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[Liver microcirculative disturbance in schistosomiasis portal hypertension].

Using reing resin vascular casts, ink perfusion, VG and electron microscope. We studied the liver microcirculative disturbance in rabbits (n = 20) and mice (n = 10) with chronic schistosomiasis. The results showed a decrease in the liver sinusoid number, tortuosity of the terminal branches of the portal vein, formation of a basement membrane in the space of Disse, capillarization of the sinusoid. These results suggest that liver microcirculative disturbance can contribute to schistosomiasis portal hypertension.

Animals↗

Microcirculation of nailfold capillaries in chronic hemodialysis patients with and without diabetes mellitus.

The present study was intended to determine whether hemodialysis patients with arteriovenous fistula showed changes of microcirculation in the upper extremity. In addition, the study was to show whether such changes were correlated to the shunt parameters, such as the shunt flow volume, and whether the presence of diabetes mellitus had any additional influence. The study included 43 patients undergoing chronic hemodialysis; ten of the 43 patients were diabetics. Morphological and hemodynamic parameters of microcirculation were determined using quantitative capillaroscopy, flow volume in the brachial artery and shunt flow were measured by means of pulsed Doppler ultrasonography. While the morphological microcirculatory parameters did not show any differences between shunt arm and contralateral side, statistically significant differences were seen for resting blood cell velocity and for the time to peak capillary blood cell velocity after reactive hyperemia. For the latter a correlation to the shunt flow volume could also be demonstrated for nondiabetic patients. As expected, the time to peak blood cell velocity after reactive hyperemia was prolonged in both arms of patients with diabetes mellitus. Apparently, diabetes mellitus had a more pronounced effect on hemodynamic parameters than the Cimino shunt. This and the shunt flow will result in a Raynaud symptomatology. Other symptoms associated with chronic hemodialysis are mainly related to the duration of hemodialysis.

Arm↗

Improvement of impaired pancreatic microcirculation by isovolemic hemodilution protects pancreatic morphology in acute biliary pancreatitis.

Impairment of the pancreatic microcirculation is a characteristic finding in experimental biliary pancreatitis. Isovolemic hemodilution with dextran 60 has been proven to maintain pancreatic capillary perfusion. To evaluate the significance of this therapeutic approach with respect to histologic changes, intravital microscopic assessment of the microcirculation was combined with a morphometric analysis of the pancreas by means of light microscopy in rabbits (n = 18). Pancreatic capillary perfusion was maintained in the rabbits subjected to hemodilution 30 minutes after the induction of pancreatitis with 54 percent of the capillaries still being perfused at 12 hours, compared with only 16 percent in the control group. The improved capillary perfusion resulted in a significant reduction of those changes considered potentially reversible (cell vacuolization and interstitial edema) that surround zones of necrosis. However, because of the early establishment of necrosis in this model, hemodilution was unsuccessful in preventing all cell death. Hemodilution can limit the progressive extension of pancreatic injury in this model of biliary pancreatitis.

Acute Disease↗

Effect of heparin on thrombin inhibition in the microcirculation.

Disappearance of thrombin enzymatic activity was measured during recirculation through the microvasculature in a rat Langendorff heart preparation. This resulted in a 50% loss of thrombin from the recirculating solution. No increased loss of thrombin could be demonstrated if a mixture of antithrombin III and thrombin was recirculated, compared to thrombin alone. If, however, a heparin/thrombin mixture was recirculated, a 90% loss of thrombin could be demonstrated. Pretreating the microvasculature with large amounts of heparin resulted in recovery of antithrombin III in the recirculated heparin solution. At a subsequent recirculation with a heparin/thrombin mixture the loss of thrombin was decreased to the control level, as seen when recirculation with thrombin alone was performed. It is concluded that disappearance of thrombin enzymatic activity from a solution when recirculated through the microcirculation can be considerably increased if recirculated together with heparin, which probably reacts with endogenous antithrombin III on the vessel wall. The disappearance of thrombin in the absence of heparin was, however, unaffected by antithrombin III. The latter finding is compatible with the hypothesis that, in the microcirculation, antithrombin III/glycosaminoglycans play only a minor role for inhibition of thrombin coagulant activity and that thrombin binds mainly to thrombomodulin.

Animals↗

[Microcirculation of the liver in hemorrhagic shock in the rat and its significance for energy metabolism and function].

INTRODUCTION: Shock induced microcirculatory failure is proposed to be causative for the impairment of hepatic function, which contributes to the development of multiple organ failure. In order to quantify the interrelation between hepatic microcirculatory disturbances and organ dysfunction, we have analyzed hepatic microcirculation (in vivo microscopy), energy metabolism (ketone body ratio) and liver excretory function (bile flow) during hemorrhagic shock in rats. METHODS: Under chloralose anesthesia and mechanical ventilation Sprague-Dawley rats (n = 6) were laparotomized and the left liver lobe was exteriorized for in vivo fluorescence microscopy. Sinusoidal perfusion was assessed after i.v. injection of Na-fluorescein (2 mumol.kg-1), in vivo staining of white blood cells by Rhodamin-6G (0.1 mumol.kg-1 i.v.) enabled for analysis of leukocyte-endothelium interaction. Erythrocyte flux was measured by means of laser Doppler flowmetry. Hepatic function was estimated by measurement of bile flow via cannulation of the common bile duct. Ketone body ratio (acetoacetate/beta-hydroxybutyrate, Ac-Ac/beta-OHB) was measured spectrophotometrically from arterial blood and served as indicator of hepatic energy metabolism (n = 12). After baseline recordings hemorrhagic shock (MAP: 40 mmHG) was induced by blood withdrawal and maintained for a total of 2 h. Measurements were performed during baseline as well as 1 h and 2 h after induction of hemorrhage. RESULTS: After 1 h and 2 h of hemorrhagic shock sinusoidal perfusion was found markedly impaired (p < 0.05) from 100% (baseline) to 78.3 +/- 2.4% and 60.9 +/- 13.4%, accompanied by a significant fall of erythrocyte flux to 52 +/- 2% and 46 +/- 4% (p < 0.05). Leukocyte velocity was significantly (p < 0.05) reduced both in sinusoids and in postsinusoidal venules, while leukocyte adherence to the endothelial lining cells was found increased (sinusoids: 183.2 +/- 55.6% and 178.8 +/- 39.0% (p < 0.05); postsinusoidal venules: 232.4 +/- 43.1% and 297.6 +/- 65.8% (p < 0.05)). In addition, 2 h of hemorrhagic shock caused an increase of beta-OHB, while Ac-Ac levels remained unchanged. This resulted in a significant reduction of ketone body ratio. Concomitantly, bile production was significantly decreased from 20.8 +/- 2.9 microliters.min-1 during control to 6.1 +/- 1.0 microliter.min-1 after 2 h of shock (p < 0.05). The alteration of energy metabolism and the impairment of bile flow correlated significantly (p < 0.01) with the extent of microcirculatory disturbances. CONCLUSION: Liver microcirculation in hemorrhagic shock is characterized by sinusoidal perfusion failure with a reduction of erythrocyte flux, leukocyte velocity and enhancement of leukocyte adherence to the microvascular endothelial lining. Correlation of the impairment of energy metabolism and liver dysfunction with these microcirculatory disturbances may indicate their crucial role in the development of shock-induced organ failure.

Animals↗

Influence of diabetic neuropathy on skin microcirculation assessed by transcutaneous oxymetry.

Skin microcirculation was investigated in 45 patients with long term diabetes and with severe, moderate or no neuropathy, and in 15 controls. Transcutaneous oxygen pressure (tcPO2) measurements on the forefoot were performed at 37 degrees C to assess local capillary flow at rest, during leg dependency and reactive hyperaemia, and also at 44 degrees C, including the response to oxygen inhalation. TcPO2 (37 degrees C) at rest was significantly elevated with an increasing degree of neuropathy (Controls: 4.8 +/- 3.7; patients without neuropathy: 4.2 +/- 2.9; with moderate neuropathy: 6.0 +/- 2.9 (p < 0.01); with severe neuropathy: 7.2 +/- 4.2 mmHg (p < 0.001)). Leg dependency resulted in a decrease of tcPO2 in the controls, while an increase was observed in 18.6% of the measurements in patients, reflecting a disturbed vasoconstrictor response. Regardless of neuropathy, absolute tcPO2 values during reactive hyperaemia were reduced in all patient groups as well as tcPO2 (44 degrees C) and its increase during oxygen breathing. Diabetic neuropathy is likely to increase local capillary flow, while the other differences to healthy controls may be contributed to a microcirculation disorder independent of neuropathy.

Adult↗

Influence of sonographic contrast media on microcirculation in rats.

In an open placebo-controlled study the influence of the injection of different sonographic contrast media on the microcirculation was proved. The study was performed in 7 Sprague-Dawley rats. In order to examine this query two different sonographic contrast media in comparison to agitated electrolyte solution (as the placebo) were injected into the abdominal aorta of 7 anaesthetized rats as a 2 ml/kg bolus at 10-min intervals. Examined were a newly developed agitated ultrasound solution (AK I: an aequeous solution of a vegetable phospholipid) and a radiographic contrast agent (AK II: 741 mg Ioversol or 350 mg iodine, respectively, per ml) which is used in an agitated form as ultrasound contrast agent, too. 1 min before and until 2 min after each injection the capillary perfusion of the same vessel area in the major omentum was measured (video-recording by use of intravital microscopy). The erythrocyte velocity was determined off-line by an image analysing system. Whereas the agitated X-ray contrast medium AK II decreases the mean capillary perfusion (temporary flow stagnation in single capillaries), AK I as well as agitated electrolyte solution did not influence the capillary erythrocyte velocity in the major omentum. The gaps which appeared immediately after the injection of AK I seem to have been brought about by spherosomes of AK I. Still the spherosomes are so small that they can pass through the capillaries, or if they are larger which cannot be determined using in vivo microscopy the flow force necessary for the deformation of the bubbles is so small that the capillary perfusion is not influenced. The injection of agitated AK I does not lead to significant changes of the microcirculation.

Animals↗

Visualization and quantitative analysis of leukocyte dynamics in retinal microcirculation of rats.

PURPOSE: Recent studies have demonstrated that leukocytes play an important role in microcirculatory flow disturbances. A few methods are available to investigate leukocyte dynamics in retinal microcirculation. The authors explored leukocyte dynamics in the retina of rats with acridine orange digital fluorography. METHODS: Acridine orange digital fluorography produces high-resolution images from a scanning laser ophthalmoscope with the use of a fluorescent nuclear dye of acridine orange, which has been used for staining nucleic acids of cells in histochemical and cytochemical studies. The images were recorded on S-VHS tapes and were investigated with a personal computer-based image analysis system. RESULTS: Fluorescent leukocytes in the retinal microcirculation were visualized. Highly magnified images could be obtained because of the high dioptric power of the rat eye compared with the primate eye. It was possible to observe leukocyte deformation in narrow capillaries and nuclei of vascular endothelium. At arteriolar bifurcations, leukocytes moved preferentially into the branch with the higher flow rate. "Preferential channels" were identified in which predominantly leukocytes were delivered; the channels were characterized by high flow velocity and a straight, short capillary route. The average leukocyte velocities of the arteries, veins, and capillaries are 29.5 +/- 7.3, 17.4 +/- 5.3, and 1.4 +/- 0.4 mm/second, respectively. CONCLUSIONS: This study demonstrates that microcirculatory dynamics of leukocytes can be visualized and analyzed quantitatively in rats in vivo with acridine orange fluorography. This method may be a promising tool to reveal how leukocytes contribute to retinal flow disturbances under various pathologic conditions.

Acridine Orange↗

[Relationship between disturbances of microcirculation and TNF during burn shock].

The changes in microcirculation and the level of plasma TNF in rat at the early stage of burn shock were measured, and the effects of Polygonum cuspidatum (PC) on above mentioned changes were observed. It was shown when the level of plasma TNF was increased, the number of adhesive leukocytes on venule wall was increased and the number of open capillaries were reduced significantly, and there were apparent aggregation of leukocytes and injury in lungs. The level of plasma TNF and the number of adhesive leukocytes were nearly normal, and the degree of aggregation of leukocytes and injury of lungs were attenuated by giving PC. The present study showed that the level of elevated plasma TNF in the early stage of burn shock was directly correlated with the adherence of leukocytes and the closing of capillaries. The administration of PC could apparently inhibit the increase of leukocytes, and at the meantime, attenuate the adherence of the neutrophils and injury of the lung. The results confirmed that the elevation of plasma TNF might be involved in the development of adherence of neutrophils and the disturbances of microcirculation in burn shock.

Animals↗

Effects of prolonged blockade of the renin angiotensin system on striated muscle microcirculation of spontaneously hypertensive rats.

Changes in microcirculation play an important role in the pathogenesis and maintenance of hypertension. The changes can be due to an alteration in vessel diameter or in the number of small blood vessels. In this study, the effects of prolonged administration of different blockers of the renin angiotensin system on the microcirculation of the cutaneous maximus muscle of young spontaneously hypertensive rats were determined by using the dorsal microcirculatory chamber model. Animals were treated with the angiotensin-converting enzyme inhibitor (ACE inhibitor) benazeprilat (3 mg/kg/d) or the specific angiotensin II AT1 receptor antagonist valsartan (3 mg/kg/d) for 4 weeks. Blood pressure was significantly lowered by 22 to 33% and to a similar extent in both treatment groups, whereas blood pressure in the control group continued to rise. Microvascular diameters and density were measured before and during the drug treatment and compared with those in the control group. There was no significant effect of either of the drug treatments on vascular diameters when compared with the control group for any vessel type (arterioles or venules). In contrast, there was a significant decrease in small arteriolar and venular density and in large venular density after treatment with the ACE inhibitor, whereas the angiotensin II AT1 receptor antagonist had no significant effect. The data do not suggest a role for angiotensin II in the long-term control of striated muscle microvascular tone. However, angiotensin II may be involved in microvascular growth via a non-AT1 receptor-mediated mechanism, or other vasoactive peptides degraded by ACE may contribute to the effects of the ACE inhibitor.

Angiotensin Receptor Antagonists↗

Time-course of changes in nicardipine effects on microcirculation in retina and optic nerve head in living rabbit eyes.

The effects of intravenous administration of a calcium antagonist, nicardipine, on microcirculation in the retina and optic nerve head (ONH) of rabbit eyes were investigated using a laser speckle microcirculation analyzer. The rabbit fundus was illuminated by an argon (blue) laser spot to measure the retina or by a diode laser spot to measure the ONH, and the image speckle was detected by an image sensor. The difference between the average of the speckle intensity (Imean) and the speckle intensity for successive scannings was calculated, and the ratio of Imean to this difference was defined as normalized blur (NB); a quantitative index of blood velocity in tissue. The average NB over the field measured (0.62 x 0.62 mm in the retina and 0.42 x 0.42 mm in the ONH) was calculated to give NBav, which was found to show a significant correlation with the retinal blood flow rate determined using a microsphere technique. In Dutch rabbits for measurement in the retina and in albino rabbits for measurement in the ONH (nicardipine group), 0.4 mL/kg of 0.01% nicardipine hydrochloride dissolved in physiological saline was injected intravenously into anesthetized animals. To serve as control, other groups of Dutch or albino rabbits were injected with 0.4 mL/kg of physiological saline. Mean femoral arterial blood pressure (FABPm) in the nicardipine group dropped to the minimum at 1 minute post-injection and this level remained significantly lower than that in the control group up to 15 minutes post-injection. The pulse rate, pH, Pco2 and Po2 of arterial blood, body temperature and the intraocular pressure did not show any significant changes during the experiment. The NBav obtained from the retina in the nicardipine group showed a significant transient decrease, probably due to the initial drop in the FABPm, followed by a significant increase after the FABPm returned to the baseline. The time-course of NBav obtained from the ONH in the nicardipine group showed little change. These results suggest that nicardipine may have considerable potential in the treatment of ocular diseases associated with insufficient retinal blood flow. The nicardipine effects observed here deserve to be studied further in human eyes.

Animals↗

The role of nitric oxide and cell adhesion molecules on the microcirculation in ischaemia-reperfusion.

The microcirculation undergoes a profound degree of endothelial dysfunction within minutes (i.e., 2.5 to 5 min) following reperfusion of ischaemic vasculature. This has been documented in the coronary and mesenteric microcirculation. The endothelial dysfunction is characterized by a loss in basal and agonist-mediated nitric oxide (NO) produced by the vascular endothelium. The loss of NO results in upregulation of cell adhesion molecules (CAMs) particularly P-selectin 10-20 min following reperfusion. Thus, CAM upregulation renders the endothelium sticky, and a marked degree of leukocyte adherence (particularly neutrophils) occurs 20 min following reperfusion. This enhanced involvement of neutrophils leads to neutrophil infiltration into the underlying tissue (e.g., myocardium) within 2-3 h of reperfusion. The infiltration of neutrophils leads to reperfusion injury (i.e., necrosis) which is significant at 3 h but becomes profound at 4.5 h following reperfusion. Cardiac necrosis can be significantly attenuated by treatment with NO, an organic NO donor, L-arginine, or specific blockers of CAMs given just prior to reperfusion. This approach is a promising one for a variety of types of reperfusion injury.

Animals↗

The microcirculation in venous hypertension.

OBJECTIVE: To review the factors that result in skin ulceration of patients with chronic venous insufficiency. DATA SOURCES: Index Medicus was searched using an on-line computer system for years 1966-1995 to identify articles relating to venous ulceration and the microcirculation. DATA EXTRACTION: Articles and sections of articles relating to the mechanisms which cause venous ulceration and the efficacy of the treatment of venous ulceration have been included. DATA SYNTHESIS: It seems unlikely that venous ulceration is attributable to failure of diffusion of oxygen and other small nutritional molecules to the tissues of the skin. It is much more likely that neutrophils attach themselves to the cutaneous microcirculation, become activated and produce endothelial injury. Repeated over many months or years, this leads to the chronic inflammatory process of lipodermatosclerosis. The microvascular changes in the skin are characterised by activated endothelium and perivascular inflammatory cells. CONCLUSION: There is evidence of leucocyte involvement in the pathogenesis of venous ulceration. The exact mechanisms remain to be resolved. Improved treatment for patients may be devised with a better understanding of the basic causes of this condition.

Humans↗

Clinical implications of impaired microcirculation.

Various types of microcirculation disturbances have been described in the course of systemic diseases, hypertension, diabetes, obesity, and the so-called "idiopathic oedema" syndrome. This article summarizes the relevant microcirculatory disorders associated with diabetes and their pathophysiology. These functional disorders occur before or in association with anatomical lesions of diabetic microangiopathy. Increased capillary permeability to albumin is frequently observed in diabetes. In a placebo-controlled trial, Daflon 500 mg, a purified, micronized, flavonoidic fraction, significantly improved this disorder. Patients complaining of an oedematous syndrome almost always have an increased extracellular fluid volume, probably largely due to increased capillary permeability. Diabetes and "idiopathic oedema" therefore constitute two examples of the major clinical implications of impaired microcirculation.

Capillary Permeability↗

[Macro- and microcirculation study in diabetic patients].

In diabetics, vascular examination may consider great and medium arteries and microcirculation. The aim of this study is correlation between stenosis in carotid and femoral bifurcation, ultrasound biopsy, and laser-Doppler measurements of distal microcirculation in diabetics. During a six month period, we have examined 90 diabetics in the diabetological service of the Civita Castellana Hospital (Viterbo, Italy), asymptomatic for any vascular distal, cerebral or coronary disease. Subjects were 49 +/- 20 years old with 15 +/- 5 years of diabetes; glycosilate haemoglobin was 7% (mean). 70% of diabetics (62% type I, 38% type II) had an altered veno-arteriolar reflex and 30% of these an ultrasound biopsy value of more than 25. These data demonstrate that most diabetic subjects develop an early, preclinical neuropathy that is directly proportional to the arterial wall condition.

Adult↗

Reversibility in blood-brain barrier, microcirculation, and histology in rat brain after decompression.

To examine the changes in blood-brain barrier (BBB), cerebral microcirculation, and histology from 15 min to 72 h after decompression, 90 rats were exposed to experimental compression to 6 atm abs air for 90 min and subsequent rapid decompression. The disruption of BBB was examined by Evans blue extravasation. The cerebral microcirculation was demonstrated by perfusion with India ink. The area stained with Evans blue and the regions of defective filling with India ink, observed immediately after decompression decreased in size with time and were undetectable 3-24 h after decompression. The edematous brain tissue with enlarged perivascular space and darkly stained nerve cells also decreased to the uncompressed control level 1-24 h after decompression. These reversible dysbaric changes, however, reappeared 48-72 h after decompression. The different mechanisms, the physicochemical effects of microbubbles, and the maturation phenomenon after temporary brain ischemia induced by dysbaric microbubbles may be involved in the brain damage after decompression sickness.

Animals↗

Early events of metastasis in the microcirculation involve changes in gene expression of cancer cells. Tracking mRNA levels of metastasizing cancer cells in the chick embryo chorioallantoic membrane.

The early events of metastasis involve multiple interactions between cancer cells and the host microcirculation during cancer cell arrest, adhesion, and extravasation. These interactions may lead to changes in gene expression of the metastasizing cancer cells, although such changes have never been demonstrated directly. To test this hypothesis, B16-F10 murine melanoma cells were injected intravenously into the chick embryo chorioallantoic membrane (CAM), and mRNA levels in the metastasizing cancer cells were evaluated by species-specific reverse transcription polymerase chain reaction. Unlike standard mouse models of experimental metastasis, the CAM model showed successful extravasation of a large number of the arrested cancer cells in the CAM microcirculation without significant cancer cell death, providing a unique opportunity to keep track of mRNA levels in cancer cells during the early phases of metastasis. Using this model, we were able to demonstrate directly the temporal induction of cancer cell genes that potentially affect metastatic efficiency, namely, Fos (5 to 60 minutes after injection), vascular permeability factor (4 to 7 hours), and urokinase plasminogen activator (> 9 hours). In conclusion, using the CAM system, we have observed an alteration of gene expression in cancer cells in the early phases of metastasis, most likely as a consequence of host-cancer cell interactions. These changes may influence the metastatic behavior of cancer cells.

Actins↗