Villus tip microcirculation in the rat duodenum

Duodenal microvascular perfusion was measured in anaesthetized rats both as erythrocyte velocity (rev) in capillaries in the tip of duodenal villi and by laser-Doppler flowmetry (LDF). Rev increased transiently by about 40% during the first 5 min of luminal exposure to 10 mM (NaCl to isotonicity) hydrochloric acid, while LDF measurements only showed a transient increase of about 7%, followed by a prolonged reduction by about 11%. Since the LDF signal is a measure not only of villus microcirculation but also of blood flow in the deeper layers, our results may suggest that blood flow is transiently redistributed towards the villi from deeper layers. Hypovolaemia (bleeding by ～ 10% of the blood volume) reduced rev in the capillaries by 63% during the first 5 min of hypotension, but reduced LDF only by about 12%, a discrepancy which suggests a shift in blood flow from the tip to deeper layers. The experiments were performed under atmospheric oxygen tension, but rev in the villus capillaries exposed to abdominal Po₂ (～ 45 mmHg) did not differ significantly from the values obtained under the atmospheric oxygen condition, either in the resting situation or during hypotension. In conclusion, we have developed an animal model in which red cell velocity in the tip of the duodenal villi can be studied for several hours and in which alkaline secretion from the duodenum is similar to previously reported levels. Our results show that the villus tip microcirculation in the duodenum may respond differently from that of deeper layers of the duodenal wall.     

Comparative Analysis of the Response of Microcirculation Parameters and Blood Pressure to Geomagnetic Activity in Healthy People

We analyze the results of daily laser Doppler flowmetry monitoring of blood microcirculation parameters in 9 healthy volunteers performed in 2006-2009. Dependence of microcirculation and BP parameters on geomagnetic activity was analyzed separately in each volunteer (the influence of ambient temperature was previously excluded). Significantly increased parameters of microcirculation in response to higher geomagnetic activity were found in 4 volunteers (44%) and elevated BP in 1 volunteer; in other cases, no reaction was detected. It was shown that individual sensitivity to geomagnetic activity is proportional to its mean level during the period of measurement. Since blood perfusion volume in tissues directly depends on peripheral vascular resistance, we can conclude that under conditions of high geomagnetic activity microvascular tone varies to a greater extent than the tone of major vessels.     

A “Geographic Information Systems” Based Technique for the Study of Microvascular Networks

An automated system (ANET) has been developed to construct interactive maps of microvascular networks, calculate blood flow parameters, and simulate microvascular network blood flow using the geographic information systems (GIS) technology. ANET enables us to automatically collect and display topological, structural, and functional parameters and simulate blood flow in microvascular networks. The user-definable programming interface was used for the manipulation of drawings and data. Visual enhancement techniques such as color can be used to display useful information within a network. In ANET the network map becomes a graphical interface through which network information is stored and retrieved and simulations of microvascular network blood flow are carried out. We have used ANET to study the effects of ionizing radiation on normal tissue microvascular networks. Our results indicate that while vessel diameters significantly increased with age in control animals they decreased in irradiated animals. The tortuosity of irradiated vessels (16.3 ± 1.1 mean±standard error of the mean) was significantly different from control vessels (10.0 ± 1.3) only at 7 days postirradiation. Average red blood cell transit time was significantly different between control (1.6 ± 0.6 s) and irradiated (10.7 ± 5.7 s) microvascular networks at 30 days postirradiation. ANET provides an effective tool for handling the large volume of complex data that is usually obtained in microvascular network studies and for simulating blood flow in microvascular networks. © 1999 Biomedical Engineering Society. PAC99: 8764-t, 8719Tt, 0705Pj, 8750Gi     

Assessing microvascular volume change and filtration from venous hematocrit variation of canine liver and lung

The volume increase of canine liver after 1 min of a 10 mmHg elevation in hepatic venous pressure has been reported as 251 ml/kg tissue. An analysis of the transient hematocrit variation in hepatic venous blood indicated that 16% of the volume change results from transcapillary filtration, 72% from micro-vascular expansion, and 12% from macrovascular expansion. In the analysis, we first used the temporal change of the liver volume to determine the time course of the filtration and microvascular and macrovascular volume change. We next deduced, for a permeable microcirculation with a microvascular hematocrit lower than the feed hematocrit (the Fahraeus effect), how the filtration and microvascular volume change (MVC) produce a hematocrit variation in the blood leaving microcirculation. By accounting for the dispersion of the blood flow, the analysis predicted a hematocrit variation in the hepatic venous blood that matched well with the measured variation over the 1-min course of experiment. A reasonable fit with the hematocrit variation of pulmonary blood also was obtained for experiment with an 8 mm/Hg increase in the arterial and venous pressure perfusing the canine left lower lung lobe. The tissue and vascular volume increase at 1 min was 149 ml/kg tissue with 4% as a result of filtration, 41% as a result of microvascular expansion, and 55% as a result of macrovascular expansion. The large MVCs from the hepatic and pulmonary circulation indicate their microcirculations function as a reservoir in controlling blood volume redistribution.     

Assessing microvascular volume change and filtration from venous hematocrit variation of canine liver and lung

The volume increase of canine liver after 1 min of a 10 mmHg elevation in hepatic venous pressure has been reported as 251 ml/kg tissue. An analysis of the transient hematocrit variation in hepatic venous blood indicated that 16% of the volume change results from transcapillary filtration, 72% from micro-vascular expansion, and 12% from macrovascular expansion. In the analysis, we first used the temporal change of the liver volume to determine the time course of the filtration and microvascular and macrovascular volume change. We next deduced, for a permeable microcirculation with a microvascular hematocrit lower than the feed hematocrit (the Fahraeus effect), how the filtration and microvascular volume change (MVC) produce a hematocrit variation in the blood leaving microcirculation. By accounting for the dispersion of the blood flow, the analysis predicted a hematocrit variation in the hepatic venous blood that matched well with the measured variation over the 1-min course of experiment. A reasonable fit with the hematocrit variation of pulmonary blood also was obtained for experiment with an 8 mm/Hg increase in the arterial and venous pressure perfusing the canine left lower lung lobe. The tissue and vascular volume increase at 1 min was 149 ml/kg tissue with 4% as a result of filtration, 41% as a result of microvascular expansion, and 55% as a result of macrovascular expansion. The large MVCs from the hepatic and pulmonary circulation indicate their microcirculations function as a reservoir in controlling blood volume redistribution.     

Comparison of treatment modalities for hemorrhagic shock

Allogeneic blood resuscitation is the treatment of choice for hemorrhagic shock. When blood is unavailable, plasma expanders, including crystalloids, colloids, and blood substitutes, may be used. Another treatment modality is vasopressin, a vasoconstrictor administered to redistribute blood flow, increase venous return, and maintain adequate cardiac output. While much information exists on systemic function and oxygenation characteristics following treatment with these resuscitants, data on their effects on the microcirculation and correlation of real-time microvascular changes with changes in systemic function and oxygenation in the same animal are lacking. In this study, real-time microvascular changes during hemorrhagic shock treatment were correlated with systemic function and oxygenation changes in a canine hemorrhagic shock model (50-55% total blood loss with a MAP of 45-50 mmHg as a clinical criterion). Following splenectomy and hemorrhage, the dogs were assigned to five resuscitation groups: autologous/shed blood, hemoglobin-based oxygen carrier/Oxyglobin, crystalloid/saline, colloid/Hespan (6% hetastarch), and vasopressin. Systemic function and oxygenation changes were continuously monitored and periodically measured (during various phases of the study) using standard operating room protocols. Computer-assisted intravital video-microscopy was used to objectively analyze and quantify real-time microvascular changes (diameter, red-cell velocity) in the conjunctival microcirculation. Measurements were made during pre-hemorrhagic (baseline), post-hemorrhagic (pre-resuscitation), and post-resuscitation phases of the study. Pre-hemorrhagic microvascular variables were similar in all dogs (venular diameter = 42+/-4 microm, red-cell velocity = 0.55+/-0.5 mm/sec). All dogs showed significant (P < 0.05) post-hemorrhagic microvascular changes: approximately 20% decrease in venular diameter and approximately 30% increase in red-cell velocity, indicative of sympathetic effects arising from substantial blood loss. Microvascular changes correlated with post-hemorrhagic systemic function and oxygenation changes. All resuscitation modalities except vasopressin restored microvascular and systemic function changes close to pre-hemorrhagic values. However, only autologous blood restored oxygenation changes to pre-hemorrhagic levels. Vasopressin treatment resulted in further decreases in venular diameter (approximately 50%) as well as red-cell velocity (approximately 70%) without improving cardiac output. Our results suggested that volume replenishment - not oxygen-carrying capability - played an important role in pre-hospital/en route treatment for hemorrhagic shock. Vasopressin treatment resulted in inadvertent detrimental outcome without the intended benefit.     

Type I interferons contribute to experimental cerebral malaria development in response to sporozoite or blood‐stage Plasmodium berghei ANKA

Cerebral malaria is a severe complication of Plasmodium falciparum infection. Although T‐cell activation and type II IFN‐γ are required for Plasmodium berghei ANKA (PbA)‐induced murine experimental cerebral malaria (ECM), the role of type I IFN‐α/β in ECM development remains unclear. Here, we address the role of the IFN‐α/β pathway in ECM devel‐opment in response to hepatic or blood‐stage PbA infection, using mice deficient for types I or II IFN receptors. While IFN‐γR1^?/? mice were fully resistant, IFNAR1^?/? mice showed delayed and partial protection to ECM after PbA infection. ECM resistance in IFN‐γR1^?/? mice correlated with unaltered cerebral microcirculation and absence of ischemia, while WT and IFNAR1^?/? mice developed distinct microvascular pathologies. ECM resistance appeared to be independent of parasitemia. Instead, key mediators of ECM were attenuated in the absence of IFNAR1, including PbA‐induced brain sequestration of CXCR3⁺‐activated CD8⁺ T cells. This was associated with reduced expression of Granzyme B, IFN‐γ, IL‐12Rβ2, and T‐cell‐attracting chemokines CXCL9 and CXCL10 in IFNAR1^?/? mice, more so in the absence of IFN‐γR1. Therefore, the type I IFN‐α/β receptor pathway contributes to brain T‐cell responses and microvascular pathology, although it is not as essential as IFN‐γ for the development of cerebral malaria upon hepatic or blood‐stage PbA infection.     

冷刺激对青年人甲襞微循环及微区血流量的影响

目的:观察冷刺激对青年人甲襞微循环及微区血流量的影响。方法:应用显微电视录像技术和激光多普勒微循环血流仪,检测33例青年人(包括男12例、女21例)冷刺激后3min甲襞微循环形态、流态和袢周状态以及微区血流量的变化。结果:冷刺激后甲襞微循环由实验前的线流或线粒流变为粒线流或粒流,流速变慢,总积分值增大;微区血流量减少(由5.51±1.18mv减少为5.16±1.38mv,P<0.05)。结论:冷刺激可造成甲襞微循环障碍与甲襞微区血流量减少。     

Effect of Collateral Flow on Catheter-Based Assessment of Cardiac Microvascular Obstruction

Cardiac microvascular obstruction (MVO) associated with acute myocardial infarction (heart attack) is characterized by partial or complete elimination of perfusion in the myocardial microcirculation. A new catheter-based method (CoFI, Controlled Flow Infusion) has recently been developed to diagnose MVO in the catheterization laboratory during acute therapy of the heart attack. A porcine MVO model demonstrates that CoFI can accurately identify the increased hydraulic resistance of the affected microvascular bed. A benchtop microcirculation model was developed and tuned to reproduce in vivo MVO characteristics. The tuned benchtop model was then used to systematically study the effect of different levels of collateral flow. These experiments showed that measurements obtained in the catheter-based method were adversely affected such that collateral flow may be misinterpreted as MVO. Based on further analysis of the measured data, concepts to mitigate the adverse effects were formulated which allow discrimination between collateral flow and MVO.

     

微血管网血流动力学的体外模拟系统

目的 :研究不同微血管网内血流动力学的特点。方法 :自行设计制做的体外循环模拟系统 ,由搏动泵、阻尼器、液容器 (Windkessel腔 )及各种不同口径的弹性管组成。根据不同器官微血管特点 ,用不同口径的弹性管制作了发夹状、树枝状及网囊状的微血管模型。用3个参数 (心率、收缩压Ps/舒张压Pd、动脉血管顺应性C)表示模拟循环系统的动力学状态 ,在此基础上对三种微血管模型在不同的循环压状态下 ,进行了血流动力学模拟研究。结果 :经检验该循环系统在循环回路上模拟的压力及脉动波形基本符合心血管循环的生理特点。当循环压改变时 ,发夹状微血管的第一排管袢内流量和压力的变化较第三排略大 ;当循环压降低时 ,树枝状微血管的终末分支毛细管内压力减少幅度大于初级分支 ,当循环压增高时 ,终末分支毛细管内压力增加幅度小于初级分支 ;网囊状微血管在微循环压降低时其顶端毛细管的压力减少幅度最大。其结果与生理研究相吻合。结论 :本模型在模拟微血管血流动力学方面 ,有较好的仿真性和实用性 ,与活体研究相结合 ,可完善微循环的基础研究。     

Microcirculatory methods for the clinical assessment of hypertension,hypotension, and ischemia

New techniques are now available for studying skin microcirculation non-invasively in humans. The clinically most useful ones are laser Doppler fluxmetry, vital capillaroscopy, dynamic capillaroscopy and fluorescence microscopy. Some of these techniques have now been used in clinical practise for studying the reactivity of the skin microcirculation in patients with hypertension, hypotension and ischemia. It was found that the reactivity to stress in patients with hypertension can be quite different in the skin microvascular bed as compared to the total circulation of the region. In patients with local hypotension due to an arterial obstruction the postocclusive reactive hyperemia response is significantly changed compared to normals. The vasomotion activity is also decreased in the low, pressure area. A marked decrease in the local blood pressure may lead to tissue ischemia. In these patients the risk of skin necrosis can be evaluated by microscopic classification of the structural changes of the capillaries in the area of ischemia. When the skin capillaries are void of erythrocytes the risk of necrosis is imminent.     

Vasomotion in rat diaphragm microcirculation at rest and during stepwise arterial pressure reduction

The effect of haemorrhagic hypotension on the incidence, frequency and relative amplitude of vasomotion in rat diaphragm microcirculation was assessed by laser Doppler flowmetry (LDF). Graded bleeding to four hypotension levels (80, 60, 40 and 30% of the control state) were performed in 24 Sprague–Dawley rats. The incidence of vasomotion was 83% in the control state, 96% at the 80% level, 100% at the 60% level, 96% at the 40% level, and 46% at the 30% level. The median fundamental frequency of vasomotion determined manually during the control state and at the hypotension levels (in descending order) was 4.11 (range, 3.29–5.58) cycles min^?1 (cpm), 4.48 (3.21–5.92) cpm, 4.20 (3.5–5.56) cpm, 4.01 (3.33–5.36) cpm, 3.71 (3.25–4.49) cpm (P < 0.01 from the fundamental frequency at 80 and 60% hypotension levels). The median relative amplitudes determined manually during the control state and descending hypotension levels were 44.5% (range, 24.9–135.9%), 69.4% (26.6–147.2%), 84.0% (40.3–177.1%) (P < 0.01 from resting and last stage of bleeding), 90.40% (26.2–189.6%) (P < 0.01 from resting and last stage of bleeding), 69.2% (35.6–93.2%). We concluded first that during the resting condition, vasomotion was frequently present in diaphragm microcirculation, which is distinct from other vascular beds of skeletal muscles. Second, the relative amplitude of vasomotion during haemorrhagic hypotension plotted against decreasing blood pressure exhibited a reverse U-shaped curve with a maximum at 40–60% of the control blood pressure, while the frequency of vasomotion remained relatively constant until the last stage of haemorrhage and centred around 3–5 cpm.     

64例Ⅱ例糖尿病患者的甲襞微循环改变和加权积分值分析

本文对64例Ⅱ型糖尿病患者和60例正常人进行了甲襞微循环观察。结果提示:Ⅱ型糖尿病患者甲襞微循环在形态、流态,袢周均较正常人有明显异常。并试述应用SWC—ⅡB型微循环参数测量仪和田牛氏甲襞微循环加权积分表的初步体会。     

Evaluation of sublingual microcirculation in children with dengue shock

OBJECTIVE:

To report the sublingual microcirculation observed using Sidestream Dark Field imaging in two children with dengue shock.

METHOD:

Two children, aged 9 and 10 years, were admitted to the pediatric intensive care unit with dengue shock and multiple organ dysfunction. Sublingual microcirculation was assessed in each patient on the first and second days of shock and was assessed a final time when the patients were no longer in shock (on the day prior to extubation) using Sidestream Dark Field technology. The De Backer score and microvascular flow index were used for the analyses.

RESULTS:

Both patients had reduced perfused small vessel density in the first two days and showed predominantly intermittent or no microcirculation flow, as demonstrated by a low microvascular flow index. The blood flow in the large vessels was not affected. Prior to the extubation, the microvascular flow index had increased, although the perfused small vessel density remained diminished, suggesting persistent endothelial dysfunction.

CONCLUSIONS:

Severe microcirculation changes may be involved in the pathophysiological mechanisms that lead to the final stages of dengue shock, which is frequently irreversible and associated with high mortality rates. Microcirculatory monitoring may help elucidate the physiopathology of dengue shock and prove useful as a prognostic tool or therapeutic target.     

The state of the microcirculatory bed,microhemodynamics, and oxygen supply of the liver under conditions of disrupted parasympathetic innervation

Vagotomy is shown to result in disturbances of the microcirculation (a reduced rate of blood flow and distortion of its kinetics), the morphological basis of which consists of certain transformations of the microvascular network organization and ultrastructural changes in the cells lining the sinusoidal capillaries. The most pronounced disorders in microhemodynamics and blood supply of the liver are found 5–14 days after vagotomy. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 118, N ^o 9, pp. 328–330, September, 1994 Presented by V. V. Kupriyanov, Member of the Russian Academy of Medical Sciences     

Laser-Doppler measurements of concentration and velocity of moving blood cells in rat cerebral circulation

In brain cortex all capillaries are perfused with plasma at anyone time while the flow of blood cells is heterogenous. Increased blood flow is associated with increased number of moving erythrocytes in the microcirculation, while capillary recruitment in its classical anatomical sense appears not to exist in the brain. Modulation of the concentration of flowing erythrocytes may influence the oxygen supply to the tissue. Therefore, we examined the possibility that laser-Doppler flowmetry (LDF) could be used to quantify changes in the microvascular concentration of moving blood cells (CMBC) and blood cell velocity (< v >) by comparing LDF measurements with electromagnetic flow measurements in vitro, and confocal laser-scanning microscopy in vivo in the brain of anaesthetized male Wistar rats. In vitro measurements showed that CMBC was affected by changes in haematocrit, while < v > correlated almost linearly with blood cell velocity measured electromagnetically within a relevant physiological range. In vivo studies during hypercapnia (Paco ₂ from 39 ± 4 to 66 ± 5 mmHg) with confocal laser scanning microscopy disclosed a 39 ± 10% increase of cortical capillary erythrocytes, while CMBC measured with LDF increased by 37 ± 5%. Erythrocyte flow velocity in brain cortex capillaries increased by 65 ± 17% with confocal microscopy as compared to 72 ± 8% with LDF. Local electrical stimulation of cerebellar cortex, and application of adenosine or sodium-nitroprusside, increased CMBC and < v > simultaneously, while during hypercapnia the < v > increase preceded the CMBC increase by 30 s. The CMBC rise rapidly reached a steady state in response to all types of stimulation, while < v > continued to increase during the major part, or the entire stimulation period. In conclusion, our data support the hypothesis that LDF may be useful for haemodynamic studies of brain microcirculation.     

Biofeedback regulation of ultrafiltration and dialysate conductivity for the prevention of hypotension during hemodialysis

Intradialytic hypotension remains a frequent complication of dialysis, occurring in up to 33% of patients. We tested a fully integrated biofeedback system (the Hemocontrol system) that monitors and regulates blood volume contraction during hemodialysis. Seven hypotension prone patients were selected for the study. We conducted a prospective crossover study alternating dialysis sessions using the blood volume regulation system and standard dialysis sessions. Event free sessions were defined as dialysis sessions not requiring any therapeutic intervention for hypotension related signs or symptoms. There was a significant improvement in the number of event free sessions with blood volume regulation compared with standard dialysis (50.8% of sessions vs. 29.2%; p < 0.01). Percentages of event free sessions and mean postdialysis systolic blood pressure improved progressively over the course of the study, indicating improved hemodynamic stability over the study period. Therefore, the use of a biofeedback system to monitor and regulate blood volume during dialysis was helpful in restoring cardiovascular stability in a population of hypotension prone hemodialysis patients. Further studies are needed to confirm these preliminary results and to establish the role of blood volume regulation systems in reducing the incidence of hypotension during hemodialysis.     

心肌声学造影在冠状动脉微血管疾病中的临床应用进展

冠状动脉微血管疾病是心肌微循环异常的临床综合征,其出现打破了以往对心脏疾病认识的局限,正引起越来越多的关注。心肌声学造影是评估心肌微循环灌注情况的新技术,有望成为该病的重要检查方法。本文简要综述心肌声学造影的作用机制、冠状动脉微血管疾病的相关概念以及心肌声学造影在冠状动脉微血管疾病的临床诊断、治疗及预后评估方面的作用。     

Vasopressin release during endotoxaemic shock in mice lacking inducible nitric oxide synthase

We tested the hypothesis that nitric oxide (NO) arising from the action of inducible nitric oxide synthase (iNOS) is responsible for the deficiency in vasopressin (AVP) release and consequent hypotension during endotoxaemic shock. Wild-type (WT) and iNOS knockout mice (iNOS^–/–) were given either saline or Escherichia coli lipopolysaccharide (LPS, 1.0 mg/kg i.v., final volume 0.03 ml). Mean arterial blood pressure (MAP) was measured and plasma AVP levels determined before and after LPS or saline injection. In WT mice, MAP was significantly lower 2 h after LPS administration and remained low for the remainder of the 6-h observation period. AVP plasma levels were increased at the 2nd and 4th h of the experiment, returning thereafter to basal levels. Conversely, LPS injection in iNOS iNOS^–/– mice elicited a sustained increase in plasma AVP concentration and attenuated the fall in blood pressure. These data indicate that NO arising from the iNOS plays an important inhibitory role in AVP release during endotoxaemia and may be responsible for the hypotension occurring during this vasodilatory shock.     

Allopurinol inhibits CXC chemokine expression and leukocyte adhesion in endotoxemic liver injury

Objective: Leukocyte activation and recruitment are rate limiting steps in endotoxemic liver injury. We investigated the effect of allopurinol on the expression of CXC chemokines and leukocyte-endothelium interactions, microvascular perfusion failure, and cellular injury and apoptosis in endotoxemic liver injury.Materials and methods: Mice were treated with allopurinol prior to challenge with lipopolysaccharide (LPS) + D-Galactosamine (Gal). Intravital microscopy of the liver microcirculation and analysis of liver enzymes were conducted 6 h later.Results: We observed that allopurinol pre-treatment reduced the number of firmly adherent leukocytes by more than 57% in postsinusoidal venules of endotoxemic mice. Indeed, endotoxin-induced liver injury enzymes were decreased by 76% and sinusoidal perfusion failure was reversed in mice pre-treated with allopurinol. Moreover, administration of allopurinol reduced LPS-induced hepatocyte apoptosis by 56%. Notably, it was found that allopurinol significantly decreased the levels of CXC chemokines (more than 83% reduction) in livers of endotoxemic mice.Conclusions: This study shows that allopurinol markedly protects against endotoxemic liver injury and indicates that reactive oxygen species (ROS) mediate synthesis of CXC chemokines and leukocyte adhesion in the liver in vivo.Received 21 October 2002; returned for revision 26 March 2003; accepted by M. J. Parnham 11 April 2003