted in a non-significant increase in pancreatic oedema, whereas peritoneal necrosis was not affected. CONCLUSION: The selective and unselective ET-R antagonists BSF20, BSF42 and LU13 failed to improve survival and pancreatic damage during acute experimental pancreatitis. Therefore, previously reported beneficial effects of ET-R antagonists in experimental acute pancreatitis have to be critically evaluated before conclusions for further clinical development are made.     

Pancreatic capillary blood flow in an improved model of necrotizing pancreatitis in the rat

INTRODUCTION: The development of acute pancreatitis is characterized by profound changes in pancreatic microcirculation. Using in vivo microscopy with fluorescent-labeled erythrocytes as tracers we studied changes in pancreatic microcirculation in an improved rat model of necrotizing pancreatitis (NP) in comparison to edematous pancreatitis (EP) and healthy controls. METHODS: Twenty-one male Wistar rats had their pancreatae exteriorized in a temperature-controlled immersion chamber followed by intravenous administration of fluorescent-labeled autologous erythrocytes. EP was induced by intraductal saline and intravenous caerulein (5 microg/kg/h) for 6 h (n = 7) and NP by controlled intraductal infusion of glycodeoxycholic acid (10 mmol/L) followed by intravenous caerulein (n = 7). Control animals received intraductal and intravenous saline (n = 7). The determination of pancreatic microcirculation was performed before as well as 1, 3, and 6 h after intraductal infusion by correlating the number of passing labeled erythrocytes/capillary/min with their concentration per microliter of arterial blood. RESULTS: Pancreatic capillary flow in control animals remained constant over the 6-h observation period. Pancreatic capillary flow in the EP group rapidly increased to 188% of baseline after 3 h and remained significantly elevated throughout the experiments (P = 0.0001). In contrast, pancreatic capillary flow decreased significantly in the group suffering NP with values 46.7% of baseline after 6 h (P = 0.0001). Complete capillary stasis developed in 38% of investigated capillaries in the NP group compared to 0-1% in both other groups (P = 0.0001). CONCLUSION: Pancreatic microcirculation in mild edematous pancreatitis is significantly increased while the evolution of necrotizing pancreatitis in the model studied herein is characterized by a dramatic reduction in pancreatic capillary flow in conjunction with areas of capillary stasis. These results underline the pathophysiologic relevance of the model and of therapeutic measures aimed at an improvement of pancreatic microcirculation in clinical necrotizing pancreatitis.     

Therapeutic effect of isovolemic hemodilution with dextran 60 on the impairment of pancreatic microcirculation in acute biliary pancreatitis.

Dextran of different molecular weight (Dx 40, Dx 60/70) has often been evaluated as adjunct treatment of experimental acute pancreatitis. A beneficial effect has been documented by a decrease in its lethality. However, the mechanism of action is poorly understood. A specific effect on the pancreatic microcirculation generally has not been documented and differentiation from unspecific improvement of pancreatic blood flow due to volume expansion has been difficult. This investigation was designed to quantify the effect of dextran on the impairment of pancreatic microcirculation during acute biliary pancreatitis by means of intravital microscopy. Dextran 60 (Dx 60, molecular weight 60,000) was chosen in light of the increase in vascular permeability in the early stage of pancreatitis as demonstrated previously in the same model. Isovolemic hemodilution, i.e., exchange of whole blood for Dx 60 was used as a mode of administration to achieve instantaneous onset of therapy without changes in intravascular volume. In the control group a progressive reduction of pancreatic capillary perfusion commenced 30 minutes after induction of acute pancreatitis, resulting in cessation of nutritive tissue perfusion after 3 hours. In the animals subjected to hemodilution, stabilization of the pancreatic microcirculation was accomplished throughout the observation period of 6 hours. Because volume-related effects could be excluded by the protocol and by monitoring central venous pressure and hematocrit, a specific effect of hemodilution with DX 60 on the pancreatic microcirculation is indicated by our results.     

Pancreatic ischaemia in experimental acute pancreatitis: mechanism, significance and therapy

Much clinical and experimental evidence suggests that pancreatic ischaemia in the early phase of acute pancreatitis is important in the development of pancreatic necrosis. While depletion of intravascular volume has often been assumed to be the main circulatory defect, an additional disturbance of pancreatic microcirculation has been demonstrated experimentally. Possible contributory mechanisms include chemical-induced vasoconstriction, direct injury of vessel wall, intravascular coagulation and increased endothelial permeability resulting in pancreatic oedema, haemoconcentration and impaired venous drainage. Pancreatic ischaemia as a consequence of these local effects seems to be responsible for the transition of mild pancreatitis to parenchymal necrosis. In experimental models the beneficial effect of various drugs and of sympathetic blockade has been ascribed to an improvement in pancreatic perfusion. Although effective volume therapy is generally accepted as the mainstay of conservative treatment in acute pancreatitis, the efficacy of different fluid preparations is still controversial, and simple fluid resuscitation has not been shown to prevent the development of parenchymal necrosis. The specific impairment of pancreatic microcirculation cannot be prevented merely by replenishment of intravascular volume with crystalloids, albumin or plasma despite normalization of macrohaemodynamics. In contrast, partial replacement of blood by dextran preparations has been shown to increase pancreatic perfusion by improving blood fluidity. Isovolaemic haemodilution in conjunction with conventional fluid therapy may provide a new and effective means of protecting the pancreas from secondary injury due to the early ischaemic phase of acute pancreatitis.     

Treatment of acute pancreatitis with beta-adrenergic agonist drugs

An increase in microvascular permeability may be important in the pathogenesis of acute pancreatitis. beta-adrenergic receptor agonist drugs are known to inhibit the increase in microvascular permeability induced by histamine and related vasoactive substances. These inflammatory mediators have been shown to be released during the course of experimental and human pancreatitis. We investigated the effect of isoproterenol and terbutaline sulfate on the development of acute edematous (AEP) and acute hemorrhagic (AHP) pancreatitis in a feline model of biliary pancreatitis. When given at the time of pancreatic insult, isoproterenol prevented the development of both AEP and AHP. Both isoproterenol and terbutaline sulfate reduced the severity of pancreatic inflammation, even when given up to 12 hours after the onset of AEP. Although neither drug was effective in treating established AHP, our findings suggest that, if given early in the course of the disease, they may be useful in preventing the progression of AEP to AHP.     

急性胰腺炎外周循环和胰腺微循环血小板内皮细胞粘附分子-1的表达

目的　探讨急性胰腺炎 (AP)外周循环和胰腺微循环中血小板内皮细胞粘附分子 1(PECAM 1)表达的变化规律。方法　Wistar大鼠 48只 ,诱发AP动物模型 ,用流式细胞仪分析脾静脉和下腔静脉血中多形核白细胞 (PMN )PECAM 1的表达。结果　 ( 1)在急性水肿性胰腺炎(AEP)动物模型中 ,外周循环和胰腺微循环PMNPECAM 1的表达水平在AEP 2、4h组相近 ,自 4h开始 ,外周循环PMNPECAM 1的表达上调直至 8h ;胰腺微循环PMNPECAM 1的表达下调直至 8h ,在AEP 8h组 ,差异有显著性 ( P <0 .0 5 )。 ( 2 )在急性坏死性胰腺炎 (ANP)模型中 ,胰腺微循环PMNPECAM 1的表达下调 ;外周循环组PMNPECAM 1的表达未见明显变化 ,在ANP 4、6h组 ,差异有显著性 (P <0 .0 5 )。结论　AEP胰腺微循环和外周循环PMNPECAM 1的表达呈逆向性 ,在胰腺微循环呈下调趋势 ,在外周循环呈上调趋势 ;ANP胰腺微循环PMNPECAM 1的表达呈加速性下调 ,该结果显示 ,在ANP早期 ,抑制PMNPECAM 1的过度表达可能有助于改善AP病理改变。     

The relative safety of MRI contrast agent in acute necrotizing pancreatitis.

OBJECTIVE: To validate the safety of gadolinium-diethylenetriamine pentaacetic acid (GD-DTPA) by measuring its effect on pancreatic capillary perfusion and acinar injury in acute pancreatitis. BACKGROUND: Contrast-enhanced computed tomography (CECT) is proposed as a gold standard for early evaluation of acute necrotizing pancreatitis. However, iodinated contrast media used for CECT have been shown in these circumstances to reduce pancreatic capillary flow and increase necrosis and mortality. Recent reports suggest that post-GD MRI provides images comparable to CECT in the assessment of severe acute pancreatitis. METHODS: Necrotizing pancreatitis was induced in 14 Wistar rats by intraductal glycodeoxycholic acid (10 mM/L) and intravenous caerulein (5 microg/kg/h) over 6 hours. Intravital microscopic quantitation of pancreatic capillary blood flow was performed using fluorescein isothiocyanate-labeled erythrocytes after induction of pancreatitis and 30 and 60 minutes after an intravenous bolus of either Ringer's solution or GD-DTPA (0.2 mL/kg). RESULTS: The two study groups were comparable with regard to mean arterial pressure, heart rate, arterial blood gases, hematocrit, amylase, lipase, and trypsinogen activation peptide production throughout the experiment. GD-DTPA did not reduce capillary flow (1.93 +/- 0.05 nL/capillary/min) compared to animals infused with Ringer's solution (1.90 +/- 0.06 nL/capillary/min). CONCLUSIONS: Intravenous injection of GD-DTPA does not further impair pancreatic microcirculation or increase acinar injury in acute necrotizing pancreatitis. Because of this advantage over CT contrast medium, further development of MRI as a staging tool in acute pancreatitis seems desirable.     

Importance of microcirculatory disturbances in the pathogenesis of pancreatitis.

Pancreatic microvascular control is a complex physiological process which is incompletely understood. Blood flow in the pancreas is altered by a large number of endogenous and exogenous factors in the context of acute and chronic pancreatitis. The frequency of progression from acute pancreatitis to a chronic form is a controversial question. In acute pancreatitis reductions in blood flow and alterations of microvascular integrity resulting in impaired tissue oxygenation play an important part in the progression and possibly the initiation of the disease. Endothelin and nitric oxide are believed to be two of the most effective vasoactive mediators. The beneficial effect of therapeutic strategies affecting vasoactive mediators is confirmed in experimental studies. Chronic disease is associated with decreased pancreatic blood flow and histological changes in the vasculature in both patients and animal models. Further studies are needed to clarify whether ischemia in chronic pancreatitis is more important in perpetuating the disease or as primary cause of the inflammatory processes.     

Metabolic Management of Severe Acute Pancreatitis

The metabolic management of severe acute pancreatitis involves early identification of patients with severe pancreatitis, aggressive fluid resuscitation, organ support, and careful monitoring in an intensive care environment. Recent evidence has helped to define the roles of enteral feeding, prophylactic antibiotics, endoscopic retrograde cholangiopancreatography, computed tomography, and fine-needle aspiration for bacteriology. The most difficult decision in the management of these patients is whether surgery is required and which of the complementary approaches to necrosectomy and drainage is appropriate. Key metabolic events in the acinar cell, pancreas, and intestines are now being unraveled, as is the basis for the systemic manifestations and organ dysfunction associated with pancreatitis. This gives hope for the development of more specific metabolic interventions, which will likely target the maintenance of intestinal integrity and function, preservation of pancreatic microcirculation, and balanced modulation of the inflammatory response.     

Renal microcirculation in experimental acute pancreatitis of dogs--the effect of pancreatic protease inhibitor and dopamine

To understand the renal microcirculation in acute pancreatitis is important to know the pathophysiology of renal insufficiency frequently observed as one of multiple organ failures in severe acute pancreatitis. In mongrel dogs acute pancreatitis was experimentally introduced by autologous bile added trypsin injection into the pancreatic duct. The effect of new synthesized pancreatic protease inhibitor (PATM) and dopamine in a dose of 3mg/kg/hr and 10 micrograms/kg/min were investigated, respectively. In acute pancreatitis dogs, renal arterial blood flow and renal tissue blood flow immediately fell and gradually decreased in time course of experiment and renal vascular resistance increased from 2 hours after onset of pancreatitis. When pancreatic protease inhibitor (PATM) was infused in acute pancreatitis dogs, blood pressure and pulse pressure relatively preserved during the experiment. Renal blood flow and renal tissue blood flow were maintained during the first 1 hour and thereafter slightly decreased, however which was less than that of no PATM treated dogs. When dopamine was infused in acute pancreatitis dogs, blood pressure was maintained during the first 90 minutes thereafter remarkably decreased. Renal blood flow was maintained within 60 minutes, however it remarkably decreased at the end of the experiment. This study suggested that renal microcirculation was disturbed from early period of acute pancreatitis in dogs and pancreatic protease inhibitor (PATM) had a beneficial effect of maintain the renal microcirculation.