荧光显微成像对于肝脏微循环的观察及相应肝固有动脉超选灌注动物模型的制作

目的探讨荧光显微成像对于研究肝内微循环的应用价值,总结适用于荧光显微技术的经肝固有动脉超选灌注动物模型的制作方法。方法应用10只Sprague-Dawley大鼠,开腹后,将微导管逆行置于胃十二指肠上动脉(GDA),导管开口朝向肝固有动脉的方向制成肝固有动脉超选灌注动物模型。经微导管分别注入0.02%、0.1%、0.5%、1%荧光素钠0.1ml后,应用荧光显微镜观察肝内微循环的显影情况,评价显影清晰度。经微导管分别注入栓塞剂后(碘油、直径40mm的可降解淀粉微球),观察其引发的微循环变化能否为荧光显微成像显示。结果10只Sprague-Dawley大鼠中,8只成功制成肝固有动脉超选灌注动物模型。荧光显微成像技术可以清晰的显示该动物模型肝内微循环的情况,0.1%的荧光素钠为最佳显影浓度。由栓塞剂引发的直接、间接现象均可为荧光显微成像技术所发现。结论荧光显微成像可以清晰显示肝内微循环结构,对于活体状态下肝脏微循环的形态学研究及栓塞剂的研发有高度的应用价值。适用于该技术的经肝固有动脉超选灌注动物模型的制作方法简单、成功率高,值得推广。     

Noninvasive in vivo analysis of the human hepatic microcirculation using orthogonal polorization spectral imaging

BACKGROUND: Analysis of hepatic microvascular perfusion in humans by direct imaging has been impossible so far. Orthogonal polarization spectral (OPS) imaging represents a new technology that combines simultaneous epi-illumination of the subject with linearly polarized light and noninvasive imaging of the microcirculation by reflectance spectrophotometry. The aim of this study was to evaluate the feasibility of studying the human hepatic microcirculation by OPS imaging in vivo and to define microcirculatory parameters for physiologic conditions. METHODS: The hepatic microcirculation was analyzed in four different regions of both liver lobes in 11 healthy individuals undergoing partial liver resection for living-donor liver transplantation. The optical probe was gently positioned on the liver surface and sequences of at least 20 sec per measurement were recorded by a charge-coupled device camera on videotape. Microhemodynamic parameters were quantified off-line by single-frame and frame-to-frame analysis using a computer-assisted image analysis system. RESULTS: OPS images of the hepatic microcirculation showed an acceptable quality with good resolution. Quantitative analysis revealed a sinusoidal red blood cell velocity of 0.97+/-0.43 mm/sec, a sinusoidal diameter of 8.8+/-0.9 microm, a sinusoidal volumetric blood flow of 58.2+/-9.6 pL/sec, an intersinusoidal distance of 22.6+/-2.5 microm, and a mean functional sinusoidal density of 391+/-30 cm-1. Apart from the sinusoidal red blood cell velocity, all data of the parameters studied matched the pattern of normal distribution. CONCLUSIONS: OPS imaging enabled for the first time direct in vivo visualization and quantification of the human hepatic microcirculation, providing significant insight into microvascular physiology of the human liver, to the extent that these data can be considered to represent physiologic values for human hepatic microcirculation.     

An intravital model to monitor steps of metastatic tumor cell adhesion within the hepatic microcirculation

Organ-specific tumor cell adhesion within the microcirculation of host organs is an important step in the metastatic cascade. Circulating tumor cells have to adhere within the microcirculatory vessels, quickly stabilize their adhesion and probably leave the circulation to avoid toxic effects of hydrodynamic shear forces of circulating blood. Using intravital fluorescence microscopy we established a new model for the intravital observation of colon carcinoma cell adhesion within the hepatic microcirculation. HT-29 (human) and CC531 (rat) colon carcinoma cells were fluorescence labeled using CalceinAM. Single cell suspensions were injected intraarterially in Sprague-Dawley rats. Using intravital fluorescence microscopy adhesive interactions of circulating tumor cells within the hepatic microcirculation were observed at the liver surface. These interactions were analyzed regarding their time course and the localization within the vascular tree. Autofluorescence of liver parenchyma was sufficient for distinction of hepatic sinusoids. Intravital microscopy enabled the differentiation of early events in adhesion formation within hepatic sinosoids, adhesion stabilization, and extravasation of the tumor cells into the liver parenchyma. Tumor cell adhesion occurred almost exclusively within sinusoidal capillaries; however, the diameter of these vessels was usually larger than that of the tumor cells leaving remaining perfused lumen of the capillaries. Colon carcinoma cells rapidly migrated into the liver parenchyma after successful adhesion within the sinusoids. In contrast to common endpoint assays of the metastatic cascade, this in vivo model allows investigations of metastatic colon carcinoma cell adhesion within the liver microcirculation as specific steps during the formation of hematogenous metastasis and their underlying mechanisms. Presented during Digestive Disease Week and the SSAT Residents and Fellow Research Conference, San Francisco, May 2002.     

Graft survival is improved by hepatic denervation before organ harvesting.

BACKGROUND: In a recent study, disturbances of hepatic microcirculation at harvesting caused by in situ organ manipulation dramatically reduced survival after a liver transplant. Because hepatic innervation is involved in the regulation of liver hemodynamics, the effect of denervation before harvesting was assessed here. METHODS: The livers were harvested from female Lewis rats (200-230 g) within 25 min. Briefly, after minimal dissection during the first 12 min, the livers were either manipulated gently or left alone for 13 min. Subsequently, an orthotopic liver transplant was performed after 1 hr of storage in cold UW solution. Some donors livers underwent microsurgical denervation before harvesting or rats were given hexamethonium (10 mg/kg, i.v.), a ganglionic blocking agent. RESULTS: In the nonmanipulated group, survival was 100% after the transplant; however, gentle manipulation decreased survival by about 50%. Furthermore, manipulation elevated serum transaminases and bilirubin 6- to 8-fold 8 hr after the transplant and caused necrosis of about 25% of hepatocytes. After organ harvesting, the rate of entry and exit of fluorescein dextran, a dye confined to the vascular space, was decreased 2- to 4-fold, and the maximal increase of surface fluorescence was blunted about 2-fold. Pimonidazole binding, which reflects tissue hypoxia, was increased 2-fold by manipulation. Denervation of the liver before organ harvesting or treatment with hexamethonium prevented the effects of organ manipulation on all parameters studied. CONCLUSION: These data indicate for the first time that hepatic denervation before organ harvesting prevents detrimental effects of brief, gentle manipulation of the liver during harvesting on survival after the transplant. This is consistent with the hypothesis that organ manipulation disturbs the hepatic microcirculation and causes hypoxia at harvesting using mechanisms dependent on innervation.     

In vivo fluorescence microscopy for quantitative analysis of the hepatic microcirculation in hamsters and rats.

Using intravital fluorescence microscopy and epi-illumination, the hepatic microcirculatory system of Syrian golden hamsters was analyzed, and the morphology and microhemodynamics were compared to those of rats. After contrast enhancement with 1 mumol/kg acridine orange i.v., the epi-illumination technique allows for visualization of capillary sinusoids and postsinusoidal venules, which are running in parallel with the liver surface, while afferent microvessels could be visualized in only few of the liver lobules investigated. In rat livers, the capillary sinusoids showed morphology similar to that of hamsters, however, postsinusoidal venules could frequently not be observed when applying epi-illumination, since these microvessels are piercing perpendicularly into the depth of the liver tissue. Microhemodynamic analysis, including the sinusoidal perfusion rate, sinusoidal red blood cell velocity and diameters, microvascular white blood cell (WBC) count and the phenomenon of WBC-endothelium interaction, as well as the hepatocellular uptake of the fluorescent compound acridine orange were found to be similar in hamsters as compared to rats. Although transillumination for in vivo microscopy may have the potential to visualize the complete hepatic microcirculatory system due to an increased focus depth, the epi-illumination technique has the advantage for quantitative assessment not only of the morphology of the hepatic microcirculatory system and microvascular blood perfusion, but also allows for evaluation of cellular phenomena within the hepatic microvessels, such as WBC accumulation, WBC-endothelium interaction, phagocytotic activity of Kupffer cells, and hepatocellular transport of fluorescent compounds. Hepatic microcircular disturbances, including accumulation of WBCs and WBC-endothelium interaction are causative in the development of organ failure in conditions such as hemorrhagic and septic shock, and, in particular, postischemic reperfusion injury following liver surgery and liver transplantation. Since accumulation of WBCs and their interaction with the microvascular endothelium are primarily found in postsinusoidal venules, in vivo microscopy of the hamster liver represents a favorable model for studies on cellular phenomena within the hepatic microcirculation.     

Laparoscopic organ retrieval for living donor liver transplantation does not prevent graft injury

The cause of transplant failure may be difficult to define. However, organ retrieval before preservation and transplantation is an important factor. Organ manipulation during harvesting, which is inevitable with most techniques, leads to injury upon reperfusion including microcirculatory disturbances. Recently, laparoscopic organ retrieval has been successfully performed for human living donor liver transplantation (LDLT). Pneumoperitoneum for laparoscopy changes the pattern of hepatic blood flow. To study the effects of pneumoperitoneum on the graft prior to cold storage, livers from Sprague-Dawley rats underwent pneumoperitoneum with an intra-abdominal pressure of 8 mm Hg for 90 minutes. Subsequently, intravital microscopy was performed to assess intrahepatic microcirculation and transaminases were measured. Serum transaminases increased 1.5-fold compared with sham controls (P < .05). Intrahepatic microcirculation was significantly disturbed immediately after pneumoperitoneum. If this is confirmed in humans, laparoscopic organ retrieval for LDLT would be expected to decrease graft quality and not be beneficial in liver transplantation.     

A peritoneal cavity chamber for intravital microscopy of the liver under conditions of pneumoperitoneum

BACKGROUND: Intravital microscopy allows direct visualization of the hepatic microvasculature. We report on a novel application of this technique using a chamber model that simulates the conditions of pneumoperitoneum. METHODS: For this purpose, we designed a peritoneal cavity chamber for rats. In the present study, we evaluated the technical procedure without any induction of increased intraabdominal pressure to assess undisturbed hepatic microcirculation. Intravital microscopy of the liver was performed in 12 rats. Animals that underwent the same operative procedure without the chamber served as controls (n = 12). RESULTS: Hepatic sinusoidal perfusion rate, leukocyte-endothelial cell interaction, and bile flow showed no significant differences between the groups. Operating time was longer in the chamber group. CONCLUSION: The peritoneal cavity chamber is an attractive approach for the study of hepatic microvascular, cellular, and molecular mechanisms that are important to our understanding of the potential harmful effects of laparoscopy on hepatic circulation and liver function.     

降钙素基因相关肽对急性肝损伤小鼠肝脏微循环的干预

目的：研究降钙素基因相关肽（CGRP）对刀豆蛋白A（ConA）诱导的小鼠肝损伤模型肝脏微循环的影响。方法：昆明种小鼠60只,随机分为ConA损伤组、CGRP干预组和空白对照组（n=20）,空白对照组注射生理盐水,ConA损伤组用ConA诱导建立小鼠急性肝损伤模型,CGRP干预组在用ConA诱导建模前体外注射CGRP,各组中10只于处理后用激光多普勒血流仪测肝脏的平均血流灌注量,另10只活体观察肝脏微循环流速,最后处死,全部HE染色观察肝脏病理变化。结果：CGRP干预组肝脏的平均血流灌注量和血液流速较ConA损伤组明显增加（P〈0.01）,病理学改变明显减轻。2组的血细胞浓度差异无统计学意义（P〉0.05）。结论：CGRP能够通过改变肝脏组织的灌注影响急性肝损伤时肝脏微循环障碍的程度和病理改变。     

Synergistic effects of brain death and liver steatosis on the hepatic microcirculation

BACKGROUND: The routine transplantation of steatotic livers could potentially mitigate the donor shortage, but so far is associated with a high rate of graft dysfunction. Steatosis and brain death have been perceived as independent risk factors, but they may synergistically target the hepatic microcirculation. This study compares the effects of brain death on the microcirculation of steatotic and normal livers. METHODS: Brain death was induced in obese and lean Zucker rats. Lean and obese sham-operated animals served as controls. Liver microcirculation was investigated using intravital fluorescence microscopy. Serum liver enzyme and reduced glutathione, expression of P-selectin, ICAM-1 and VCAM-1 mRNA in the liver were determined. The ultrastructural alterations were compared by electron microscopy. RESULTS: In nonbrain-dead animals, liver steatosis was associated with smaller sinusoidal diameters, but did not impair sinusoidal perfusion. During brain death, sinusoidal diameter and perfusion were reduced in normal and, to a greater extent, in steatotic livers. Also, more leukocytes were recruited to the microvasculature of steatotic livers than to normal livers in brain-dead state. The highest liver enzyme activities and the lowest hepatic GSH concentrations were measured in brain-dead animals with steatotic livers; only in these organs was endothelial cell swelling regularly observed. In brain-dead state, only the P-selectin mRNA expression was increased in steatotic livers as compared to normal livers. CONCLUSIONS: Brain death amplifies the adverse effects of steatosis on the hepatic microcirculation. Our results underline the need for therapeutic intervention in brain-dead state when steatotic livers are to be used for transplantation.     

Initial hepatic microcirculation correlates with early graft function in human orthotopic liver transplantation.

Microcirculatory disturbances are an initial causative determinant in hepatic ischemia/reperfusion injury. The aim of this study was to assess sinusoidal perfusion during human liver transplantation using orthogonal polarization spectral imaging and to evaluate the significance of intraoperative microcirculation for early postoperative graft function. Hepatic microcirculation was measured in 27 recipients undergoing full-size liver transplantation and compared to a group of 32 healthy living-related liver donors. The microvascular parameters were correlated with postoperative aspartate aminotransferase and bilirubin levels. Hepatic perfusion following liver transplantation was found to be significantly decreased when compared with the control group. Volumetric blood flow within the individual sinusoids increased due to sinusoidal dilatation and enhanced flow velocity. Regression analysis of postoperative aspartate aminotransferase and bilirubin with microvascular parameters revealed significant correlations. The extent of volumetric blood flow increased within the first 30 minutes after reperfusion and showed a significant correlation with postoperative aspartate aminotransferase release and bilirubin elimination. In conclusion, postischemic hepatic microvascular perfusion was analyzed in vivo, demonstrating significant microvascular impairment during liver transplantation. Sinusoidal hyperperfusion appears to confer protection against postischemic liver injury, as given by the correlation with aspartate aminotransferase and bilirubin levels. Thus, these findings may have therapeutic importance with respect to mechanisms mediating postischemic reactive hyperemia.     

Role of cytokines in hepatic ischemia and reperfusion injury]

The liver is an organ with abundant blood flow, consisting of hepatic arterial and portal blood flow. The viability of liver tissue depends on the condition of the hepatic microcirculation which is controlled by hepatic sinusoidal lining cells. Hepatic ischemia and reperfusion (HIR) injury is inevitable in surgical procedures for liver trauma and hepatectomy as well as liver transplantation. Reperfusion through an ischemically damaged organ enhances the tissue injury. Cytokines are pivotal factors in neutrophil-mediated liver injury following HIR, while various other mediators are involved in this insult. Advances in molecular biology have allowed the identification of various cytokines. Inflammatory cytokines such as TNF-alpha are associated with the induction of cellular adhesion molecules and hepatic microcirculatory impairment based on neutrophil-vascular endothelial cell interaction. Members of the chemokine family such as IL-8, CINC, MIP-2, and MCP-1 are involved in neutrophil infiltration in the liver and remote organs. Since each cytokine has a wide variety of actions and interacts' among others' via the cytokine network, their actions in HIR injury have not been determined completely. Kupffer cells have been focused on as a source of cytokine production in HIR injury. Further studies on the mechanisms of cytokine production after HIR and analysis of regulation in the cytokine network would clarify the pathophysiology of HIR injury and the most suitable therapeutic strategy for this insult.     

Microcirculation and excretory function of the liver under conditions of carbon dioxide pneumoperitoneum

Background: To date, the effects of increased abdominal pressure, as given during carbon dioxide (CO₂) pneumoperitoneum, on hepatic microcirculation and biliary excretion are unknown.Methods: Using a custom-made peritoneal cavity chamber, we performed intravital microscopy of the left liver lobe under conditions of CO₂ pneumoperitoneum in a rat model. In addition, biliary excretion was assessed.Results: The establishment of a CO₂ pneumoperitoneum of 4 or 8 mmHg resulted in sinusoidal perfusion failure that was more pronounced in the periportal regions than in the midzonal and pericentral regions of the liver acinus. Biliary excretion was considerably reduced at an intraabdominal pressure of 8 mmHg. Leukocyte–endothelial cell interactions increased significantly in both hepatic sinusoids and postsinusoidal venules.Conclusion: Alterations in hepatic microcirculation and liver function must be taken into consideration in any kind of laparoscopic surgery and may be of particular clinical relevance in patients with liver pathology.     

Prevention of ischemia-reperfusion-induced hepatic microcirculatory disruption by inhibiting stellate cell contraction using rock inhibitor

BACKGROUND: We demonstrated that hepatic stellate cells (HSCs) isolated from rat livers exposed to warm ischemia are significantly contractile when compared with HSCs from intact rat livers. This suggests that ischemia-reperfusion (IR)-induced impairment of sinusoidal microcirculation results, at least in part, from contraction of HSCs. METHODS: Rho-associated coiled-coil forming protein serine/threonine kinase (ROCK) is one of the key regulators of HSCs motility. Therefore we investigated whether Y-27632, a p160ROCK-specific inhibitor, has beneficial effects on warm IR injury in an in vivo rat partial liver IR model and a rat orthotopic liver transplantation model. RESULTS: After reperfusion following 90 min of warm ischemia, livers in untreated control rats had persistent congestion and impaired mitochondrial respiration, as demonstrated by increasing deoxy-hemoglobin and reduced cytochrome oxidase contents in the hepatic tissues using in vivo near-infrared spectroscopy. Serum levels of transaminase and endothelin (ET)-1 in these rats were markedly increased 1 hr after reperfusion. In contrast, when Y-27632 (3-30 mg/kg) was administered orally, hepatic tissue contents of deoxy-hemoglobin and cytochrome oxidase rapidly normalized. In such animals, the elevation of serum transaminase levels, but not that of ET-1 levels, was significantly suppressed. This is consistent with in vitro data demonstrating that Y-27632 causes HSCs to undergo relaxation even in the presence of ET-1. Moreover, in a rat orthotopic liver transplantation model, Y-27632 pretreatment dramatically improved the survival of recipients with liver grafts subjected to 45 min of warm ischemia. CONCLUSIONS: Y-27632 attenuates IR-induced hepatic microcirculation disruption by inhibiting contraction of HSCs.     

Negative impact of systemic catecholamine administration on hepatic blood perfusion after porcine liver transplantation.

Catecholamines are often administered during and after liver transplantation (LTx) to support systemic perfusion and to increase organ oxygen supply. Some vasoactive agents can compromise visceral organ perfusion. We followed the hypothesis that the vasculature of transplanted livers presents with a higher sensitivity, which leads to an increased vulnerability for flow derangement after application of epinephrine (Epi) or norepinephrine (NorEpi). Hepatic macroperfusion and microperfusion during systemic Epi or NorEpi infusion were measured by Doppler flow and thermodiffusion probes in porcine native, denervated, and transplanted livers (n = 16 in each group). Epi or NorEpi were infused (n = 8 in each subgroup) in predefined dosages (low dose = 5 microg/kg/minute and high dose = 10 microg/kg/minute) over 240 minutes. Systemic cardiocirculatory parameters were monitored continuously. Hepatic perfusion data were compared between all groups at comparable time points and dosages. In all native, denervated, and transplanted liver groups, Epi and NorEpi induced an inconsistent rise of mean arterial pressure and heart rate shortly after onset of infusion in both dosages compared with baseline. No significant differences of cardiovascular parameters at comparable time points were observed. In native livers, Epi and NorEpi induced only temporary alterations of hepatic macrocirculation and microcirculation, which returned to baseline 2 hours after onset of infusion. No significant alterations of hepatic blood flow were detected after isolated surgical denervation of the liver. By contrast, transplanted livers showed a progressive decline of hepatic macrocirculation (33-75% reduction) and microcirculation (39-58% reduction) during catecholamine infusions in a dose-dependent fashion. Characteristics of liver blood flow impairment were comparable for both vasoactive agents. In conclusion, pronounced disturbances of hepatic macrocirculation and microcirculation were observed during systemic Epi and NorEpi infusion after LTx compared with native and denervated livers. Microcirculation disturbances after LTx might be explained by impairment of hepatic blood flow regulation caused by an increased sensitivity of hepatic vasculature after ischemia-reperfusion and by lengthening of vasopressor effects caused by reduced hepatocyte metabolism. Clinicians should be aware of this potentially hazardous effect. Therefore, application of catecholamines after clinical LTx should be indicated carefully.     

Changes in hepatic microcirculation and histomorphology in brain-dead organ donors: an experimental study in rats.

OBJECTIVE: To assess the effect of brain death on hormonal homeostasis, hepatic microcirculation, and histomorphology in organ donors. DESIGN: Prospective randomised experimental study. SETTING: Institute for Surgical Research, Germany. SUBJECTS: 12 male Sprague-Dawley rats INTERVENTIONS: 6 rats acted as controls, and 6 had brain death induced by inflation of an intracranial balloon. MAIN OUTCOME MEASURES: Mean arterial pressure, serum concentration of antidiuretic hormone (ADH), thyroxine (T4), free-T4, triiodothyronine (T3) and free-T3, bile production, intravital fluorescence microscopy and electron microscopic appearances. RESULTS: After induction of brain death mean arterial pressure rose within 5 minutes followed by significant hypotension (p < 0.01). ADH concentration was reduced (p < 0.01), as was bile production (p < 0.05). There was impaired sinusoidal perfusion and increased interaction between leucocytes and endothelium in the hepatic microvasculature. The electron microscopic analysis showed vacuolisation of hepatocytes. CONCLUSION: Macrohaemodynamics, ADH homeostasis, and the hepatic microcirculation deteriorate after brain death, which leads to histomorphological damage of hepatocytes and compromised liver function.     

Reduction of hepatic reperfusion injury by antithrombin III and aprotinin

Abstract Disturbance in hepatic microcirculation and leucocyte‐endothelium interaction after warm ischaemia represents one of the leading mechanisms for postoperative organ dysfunction. Recent studies have shown that pretreatment with antithrombin III (AT III) and aprotinin reduces the leucocyte‐endothelium interaction in ischaemic small intestine and during extracorporal circulation in cardiac surgery. Standardized warm hepatic ischaemia and intravital fluorescence videomicroscopy was performed in an experimental study with rats. Animals were pretreated with AT III or aprotinin. Analysis of intravital videomicroscopy showed that the hepatic microcirculation after warm hepatic ischaemia in rats was significantly enhanced by AT III and aprotinin, most likely by reducing the leucocyte‐endothelium interaction. We concluded that drug application before the Pringle manoeuvre might reduce the reperfusion damage after liver resection.     

In vivo evaluation of an implantable portal pump system for augmenting liver perfusion

BACKGROUND: Increasing portal inflow in cirrhosis using a mechanical pump reduces portal venous pressure and improves liver function. A pump has been developed for portal vein implantation in human cirrhosis. This study describes the initial in vivo evaluation in a porcine model. METHODS: Five Large White pigs underwent laparotomy and exposure of the liver. Flow in the hepatic artery, portal vein and hepatic microcirculation was monitored continuously. Hepatic tissue oxygenation was measured by near-infrared spectroscopy. After baseline measurements the pump was inserted into the portal vein. Pump flow rate was then increased stepwise to 50 per cent over the baseline value for a period of 2 h. The pump was then stopped for 20 min and left in situ while continuing to collect systemic and hepatic haemodynamic data. The animal was killed and biopsies for histological examination were taken from the liver, small intestine and spleen. RESULTS: The baseline total hepatic blood flow was 626(39) ml/min; the hepatic artery supplied 18.4(2.1) per cent and the portal vein 81.6(2.1) per cent. The pump was inserted successfully in all animals without surgical complications. During surgical insertion of the pump, the temporary portal vein occlusion resulted in a significant rise in hepatic artery blood flow (22(3) per cent; P < 0.01 versus baseline). Portal vein flow was augmented by pumping; there was a significant correlation between the pump motor speed and portal vein flow (P < 0.0001). This inflow correlated directly with flow in the hepatic microcirculation and hepatic tissue oxygenation (P < 0.001). The pump ran satisfactorily throughout the study. Histological examination revealed no evidence of structural damage to the liver or ischaemic changes in the small intestine or spleen. CONCLUSION: It is technically possible and safe to insert an implantable pump in the portal vein. Portal venous blood flow can be increased up to 50 per cent with a resultant increase in flow in the hepatic microcirculation and hepatic oxygenation and without adverse effects on either hepatic or systemic haemodynamics.     

肝脏缺血后处理的保护作用机制

肝脏缺血后处理是指肝脏在长时间缺血后,在再灌注之前进行一次或数次短暂重复的缺血再灌注,能提高肝脏对长时间缺血的耐受性,减轻缺血再灌注损伤.近几年被证实为一种有效、可控制的新的减轻再灌注损伤的方法.肝脏缺血后处理的保护机制与保护肝窦内皮和肝脏细胞超微结构,减轻活性氧引起的细胞损伤及炎症反应,减轻细胞内及线粒体内钙超载,调控凋亡基因,改变线粒体离子通道开放状态等有关.本文就缺血后处理的机制作一简要综述.     

Hauptdeterminanten der Lebermikrozirkulation im Rahmen systemischer Entzündungsreaktionen

More than 50% of all patients on intensive care units acquire a systemic inflammation such as systemic inflammatory response syndrome (SIRS) or sepsis. The development of hepatic microcirculatory failure with consecutive organ damage might occur during the course of the systemic inflammation. The liver microcirculation is regulated by a complex network of cellular components and specific mediators. The perfusion in liver sinusoids is regulated by the tonus of the contractile Ito cells. Nitric oxide (NO) and carbon monoxide (CO) influence each other and cause the Ito cells to dilate while endothelin results in a contraction of the Ito cells. On-going studies are investigating the role of angiotensin II, catecholamines and prostaglandins for the regulation of the hepatic microcirculatory system during systemic inflammation. Some investigations aim to determine the impact of sedatives and analgesics on the hepatic microcirculation in sepsis and SIRS. Therefore, a decisive recommendation about the choice and dosage of sedatives and analgesics for these patients is not possible. Nevertheless, ketamine, midazolam and fentanyl with their potential anti-inflammatory properties seem to be suitable for patients with systemic inflammation.