Pharmacological interventions targeting the microcirculation following traumatic spinal cord injury

Traumatic spinal cord injury is a devastating disorder chara cterized by sensory,motor,and autonomic dysfunction that seve rely compromises an individual's ability to perform activities of daily living.These adve rse outcomes are closely related to the complex mechanism of spinal cord injury,the limited regenerative capacity of central neurons,and the inhibitory environment fo rmed by traumatic injury.Disruption to the microcirculation is an important pathophysiological mechanism of spinal cord injury.A number of therapeutic agents have been shown to improve the injury environment,mitigate secondary damage,and/or promote regeneration and repair.Among them,the spinal cord microcirculation has become an important target for the treatment of spinal cord injury.Drug inte rventions targeting the microcirculation can improve the microenvironment and promote recovery following spinal cord injury.These drugs target the structure and function of the spinal cord microcirculation and are essential for maintaining the normal function of spinal neuro ns,axons,and glial cells.This review discusses the pathophysiological role of spinal cord microcirculation in spinal cord injury,including its structure and histopathological changes.Further,it summarizes the progress of drug therapies targeting the spinal cord mic rocirc ulation after spinal cord injury.

Xuebijing improves intestinal microcirculation dysfunction in septic rats by regulating the VEGF-A/PI3K/Akt signaling pathway

BACKGROUND:This study aims to explore whether Xuebijing(XBJ) can improve intestinal microcirculation dysfunction in sepsis and its mechanism.METHODS:A rat model of sepsis was established by cecal ligation and puncture(CLP).A total of 30 male SD rats were divided into four groups:sham group,CLP group,XBJ + axitinib group,and XBJ group.XBJ was intraperitoneally injected 2 h before CLP.Hemodynamic data(blood pressure and heart rate) were recorded.The intestinal microcirculation data of the rats were analyzed via microcirculation imaging.Enzyme-linked immunosorbent assay(ELISA) kits were used to detect the serum levels of interleukin-6(IL-6),C-reactive protein(CRP),and tumor necrosis factor-α(TNF-α) in the rats.Histological analysis and transmission electron microscopy were used to analyze the injury of small intestinal microvascular endothelial cells and small intestinal mucosa in rats.The expression of vascular endothelial growth factor A(VEGF-A),phosphoinositide 3-kinase(PI3K),phosphorylated PI3K(p-PI3K),protein kinase B(Akt),and phosphorylated Akt(p-Akt) in the small intestine was analyzed via Western blotting.RESULTS:XBJ improved intestinal microcirculation dysfunction in septic rats,alleviated the injury of small intestinal microvascular endothelial cells and small intestinal mucosa,and reduced the systemic inflammatory response.Moreover,XBJ upregulated the expression of VEGF-A,p-PI3K/total PI3K,and p-Akt/total Akt in the rat small intestine.CONCLUSION:XBJ may improve intestinal microcirculation dysfunction in septic rats possibly through the VEGF-A/PI3K/Akt signaling pathway.

In vivo pilot study into superficial microcirculatory characteristics of colorectal adenomas using novel high-resolution magnifying endoscopy with blue laser imaging

BACKGROUND No studies have yet been conducted on changes in microcirculatory hemody-namics of colorectal adenomas in vivo under endoscopy.The microcirculation of the colorectal adenoma could be observed in vivo by a novel high-resolution magnification endoscopy with blue laser imaging(BLI),thus providing a new insight into the microcirculation of early colon tumors.AIM To observe the superficial microcirculation of colorectal adenomas using the novel magnifying colonoscope with BLI and quantitatively analyzed the changes in hemodynamic parameters.METHODS From October 2019 to January 2020,11 patients were screened for colon adenomas with the novel high-resolution magnification endoscope with BLI.Video images were recorded and processed with Adobe Premiere,Adobe Photoshop and Image-pro Plus software.Four microcirculation parameters:Microcirculation vessel density(MVD),mean vessel width(MVW)with width standard deviation(WSD),and blood flow velocity(BFV),were calculated for adenomas and the surrounding normal mucosa.RESULTS A total of 16 adenomas were identified.Compared with the normal surrounding mucosa,the superficial vessel density in the adenomas was decreased(MVD:0.95±0.18 vs 1.17±0.28μm/μm2,P<0.05).MVW(5.11±1.19 vs 4.16±0.76μm,P<0.05)and WSD(11.94±3.44 vs 9.04±3.74,P<0.05)were both increased.BFV slowed in the adenomas(709.74±213.28 vs 1256.51±383.31μm/s,P<0.05).CONCLUSION The novel high-resolution magnification endoscope with BLI can be used for in vivo study of adenoma superficial microcirculation.Superficial vessel density was decreased,more irregular,with slower blood flow.

Retinal microcirculation changes in prediabetic patients with shortterm increased blood glucose using optical coherence tomography angiography

BACKGROUND Retinal microcirculation alterations are early indicators of diabetic microvascular complications.Optical coherence tomography angiography(OCTA)is a noninvasive method to assess these changes.This study analyzes changes in retinal microcirculation in prediabetic patients during short-term increases in blood glucose using OCTA.AIM To investigate the changes in retinal microcirculation in prediabetic patients experiencing short-term increases in blood glucose levels using OCTA.METHODS Fifty volunteers were divided into three groups:Group 1[impaired fasting glucose(IFG)or impaired glucose tolerance(IGT)],Group 2(both IFG and IGT),and a control group.Retinal microcirculation parameters,including vessel density(VD),perfusion density(PD),and foveal avascular zone(FAZ)metrics,were measured using OCTA.Correlations between these parameters and blood glucose levels were analyzed in both the fasting and postprandial states.RESULTS One hour after glucose intake,the central VD(P=0.023),central PD(P=0.026),and parafoveal PD(P<0.001)were significantly greater in the control group than in the fasting group.In Group 1,parafoveal PD(P<0.001)and FAZ circularity(P=0.023)also increased one hour after glucose intake.However,no significant changes were observed in the retinal microcirculation parameters of Group 2 before or after glucose intake(P>0.05).Compared with the control group,Group 1 had a larger FAZ area(P=0.032)and perimeter(P=0.018),whereas Group 2 had no significant differences in retinal microcirculation parameters compared with the control group(P>0.05).Compared with Group 1,Group 2 had greater central VD(P=0.013)and PD(P=0.008)and a smaller FAZ area(P=0.012)and perimeter(P=0.010).One hour after glucose intake,Group 1 had a larger FAZ area(P=0.044)and perimeter(P=0.038)than did the control group,whereas Group 2 showed no significant differences in retinal microcirculation parameters compared with the control group(P>0.05).Group 2 had greater central VD(P=0.042)and PD(P=0.022)and a smaller FAZ area(P=0.015)and perimeter(P=0.016)than Group 1.At fasting,central PD was significantly positively correlated with blood glucose levels(P=0.044),whereas no significant correlations were found between blood glucose levels and OCTA parameters one hour after glucose intake.CONCLUSION A short-term increase in blood glucose has a more pronounced effect on retinal microcirculation in prediabetic patients with either IFG or IGT.

突发性聋的治疗困惑与思考

突发性聋近年来发病呈明显上升趋势,并呈现出发病年轻化的特点,业已引起耳科临床医师关注。突发性聋发病突然,对患者心理和生活质量的影响不可忽视,以临床急症处理的理念也逐渐得到大家的认同。由于国内外医疗体制的差异,国外突发性聋的治疗规范与国内差异较大,实用性不强。而近年来国内突发性聋方面的研究也层出不穷,多家国内大型医院合作的多中心研究也获得可喜研究结果,并制定突发性聋的中国治疗规范。

冠心病患者的甲襞微循环改变

本文对30例冠心病患者进行了甲襞微循环观察,同时以30例健康人作为对照,应用田牛甲襞微循环加权积分法,进行了综合分析。结果表明:疾病组加权积分值均高于对照组(P【0.01),微循环轻度至中度异常,尤以管袢畸型、血流缓慢、红细胞中度聚集以及渗出显著。现报告如下:

肾综合征出血热甲皱微循环加权积分值临床分析

From 1985 to 1987 Nailfold microcirculation was detected in 60 cases of HFRS for 164 times, and were comprehen- sively evaluated. The results showed that the changes of the capillary loop form were the main feature in febrile phase, ∑(A×B) was 3. 15. The capillary loop form, fluidity and the condition around the loops all changed obviously in hypotensive phase ∑(A×B)was 5. 49. The capillary loop form and the condition around the loops also changed obviously ,∑ (A×B) was 4. 73. The fluidity of blood, however, was improved. ,The microcirculation in most of the patients in diuresis phase had recorded, except severe and fatal cases, ∑(A×B) was 3. 83. Analysing ∑(A×B), we considered that there were striking differences among mild, moderate and severe cases (P<0. 05). There was no striking differences between severe and fatal cases(P>0. 05). Nailfold microcirculation can reflect the human body microcirculation function in a certain de- gree. The clinical significances detecting it are: (1) It may be regarded as a reference item for early diagnosis and for determing a degree when the patients are admitted, (2)It may be a supervise measure in hypotensive phase, (3)It may be a reference item for supervising DIC and for anticoagulant treatment. (4) The dynamic changes of nailfold microcirculation may be a reference item for conjecturing prognosis, The quantitative analysis of nailfold microcirculation by∑ (A× B) can reflect 15 items for the changes of human body microcirculation. It can provide the reliable information for guiding the treat -ment arid conjecturing prognosis in HFRS,

多功能生化纤维内衣对微循环的影响

<正>近2年国内研制成功的多功能生化纤维已通过国家科委和纺织部的鉴定,并取得了中国专利。目前已制成系列保健用品。为探讨该生化纤维制品对微循环的影响,我们使用该生化纤维制成的内衣进行临床微循环测试。现报告如下。

Effects of different resuscitation fluid on severe acute pancreatitis

AIM: To compare effects of different resuscitation fluid on microcirculation, inflammation, intestinal barrier and clinical results in severe acute pancreatitis (SAP). METHODS: One hundred and twenty patients with SAP were enrolled at the Pancreatic Disease Institute between January 2007 and March 2010. The patients were randomly treated with normal saline (NS group), combination of normal saline and hydroxyethyl starch (HES) (SH group), combination of normal saline, hydroxyethyl starch and glutamine (SHG group) in resuscitation. The ratio of normal saline to HES in the SH and SHG groups was 3:1. The glutamine (20% glutamine dipeptide, 100 mL/d) was supplemented into the resuscitation liquid in the SHG group. Complications and outcomes including respiratory and abdominal infection, sepsis, abdominal hemorrhage, intra-abdominal hypertension, abdominal compartment syndrome (ACS), renal failure, acute respiratory distress syndrome (ARDS), multiple organ dysfunction syndrome (MODS), operation intervention, length of intensive care unit stay, length of hospital stay, and mortality at 60 d were compared. Moreover, blood oxygen saturation (SpO 2 ), gastric intramucosal pH value (pHi), intra-abdominal pressure (IAP), inflammation cytokines, urine lactulose/mannitol (L/M) ratio, and serum endotoxin were investigated to evaluate the inflammatory reaction and gut barrier. RESULTS: Compared to the NS group, patients in the SH and SHG groups accessed the endpoint more quickly (3.9 ± 0.23 d and 4.1 ± 0.21 d vs 5.8 ± 0.25 d, P < 0.05) with less fluid volume (67.26 ± 28.53 mL/kg/d, 61.79 ± 27.61 mL/kg per day vs 85.23 ± 21.27 mL/kg per day, P < 0.05). Compared to the NS group, incidence of renal dysfunction, ARDS, MODS and ACS in the SH and SHG groups was obviously lower. Furthermore, incidence of respiratory and abdominal infection was significantly decreased in the SH and SHG groups, while no significant difference in sepsis was seen. Moreover, less operation time was needed in the SH and SHG group than the NS group, but the difference was not significant. The mortality did not differ significantly among these groups. Blood SpO 2 and gastric mucosal pHi in the SH and SHG groups increased more quickly than in the NS group, while IAP was significantly decreased in the SH and SHG group. Moreover, the serum tumor necrosis factor-α, interleukin-8 and C-reactive protein levels in the SH and SHG groups were obviously lower than in the NS group at each time point. Furthermore, urine L/M ratio and serum endotoxin were significantly lower in the SH group and further decreased in the SHG group.CONCLUSION: Results indicated that combination of normal saline, HES and glutamine are more efficient in resuscitation of SAP by relieving inflammation and sustaining the intestinal barrier.

Review:Mechanism of acute pancreatitis complicated with injury of intestinal mucosa barrier

Acute pancreatitis (AP) is a common acute abdomen in clinic with a rapid onset and dangerous pathogenetic condition. AP can cause an injury of intestinal mucosa barrier, leading to translocation of bacteria or endotoxin through multiple routes, bacterial translocation (BT), gutorigin endotoxaemia, and secondary infection of pancreatic tissue, and then cause systemic in- flammatory response syndrome (SIRS) or multiple organ dysfunction syndrome (MODS), which are important factors influencing AP’s severity and mortality. Meanwhile, the injury of intestinal mucosa barrier plays a key role in AP’s process. Therefore, it is clinically important to study the relationship between the injury of intestinal mucosa barrier and AP. In addition, many factors such as microcirculation disturbance, ischemical reperfusion injury, excessive release of inflammatory mediators and apoptosis may also play important roles in the damage of intestinal mucosa barrier. In this review, we summarize studies on mechanisms of AP.

Inflammatory mediators and microcirculatory disturbance in acute pancreatitis

BACKGROUND: Inflammatory mediators are not only initiation factors of acute pancreatitis (AP) but also key factors causing pancreatic hemorrhage and necrosis, which damage important organs such as the heart, brain, liver, kidney and lung. Microcirculatory disturbance in AP has attracted widespread attention. In order to provide a theoretical basis for clinical therapy of AP, it is very important to explore the effect of inflammatory mediators on microcirculatory disturbance in this disease. DATA SOURCES: In this review, the impact of inflammatory mediators on microcirculatory disturbance in AP was reviewed according to the literature, especially the articles indexed in PubMed and books published in China and reports from websites. RESULTS: At present, inflammatory mediation and microcirculatory disturbance are the two major hypotheses to explain the development of AP. Although experimental studies have shown that inflammatory mediators induce or aggravate microcirculatory disturbance, the clinical application of these findings is still difficult because the inflammatory mediators are diverse and their research is not comprehensive and thorough. CONCLUSION: It is very important to explore the influence of inflammatory mediators on microcirculatory disturbance in AP.

Effects of Aloe vera and sucralfate on gastric microcirculatory changes,cytokine levels and gastric ulcer healing in rats

AIM： To compare the effects of Aloe vera and sucralfate on gastric microcirculatory changes, cytokine levels and gastric ulcer healing. METHODS： Male Spraque-Dawley rats （n=48） were divided into four groups. Group 1 served as control group, group 2 as gastric ulcer group without treatment, groups 3 and 4 as gastric ulcer treatment groups with sucralfate and Aloe vera. The rats from each group were divided into 2 subgroups for study of leukocyte adherence, TNF-α and IL-10 levels and gastric ulcer healing on days 1 and 8 after induction of gastric ulcer by 20% acetic acid. RESULTS： On day 1 after induction of gastric ulcer, the leukocyte adherence in postcapillary venule was significantly （P〈 0.05） increased in the ulcer groups when compared to the control group. The level of TNF-α was elevated and the level of IL-10 was reduced. In the ulcer groups treated with sucralfate and Aloe vera, leukocyte adherence was reduced in postcapillary venule. The level of IL-10 was elevated, but the level of TNF-a had no significant difference. On day 8, the leukocyte adherence in postcapillary venule and the level of TNF-α were still increased and the level of IL-10 was reduced in the ulcer group without treatment. The ulcer treated with sucralfate and Aloe vera had lower leukocyte adherence in postcapillary venule and TNF-α level. The level of IL-10 was still elevated compared to the ulcer group without treatment. Furthermore, histopathological examination of stomach on days 1 and 8 after induction of gastric ulcer showed that gastric tissue was damaged with inflammation. In the ulcer groups treated with sucralfate and Aloe vera on days 1 and 8, gastric inflammation was reduced, epithelial cell proliferation was enhanced and gastric glands became elongated. The ulcer sizes were also reduced compared to the ulcer group without treatment. CONCLUSION： Administration of 20% acetic acid can induce gastric inflammation, increase leukocyte adherence in postcapillary venule and TNF-α level and reduce IL-10 level. Aloe vera treatment can reduce leukocyte adherence and TNF-αlevel, elevate IL-10 level and promote gastric ulcer healing.

Plasma endothelin and nitric oxide levels in patients with acute pancreatitis

Objective: To explore the changes of plasma endothelin(ET) and nitric oxide (NO) levels in patients with a-cute pancreatitis.Methods: The level of plasma ET was measured by ra-dioactive-immunoassay, and NO by spectrophotometry.Results: The levels of ET, NO and the ET/NO ratioin patients with severe acute pancreatitis(SAP) within24 hours in hospital were all significantly higher thanthose in other groups of patients [(176±8)pg/ml,(97±11) μmol/L, and 1.83±0.12, P<0.01]. Com-pared to healthy controls(N), the levels of ET and NOin patients without pancreatitis acute abdomen (NAP)and patients with mild acute pancreatitis (MAP) in-creased significantly (P<0.01). After appropriate treat-ment, the levels of ET and NO in the MAP groupwere lower (P<0.01). Compared with those beforetreatment, the levels of ET and NO in the SAP groupon the 3rd and 7th day in hospital dropped signifi-cantly(P<0.01).The ET/NO ratio on the 7th daywas also lower than that on admission (P<0.01).Conclusions: The malfunction of endothelial cells andthe increased ET/NO ratio may be related to the mecha-nism of pancreatic microcirculatory disturbance in pa-tients with SAP; early dynamic determination of theseparameters may help predict the prognosis of SAP.

Influence of splanchnic vascular infusion on the content of endotoxins in plasma and the translocation of intestinal bacteria in rats with acute hemorrhage necrosis pancreatitis

The main reason for the death of the patient with acute hemorrhage necrosis pancreatitis (AHNP) is pancreatic infection and multi-organ failure caused by endotoxemia and intestinal bacterial translocation[1-7]. However, the pathogenesis of endotoxemia and intestinal bacterial translocation remains a question[8-10]; moreover, no effective method of prevention and cure for it has been found till now[11 -15] In the present study, we infused low dose dopamine and low molecular weight dextran through the catheters to abdominal aorta and portal vein, and observed its influence on the endotoxin concentration in plasma and the rate of translocation of intestinal bacteria in AHNP rats.

Intestinal microcirculation dysfunction in sepsis: pathophysiology, clinical monitoring, and therapeutic interventions

BACKGROUND:Intestinal microcirculation dysfunction is an important factor that causes poor prognosis in sepsis patients and is an important pathophysiological basis for the occurrence and development of sepsis.DATA RESOURCES:PubMed,Web of Science,and China National Knowledge Infrastructure(CNKI)were searched from inception to August 1,2021.The search was limited to the English language only.Two reviewers independently identified studies related to intestinal microcirculation dysfunction in sepsis.Exclusion criteria were duplicate articles according to multiple search criteria.RESULTS:Fifty articles were included,and most of them were animal studies.These studies reported pathogenesis,including endothelial dysfunction,leukocyte recruitment and adhesion,microthrombus formation,microcirculation hypoperfusion,and redistribution of intestinal wall blood flow.The monitoring methods of intestinal microcirculation were also diverse,including handheld microscopes,intravital microscopy(IVM),laser Doppler blood flow instruments,laser speckle contrast imaging,tissue refl ectance spectrophotometry,biochemical markers of intestinal ischemia,and histopathological examination.In view of the related pathogenesis of intestinal microcirculation disorder in sepsis,existing studies also have diff erent opinions on its treatment.CONCLUSIONS:Limited by monitoring,there are few clinical studies on intestinal microcirculation dysfunction in sepsis.Related research mainly focuses on basic research,but some progress has also been made.Therefore,this review may provide a reference for future research on intestinal microcirculation dysfunction in sepsis.

Changes of gastric and intestinal blood flow, serum phospholipase A_2 and interleukin-1β in rats with acute necrotizing pancreatitis

AIM:To explore the relationship between gastric and intestinal microcirculatory impairment and inflammatory mediators released in rats with acute necrotizing pancreatitis (ANP). METHODS: A total of 64 rats were randomized into control group and ANP group. ANP model was induced by injection of 5% sodium taurocholate under the pancreatic membrane. Radioactive biomicrosphere technique was used to measure the gastric and intestinal tissue blood flow at 2 and 12 h after the induction of ANP, meanwhile serum phospholipase A2 (PLA2) activities and interleukin-1β levels were determined. Pathologic changes in pancreas, gastric and intestinal mucosae were studied. RESULTS: The gastric blood flow in ANP group (0.62±0.06 and 0.35±0.05) mL/(min·g) was significantly lower than that in control group (0.86±0.11 and 0.85±0.06) mL/(min·g) (P<0.01) at 2 and 12 h after induction of ANP. The intestinal blood flow in ANP group (0.80±0.07 and 0.50±0.06) mlV(min·g) was significantly lower than that in control group (1.56±0.18 and 1.61±0.11) mL/(min·g) (P<0.01). Serum PLA2 activities (94.29±9.96 and 103.71± 14.40) U/L and IL-1β levels (0.78±0.13 and 0.83±0.20)μg/L in ANP group were higher than those in control group (65.27±10.52 and 66.63±9.81) U/L, (0.32±0.06 and 0.33±0.07)μg/L (P<0.01). At 2 and 12 h after introduction of the model, typical pathologic changes were found in ANP. Compared with control group, the gastric and intestinal mucosal pathologic changes were aggravated significantly (P<0.01) at 12 h after induction of ANP. Gastric and intestinal mucosal necrosis, multiple ulcer and hemorrhage occurred. CONCLUSION: Decrease of gastric and intestinal blood flow and increase of inflammatory mediators occur simultaneously early in ANP, both of them are important pathogenic factors for gastric and intestinal mucosal injury in ANP.

Preventive effect of tetramethylpyrazine on intestinal mucosal injury in rats with acute necrotizing pancreatitis

AIM： To evaluate the role of microcirculatory disorder （MCD） and the therapeutic effectiveness ;of tetramethylpyrazine （TMP） on intestinal mucosa injury in rats with acute necrotizing pancreatitis （ANP）.METHODS： A total of 192 Sprague-Dawley rats were randomly divided into three groups： normal control group （C group）, ANP group not treated with TMP （P group）, ANP group treated with TMP （T group）. An ANP model was induced by injection of 50 g/L sodium taurocholate under the pancreatic membrane （4 mL/kg）. C group received isovolumetric injection of 9 g/L physiological saline solution using the same method. T group received injection of TMP （10 mL/kg） via portal vein. Radioactive biomicrosphere technique was used to measure the blood flow at 0.5, 2, 6 and 12 h after the induction of ANP. Samples of pancreas, distal ileum were collected to observe pathological changes using a validated histology score. Intestinal tissues were also used for examination of myeloperoxidase （MPO） expressed intraceUularly in azurophilic granules of neutrophils.RESULTS： The blood flow was significantly lower in P group than in C group （P 〈 0.01）. The pathological changes were aggravated significantly in P group. The longer the time, the severer the pathological changes. The intestinal MPO activities were significantly higher in P group than in C group （P 〈 0.01）. The blood flow of intestine was significantly higher in T group than in P group after 2 h （P 〈 0.01）. The pathological changes were alleviated significantly in T group. MPO activities were significantly lower in T group than in P group （P 〈 0.01 or P 〈 0.05）. There was a negative correlation between intestinal blood flow and MPO activity （r = -0.981, P 〈 0.01） as well as between intestinal blood flow and pathologic scores （r = -0.922, P 〈 0.05）.CONCLUSION： MCD is an important factor for intestinal injury in ANP. TMP can ameliorate the condition of MCD and the damage to pancreas and intestine.

Epidural anaesthesia restores pancreatic microcirculation and decreases the severity of acute pancreatitis

AIM： To investigate the effect of epidural anaesthesia （EA） on pancreatic microcirculation during acute pancreatitis （AP）. METHODS： AP was induced by injection of sodium taurocholate into the pancreatic duct of Sprague-Dawley rats. To realize EA, a catheter was introduced into the epidural space between T7 and T9 and bupivacaine was injected. Microcirculatory flow was measured by laser Doppler flowmetry. Arterial blood gas analyses were performed. At the end of the experiment （≤ 5 h）, pancreas was removed for histology. The animals were divided into three groups： Group 1 （n =9）, AP without EA, Group 2 （n = 4）, EA without AP; and Group 3 （n = 6）, AP treated by EA. RESULTS： In Group 1, pancreatic microcirculatory flow prior to AP was 1414, 39 perfusion units （PU）. After AP, microcirculatory flow obviously decreased to 9 4-6 PU （P〈0.05）. Metabolic acidosis developed with base excess （BE） of - 14 4, 3 mmol/L. Histology revealed extensive edema and tissue necrosis. In Group 2, EA did not significantly modify microcirculatory flow. BE remained unchanged and histological analysis showed normal pancreatic tissue. In Group 3, AP initially caused a significant decrease in microcirculatory flow from 155 ± 25 to 11± 7 PU （P〈0.05）. After initiation of EA, microcirculatory flow obviously increased again to 81±31 PU （P〈0.05）. BE was -6±4 retool/L, which was significantly different compared to Group 1 （P〈0.05）. Furthermore, histology revealed less extensive edema and necrosis in pancreatic tissue in Group 3 than that in Group 1. CONCLUSION： AP caused dramatic microcirculatory changes within the pancreas, with development of metabolic acidosis and tissue necrosis. EA allowed partial restoration of microcirculatory flow and prevented development of tissue necrosis and systemic complications. Therefore, EA should be considered as therapeutic option to prevent evolution from edematous to necrotic AP.

Coronary microvascular dysfunction in diabetes mellitus:A review

The exploration of coronary microcirculatory dysfunction in diabetes has accelerated in recent years.Cardiac function is compromised in diabetes.Diabetic patients manifest accelerated atherosclerosis in coronary arteries.These data are confirmed in diabetic animal mod-els,where lesions of small coronary arteries have been described.These concepts are epitomized in the classic microvascular complications of diabetes,i.e.blindness,kidney failure and distal dry gangrene.Most importantly,accumulating data indicate that insights gained from the link between inflammation and diabetes can yield predictive and prognostic information of considerable clinical utility.This review summarizes the evidence for the predisposing factors and the mechanisms involved in diabetes,and assesses the current state of knowledge regarding the triggers for inflammation in this disease.We evaluate the roles of hyperglycemia,oxidative stress,polyol pathway,protein kinase C,advanced glycation end products,insulin resistance,peroxisome proliferator-activated receptor-γ,inflammation,and diabetic cardiomyopathy as a "stem cell disease".Furthermore,we discuss the mechanisms responsible for impaired coronary arteriole function.Finally,we consider how new insights in diabetes may provide innovative therapeutic strategies.

Heparin improves organ microcirculatory disturbances in caerulein-induced acute pancreatitis in rats

AIM:Microcirculatory disturbances are important early pathophysiological events in various organs during acute pancreatitis.The aim of the study was to evaluate changes in microperfusion of the pancreas,liver,kidney,stomach, colon,skeletal muscle,and to investigate the influence of heparin on the organ microcirculation in caerulein-induced experimental acute pancreatitis. METHODS:Acute pancreatitis was induced by 4 intraperitoneal injections of caerulein(Cn)(15 μg/kg).The organ microcirculation was measured by laser Doppler flowmetry.Serum interleukin 6 and hematocrit levels were analysed. RESULTS:Acute pancreatitis resulted in a significant drop of microperfusion in all examined organs.Heparin administration(2×2.5 mg/kg)improved the microcirculation in pancreas(36.9±4% vs 75.9±10%),liver(56.6±6% vs 75.2±16%),kidney (45.1±6% vs 79.3±5%),stomach (65.2±8% vs 78.1±19%),colon(69.8±6% vs 102.5±19%), and skeletal muscle (59.2±6% vs 77.9±13%).Heparin treatment lowered IL-6(359.0±66 U/mL vs 288.5±58 U/mL) and hematocrit level(53±4% vs 46±3%). CONCLUSION:Heparin administration has a positive influence on organ microcirculatory disturbances accompanying experimental Cn-induced acute pancreatitis.