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     

Pancreatic microcirculation in acute pancreatitis of dogs

Pancreatic microcirculation in acute pancreatitis and the effect of dopamine and pancreatic protease inhibitor were investigated in 35 mongrel dogs. Acute pancreatitis was induced by the injection of autologous bile added trypsin into pancreatic duct. In acute pancreatitis dogs femoral artery pressure and pulse pressure gradually decreased and pancreatic microflow in basal state temporarily increased immediately after bile injection, however, thereafter continuously decreased during the experiments. Portal flow severely decreased just after onset of acute pancreatitis. By administration of dopamine femoral artery pressure was maintained during the first 90 minutes of experiments, however, thereafter decreased until the end of experiments. Pancreatic microflow, 56.1 +/- 15.3 ml/min/100g in basal level was shown 66.1 +/- 13.7 and 60.3 +/- 10.3 ml/min/100g at 1 and 2 hours, respectively, after bile injection, which were significantly high values as compared with those of non dopamine administration. However those values decreased at 5 hours of both experiments. Portal flow whose basal level was 237 +/- 67 ml/min was maintained during the first 1 hour however it decreased to 139 +/- 25 ml/min at 5 hours. By administration of pancreatic protease inhibitor femoral artery pressure and pulse pressure, temporarily decreased immediately after bile injection, however, they were maintained thereafter. Pancreatic microflow, 57.1 +/- 18.3 ml/min/100g in basal level, was maintained during the first 2 hours, however significantly decreased to 27.6 +/- 9.7 ml/min/100g at 5 hours. Portal flow significantly increased to 442 +/- 115 ml/min at 2 hours, however, thereafter decreased 219 +/- 93 ml/min at 5 hours.(ABSTRACT TRUNCATED AT 250 WORDS)     

重症急性胰腺炎微循环障碍的治疗现状

胰腺微循环障碍是导致急性胰腺炎发展的重要因素,其在重症急性胰腺炎发病中的作用越来越引起人们的重视,针对改善胰腺微循环的治疗方法会减少胰腺组织的坏死程度和病变的演进。本文针对重症急性胰腺炎微循环障碍提出相关的治疗策略。     

腹膜透析对急性重症胰腺炎大鼠胰腺微循环的影响

目的：探讨腹膜透析（PD）对急性重症胰腺炎（ASP）大鼠胰腺微循环的影响。方法：SD大鼠72只随机分为对照组（24只）、ASP组（24只）和ASP加PD组（24只）；观察各组血清血栓素A2／前列腺素（TXA2／6-K．PGF1a）和内皮素（ET—1）水平，以及胰腺血流波幅和胰腺病理变化。结果：ASP组和PD组血清ET-1水平较对照组明显升高；在同时段病例中，ASP组与加PD组比较，后者的水平明显降低；ASP组和加PD组血清TXA2／6-K—PGF1a水平较对照组明显升高：同时段ASP组与加PD组比较，后者的水平明显降低。ASP组胰腺血流波幅明显降低，加PD治疗后波幅有显著提高。加PD组大鼠的胰腺病理损害较ASP组明显减轻。结论：微循环障碍是ASP的重要病理生理基础．早期行PD治疗能有效地改善ASP所致之血微循环障碍，对胰腺有保护作用。     

中药复方“清下1号”对急性水肿性胰腺炎局部微循环损伤的作用

目的探讨大鼠急性水肿性胰腺炎(AEP)动物模型的早期微循环改变及中药复方清下1号（MCP-1）对AEP胰腺微循环的作用。方法用异硫氰酸荧光素-荧光标记红细胞(FITC-RBC)胰腺活体微循环技术、微血管树脂/墨汁灌注光镜和扫描电镜、透射电镜技术,用蛙皮缩胆囊肽诱发大鼠急性胰腺炎（AP）动物模型,观察36只Wistar大鼠的早期微循环改变、MCP-1应用后胰腺局部微循环的反应。结果与AEP自然病程组比较,MCP-1治疗组血清淀粉酶由（2997.7±801.4）?IU/L降至（1909.7±295.5）?IU/L（P<0.01）;胰腺间质炎性细胞浸润减少;腺泡细胞胞浆内空泡减少;毛细血管密度由（52.8±6.1）%增至（63.2±5.5）%（P<0.01);微血管管径由（4.5±0.4）?μm增至（5.9±0.6）?μm（P<0.05）;FITC-RBC显示胰腺微循环流速、流量增加,灌流稳定(0.87±0.06)nl/min（P<0.01)。结论MCP-1具有显著改善AP胰腺微循环的作用,抗AP胰腺局部微循环损伤是实现MCP-1疗效的重要机制。     

吞噬刺激素及其抑制物对急性胰腺炎胰腺微循环的影响

目的探讨在急性胰腺炎 (acutepancreatitis,AP)发展过程中吞噬刺激素及其抑制物对胰腺微循环的影响。方法SD大鼠每组 2 4只 ,分别为对照组、吞噬刺激素组、AP组、AP 吞噬刺激素组、AP 吞噬刺激素抑制物组。按随机原则在 0、3、6、12h分批处死大鼠 ,光镜下观察胰腺病理改变程度 ,纤维素染色观察微血栓情况 ,计数微血栓数量。结果对照组与吞噬刺激素组在不同时段微血栓数量之间差异均无显著意义 ;3、6、12h各组微血栓数量均比对照组和吞噬刺激素组明显升高 ;AP组、AP 吞噬刺激素组、AP 吞噬刺激素抑制物组在 3、6、12h各时间段之间比较微血栓数量逐渐增加 ,差异均有显著意义 ;AP 吞噬刺激素组在各时间段均较AP组微血栓数量明显增加 ;AP 吞噬刺激素抑制物组在 6、12h微血栓数量明显减少 ,与AP组比较差异有显著意义。结论AP时吞噬刺激素促使胰腺微血栓数量增加 ,应用吞噬刺激素抑制物可使胰腺微循环状态明显改善     

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。     

Intestinal microcirculation and gut permeability in acute pancreatitis: Early changes and therapeutic implications

Translocation of bacteria from the intestine causes local and systemic infection in severe acute pancreatitis. Increased intestinal permeability is considered a promoter of bacterial translocation. The mechanism leading to increased gut permeability may involve impaired intestinal capillary blood flow. The aim of this study was to evaluate and correlate early changes in capillary blood flow and permeability of the colon in acute rodent pancreatitis of graded severity. Edematous pancreatitis was induced by intravenous cerulein; necrotizing pancreatitis by intravenous cerulein and intraductal glycodeoxycholic acid. Six hours after induction of pancreatitis, the permeability of the ascending colon was assessed by the Ussing chamber technique; capillary perfusion of the pancreas and colon (mucosal and subserosal) was determined by intravital microscopy. In mild pancreatitis, pancreatic capillary perfusion remained unchanged (2.13 ± 0.06 vs. 1.98 ± 0.04 nl-min^−l.cap ⁻¹ [control]; P = NS), whereas mucosal (1.59 _± 0.03 vs. 2.28 ± 0.03 nl.min^−l.cap ⁻¹ [control]; P <0.01) and subserosal (2.47 ± 0.04 vs. 3.74 ± 0.05 nl-min^−l.cap ^-1 [control]; P <0.01) colonic capillary blood flow was significantly reduced. Severe pancreatitis was associated with a marked reduction in both pancreatic (1.06 = 0.03 vs. 1.98 ± 0.04 nl’min^-1.cap ^-1 [control]; P <0.01) and colonic (mucosal: 0.59 = 0.01 vs. 2.28 ± 0.03 nl.min^−l.cap ^-1 [control], P < 0.01; subserosal: 1.96 ± 0.05 vs. 3.74 ± 0.05 nl.min^−l.cap ^-1 [control], P <0.01) capillary perfusion. Colon permeability tended to increase with the severity of the disease (control: 147 ±19 nmol.hr^−l.cm {−2}2; mild pancreatitis: 158±23 nmol-hr^−l.cm^-2; severe pancreatitis: 181 ±33 nmol.hr^−l.cm^-2; P = NS). Impairment of colonic capillary perfusion correlates with the severity of pancreatitis. A decrease in capillary blood flow in the colon, even in mild pancreatitis not associated with significant protease activation and acinar cell necrosis or impairment of pancreatic capillary perfusion, suggests that colonic microcirculation is especially susceptible to inflammatory injury. There was no significant change in intestinal permeability in the early stage of pancreatitis, suggesting a window of opportunity for therapeutic interventions to prevent the later-observed increase in gut permeability, which could result in improved intestinal microcirculation. Presented at the Thirty-Seventh Annual Meeting of The Society for Surgery of the Alimentary Tract, San Diego, Calif., May 19–22, 1996. Supported in part by Deutsche Forschungsgemeinschaft (DFG Fo 197/3).     

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.     

早期改善胰腺微循环对重症急性胰腺炎的影响

目的　探讨早期改善胰腺微循环对治疗重症急性胰腺炎 (SAP)的疗效。方法　回顾性分析对比 1995～ 1998年 44例 (前期 )和 1998～ 2 0 0 1年 40例 (后期 )SAP患者的治疗效果。前期采取常规统一治疗 ,后期增加改善胰腺缺血及防止细胞钙超负荷的措施。结果　后期患者治愈率(85 .0 % )显著高于前期SAP患者治愈率 (68.2 % ) (P <0 .0 5 ) ;后期死亡率 (15 .0 % )、中转手术率(2 2 .5 % )、并发症率 (3 5 .0 % )明显地低于前期 (3 1.8%、40 .9%、5 4.5 % ) (P <0 .0 5 )。后期平均住院日 (2 2± 4)d ,较前期平均住院日 (3 2± 7)d明显缩短 (P <0 .0 5 )。结论　改善胰腺缺血和防止细胞钙超负荷有助于限制SAP恶化进程 ,改善SAP的预后     

急性胰腺炎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)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血中白细胞PECAM 1的表达。结果　与正常组相比 ,各实验组多形核白细胞 (PMN)PECAM 1的表达下调 ,在急性坏死性胰腺炎 (ANP)组差异有显著性 ,ANP 2h组 [(63 .0± 1 9.2 ) % ,P <0 .0 5] ,ANP 4、6h组[(38.1± 2 1 .2 ) %、(32 .9± 1 4 .5) % ,P <0 .0 0 1 ] ;淋巴细胞PECAM 1的表达轻度下调 ,差异无显著性(P >0 .0 5)。结论　胰腺微循环中PMNPECAM 1表达的下调说明PMN的激活 ,可促进PMN外渗 ;抑制PMNPECAM 1的过度表达可能是治疗AP和 /或阻断AP向坏死型转化的一种潜在途径     

急性胰腺炎微循环障碍的研究现状

微循环既是血液循环系统的末梢部分，又是许多器官独立的功能单元。对急性胰腺炎微循环的研究，起步虽然较晚，但近几年发展迅猛。     

尿激酶区域动脉灌注对重症急性胰腺炎大鼠胰腺微循环的影响

目的探讨尿激酶区域动脉灌注（LAI）对重症急性胰腺炎（SAP）大鼠微循环的影响.方法将1 20只大鼠随机分成4组,每组40只.A组为假手术组（S组）;B组为SAP组;C组为SAP尿激酶LAI组;D组为SAP生理盐水LAI组（对照组）.以激光多普勒检测大鼠胰腺血流量,以伊文思蓝（Evans Blue）漏出率检测胰腺微循环血管的通透性,同时观察胰腺病理变化.结果（1）胰腺血流量（PBF）：A组1 h和3 h的胰腺PBF高于其他3组,差异有显著性（均P＜0.05）;B组1 h和3h的PBF与D组差异无显著性;C组1 h和3h的PBF明显高于B组和D组（P＜0.05）.（2）EB漏出率：B,C,D组胰腺组织EB的漏出率显著高于A组（均P＜0.05）,但B,C,D组之间无统计学差异（均P＞0.05）.（3）胰腺组织病理评分：术后1,3 h时,C组评分明显高于A组（P＜0.05）,但明显低于B,D组（均P＜0.05）,B,D组之间无明显差异（P＞0.05）.结论尿激酶LAI能改善SAP大鼠胰腺微循环,但不能完全阻止SAP的病理演变.     

Pulmonary microcirculation in mild and severe experimental pancreatitis

BACKGROUND: Research aimed at elucidating the pathogenesis of pancreatitis-associated lung injury and evaluating novel strategies for preventing respiratory complications in acute pancreatitis (AP) has not yet involved intravital microscopic (IVM) studies of pulmonary microcirculation in animals with severe disease. OBJECTIVE: To characterize and compare pulmonary microcirculation in severe/necrotizing (NP) and mild/edematous pancreatitis (EP) in the rat. METHODS: EP was induced by intravenous cerulein infusion (n = 10) and NP by a standardized intraductal infusion of glycodeoxycholic acid followed by intravenous cerulein (n = 10). After 24 h a left-sided thoracotomy was performed for IVM examination of pulmonary capillary blood flow, permeability, leukocyte sticking and the thickness of alveolar septi. Further measurements included monitoring of arterial blood gases and histological evaluation of lung injury. RESULTS: In animals with NP, histology revealed severe pulmonary edema together with clustering of polymorphonuclear leukocytes in pulmonary microvessels and alveoli. IVM showed a greater number (n) of leukocytes sticking on the endothelium of pulmonary capillaries (9.4 +/- 0.7 vs. 1.8 +/- 0.2 in healthy control animals) and increased capillary permeability (260 +/- 14 vs. 136 +/- 6% relative fluorescein intensity) while capillary blood flow was decreased (0.41 +/- 0.05 vs. 0.57 +/- 0.03 mm/s). In comparison, changes in EP were significantly less pronounced (flow 0.5 +/- 0.04 mm/s, permeability 156 +/- 4%, leukocyte sticking n = 4.6 +/- 0.7). CONCLUSIONS: These findings suggest that deterioration of pulmonary microcirculation in AP correlates with disease severity and that a model featuring NP may therefore be more suitable to further study pancreatitis-associated pulmonary injury.     

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.     

磺达肝癸钠对高脂血症急性坏死性胰腺炎大鼠微循环及炎症因子影响

目的探讨磺达肝癸钠对高脂血症急性坏死性胰腺炎大鼠微循环及炎症因子影响。方法以健康SD雄性大鼠30只为研究对象,抽签法随机分为治疗组(n=15)和高脂血症组(n=15),两组均通过喂养高脂饲料建立高脂血症大鼠模型,此外治疗组通过将0.1 m L/100 g体重的5%的牛黄胆酸钠溶液注入胰胆管内制成急性坏死性胰腺炎模型,并在建模后0 h、6 h、12 h、18 h注射0.2 m L/100 g次璜达肝癸钠。两组建模后均禁食、禁饮并行2 m L/100 g生理盐水补液。治疗组分别于治疗前和治疗24 h取静脉血用于血清IFN-γ、TNF-α,IL-6和IL-10等炎症因子水平检测,并在治疗前、治疗6 h、12 h和24 h检查比较两组胰体头部和尾部微区血流量。两组建模24 h后均处死剖腹,观察腹腔内组织和胰腺情况,并切除十二指肠内侧胰腺组织行病理检查。结果与高脂血症组比较,治疗组治疗前血清IFN-γ、TNF-α,IL-6和IL-10等炎症因子水平均升高(P0.05)。与治疗前比较,治疗组治疗24 h血清炎症因子水平均降低(P0.05)。与高脂血症组比较,治疗组治疗6 h、12 h和24 h胰体头部和尾部微区血流量均升高(P0.05)。与治疗前比较,治疗组治疗前、治疗6 h、12 h和24 h胰体头部和尾部微区血流量则升高(P0.05)。治疗组水肿、坏死、炎性细胞浸润等胰腺组织病理学评分均高于高脂血症组(P0.05)。结论磺达肝癸钠可改善大鼠微循环及炎症状态。     

Contrast-enhanced computed tomography in acute pancreatitis: does contrast medium worsen its course due to impaired microcirculation?

Background An early and accurate diagnosis of severe acute (necrotizing) pancreatitis is important to allow timely institution of therapy to limit the extra-pancreatic sequelae of this necrotizing process and to minimize the incidence of super-infection of the necrosis (i.e., progression to infected necrosis). Contrast-enhanced computed tomography (CECT) has become the cornerstone of diagnosis by confirming the clinical diagnosis of severe acute pancreatitis based on the various clinical scoring criteria. Moreover, CECT serves as an anatomic roadmap for guiding radiological and surgical interventions. However, still-controversial experimental studies in animals in the mid-1990s suggested that the use of intravenous radiographic contrast media early in the course of the disease might exacerbate the necrotizing process by further impairing the already compromised pancreatic microcirculation. A series of experimental and clinical studies followed that have both refuted and supported this claim; unfortunately, none is conclusive, and the topic remains, as yet, unresolved.Aims Our objective was to review objectively the available literature found by a Medline search on this subject.Methods Meta-analysis and review.Results and conclusion Our conclusion, after analysis of these studies, is that there are no well-substantiated data that could resolve the controversy. However, several caveats will be offered.     

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。