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Adenine nucleotides and carbohydrates in subpopulations of hepatic nodules with normal and compromised microcirculation.

Fluorescein-isothiocyanate dextran (FITC-dextran), a dye confined to the vascular space, was infused via the hepatic artery and portal vein into perfused livers from fed rats treated with diethylnitrosamine for 4 to 5 months. Fluorescence due to FITC-dextran was detected with fiberoptic microlight guides placed on surface nodules of about 5 mm in diameter. Nodules were categorized into groups with normal and compromised microcirculation based on their fluorescence following infusion of FITC-dextran. Similar results were obtained when nodules were classified based on reflectance of trypan blue. Despite compromised microcirculation, ATP and ADP levels as well as ATP/ADP ratios were comparable in both groups of nodules; however, AMP was elevated in FITC-dextran-negative nodules (i.e., those with compromised microcirculation). Nodules with compromised microcirculation also contained higher glucose and lactate levels than nodules that were well perfused; however, glycogen was five times lower than in FITC-dextran-positive nodules. Fasting reduced ATP/ADP ratios in poorly perfused nodules in comparison to well-perfused nodules. In perfused livers from fed rats where glycogen was high, however, ATP/ADP ratios and rates of ATP depletion during ischemia were the same in well-perfused and poorly perfused nodules. Products of glycogen breakdown (e.g., glucose and lactate) were elevated in nodules from livers of fed but not fasted rats. The results indicate that alteration of perfusion of hepatic nodules does not change ATP levels nor the capacity of nodules to utilize high energy phosphate during anoxia. Thus, near normal energy status is maintained from glycogen metabolism in poorly perfused nodules via glycolysis. Since basal ATP content and utilization is comparable in well and poorly perfused nodules, compromised energy status is unlikely to explain selection of nodules that regress to near normal hepatocytes.

Adenine Nucleotides↗

[Correlation between hepatic microcirculation ultrastructural changes and hepatic dysfunction in chronic hepatitis B].

The author observed the ultrastructural changes of hepatic microcirculation and the function of the liver in 41 cases with chronic hepatitis B confirmed histologically. The main ultrastructural changes found in patients were swelling of the endothelium of hepatic sinusoids, hyperplasia of Kupffer cells and decrease of fenestrae in the endothelium. Proliferation of monocytes and fat-storing cells was also found in the lumina of hepatic sinusoids and space of hepatocytes and perisinusoid. The basement membrane in hepatic sinusoids and the base of hepatocytes were formed in the patients with marked pathologic changes of the liver, especially in CAH with cirrhosis. The observations also showed that whatever extent of hepatic microcirculation changes, all of them had more or less elevation of SGPT and ZnT or TT. As soon as hepatic function was impaired slightly, there occurred hepatic dysmicrocirculation. But in the cases of severe ultrastructural hepatic dysmicrocirculation serum gamma globulin elevation values and A/G ratio exchanges were much higher than those in the cases of slight changes. There was some significance on the judgment of sick condition, slight or severe. Values of the elevation of serum gamma globulin and A/G ratio exchanges were much more obvious than SGPT, ZnT and TT changes. These findings suggest that the extents of pathological changes and dysfunction of the liver in chronic viral hepatitis B are correlated to the extent of hepatic microcirculation impairment. So in the treatment of chronic hepatitis early administration of medicine to improve the liver microcirculation should be considered.

Adolescent↗

[Results and prospects for the study of the morphologic basis of microcirculation of the blood].

The survey of the works, performed during the 11th five-year period in studying general biological regularities of microcirculation, demonstrates certain success in investigations developed in the following directions: functional geometry of the hemo-microcirculatory bed; elaboration of quantitative and qualitative analysis methods of the microcirculatory system elements; functional morphology of the vascular endothelium; experimental analysis of adaptive mechanisms of the microcirculatory bed; clinical-morphological investigations of microcirculation. Formation of structural-functional units, ensuring specialization of microcirculation in organs, forms the base of the functional geometry of the microcirculatory bed. This makes necessary conditions for compartmentalization of some micro-region in an organ and spatial distribution of various liquid media in dependence of certain topology of microvessels. The most perspective ways in development of morphological investigations, concerning the general biological regularities of microcirculation, are discussed.

Animals↗

[Morphofunctional characteristics of the conjunctival microcirculation of students of different regions of the world].

By means of vital microscopy, the conjunctival microcirculation has been estimated in students from various regions of the world depending on duration of the time of their life in the USSR. Adaptive rearrangements of the conjunctival microcirculation of the eye ball have been revealed in various time of adaptation. Integral estimation of the conjunctival microcirculation has demonstrated that at initial phase of adaptation synchronization in the work of separate links of the microcirculatory bed is observed. These changes can be interpreted as strain of the compensatory mechanisms. In two years of study, certain stabilization of the microcirculation system activity is observed in the foreign students; this can be considered as the phase of stable adaptation. In the students arrived from hot regions of the world, pigmentation in the eye ball conjunctiva has been revealed. By means of the correlative analysis it has been demonstrated that the pigmentation influences the most labile parts of the microcirculatory bed-capillaries and venules. Pigmentation is usually regarded as a pathological sign peculiar for some diseases. Our investigations have demonstrated that pigmentation should be interpreted carefully and the place of residence of the students investigated should be taken into account, since pigmentation can be the result of elevated solar radiation, specific for hot regions of the Earth.

Acclimatization↗

[Overacidified tissue and microcirculation (author's transl)].

A discussion of physiological fundamentals with respect to the inhibition of blood microcirculation in (tumor) tissue at reduced pH values around 6.0 is followed by a report on principles, design and results obtained with a light probe array which permits to determine in vivo reference values of the relative intensity of microcirulation in both normal and tumor tissues under various conditions. An analysis of the discussed records has shown that--as compared to a value of 80-66% without glucose infusion--the relative mean intensity of microcirculation in tumor tissue drops to approximately 8-4% about 300 min after the onset of glucose infusion under CMT administration at 37 degrees C. By adding the CMT step of hyperthermy, the relative mean intensity of microcirculation--compared to normal tissue at 37 degrees C--will further drop below 1%. With such a decline of microcirculation--and an adequate duration of, say, 8 hours--local hyperthermy at 41-42 degrees C is likely to cause a very pronounced damaging action on tumor tissue because the then noticeably reduced substrate offer proves to be insufficient to ensure the structure-maintaining metabolic rate of cancer cells.

Animals↗

[Differences in induction of the cellular switch mechanism of blood microcirculation in various organs and tissues of the human body].

Different effects of a bad oxygen state of the organism on several organs an tissues as well as observed differences in their response to a lasting restoration of a good oxygen state by the Oxygen Multistep Therapy (O2MT) initiated the search for the (common) cause of these differences. From the view of our O2MT research, the organ- and tissue-specific different levels of the switching threshold of the bioenergetically controlled switching mechanism of blood microcirculation were suspected to be decisive. Observations discussed here revealed that this switching threshold is controlled by the local venous pO2 values and the capillary blood-flow. When the microcirculation is initially little changed (starting situation), the pathogenic lowering of microcirculation in different organs and tissues is mainly dependent on the venous oxygen partial pressure. From a scale containing venous pO2 values of different organs and tissues for two ages on can obtain the following order of succession with increasing pO2-ven: heart, lower extremities, brain (circulatory disorders), upper extremities, lungs, liver, stomach and bowel, skin, kidneys, spleen. This order agrees well with clinical findings on the frequency of diseases and disorders in different organs in relation to the increasingly insufficient oxygen state (progressing age). On the other hand, this sequence is also in good correlation with clinical observations, which are given here and show the abolition of pathogenic disturbances in different organs and tissues after "step-up" of microcirculation by means procedures of the O2MT. Finally, the abrogation of peripheral circulatory disorders of the lower extremities is discussed as a paradigm. The specific feature of this disease is to additionally weaken the oxygen state of the organism by the constraint in ability to move.

Adult↗

Rheology in the microcirculation in normal and low flow states.

A brief review is given for the rheological behavior of blood in the microcirculation in normal and low flow states. Blood viscosity increases in low flow conditions because of the decrease in shear stress which normally causes red cell deformation and disaggregation. The low hematocrit found in the microvessels leads to a decrease in apparent blood viscosity and tends to compensate for the high vascular hindrance due to the narrowness of the vessels. The presence of the less deformable white blood cells in the microcirculation causes a retardation of red cell flux and a redistribution of red cells at bifurcations. Elevated hematocrit, in turn, can cause an enhancement of the interaction between white blood cells and the venular endothelium. Adhesion of white blood cells to microvascular endothelium leads to an increase in flow resistance, especially in low flow states. The optimum hematocrit for myocardial oxygen transport and utilization is shifted from near 40% in normal conditions to 25% in hemorrhagic hypotension. These findings indicate that blood rheology in the microcirculation should be considered in analyzing the pathophysiological disturbances in shock and that improvement of microcirculation rheology offers a promising approach in treatment.

Biological Transport↗

Quantitative evaluation of leukocyte dynamics in retinal microcirculation.

PURPOSE: Leukocyte rheology may play a key role in microcirculation because leukocytes have unique properties, such as large cell volume, high cytoplasmic rigidity, and low deformability. However, only a few methods are available to study the dynamic behavior of leukocytes in retinal microcirculation. The authors developed a new method to analyze directly movements of leukocytes in the retinal vessels of primates. METHODS: Acridine orange, which has been used as a nuclear stain in histochemistry and cytochemistry, was injected intravenously into cynomolgus monkeys for a vital staining of leukocytes. The fundus image was generated with the argon blue laser and a scanning laser ophthalmoscope. The images were recorded on a magnetic tape and evaluated with a personal computer-based image analysis system. RESULTS: Each leukocyte was recognized as a single fluorescent dot moving in the retinal vessels. It was possible to analyze the spatial and temporal dynamics of individual leukocytes in the capillaries. Some leukocytes passed through the capillaries, plugging transiently under the physiological condition. Leukocytes that stayed in the same position for a few minutes may have stuck to the endothelium as a result of leukocyte-endothelial interactions. In the postcapillary vessels, leukocytes tended to be displaced from the center stream toward the vessel walls. The mean flow velocity of leukocytes in the perifoveal capillary was 0.92 +/- 0.32 mm/sec. CONCLUSIONS: This study clearly demonstrated that rheologic behaviors of leukocytes in the retinal microcirculation can be studied through the vital staining with acridine orange in vivo. The authors' results suggest a potential role of leukocytes in retinal vascular flow disturbances. This study may open the door to the investigation of leukocyte hemodynamics in the retinal microcirculation in vivo.

Acridine Orange↗

[Morphological study of the microcirculation in regional cortical bones affected by internal fixation plates].

In order to elucidate the potential role of bone microcirculation in the development of plate-induced regional osteoporosis, microangiography was used to observe the morphological changes of microcirculation in cortical bones obtained from intact rabbit tibiae on which plates of two different stiffness had been fixed for comparison. The results indicated that both rigid stainless steel plates and less rigid methyl methacrylate plates could induce the bone microcirculation under and opposite the plate to undergo a changing process from early depression to later reactive recruitment. The features of the microcirculation recruitment as shown in vascular number, arrangement and dilatation varied with different stiffness plates and in different locations, and might also have bearing on the formation of osteoporosis.

Animals↗

[Curative effect of combined traditional Chinese medicine with Western medicine therapy on chronic nephritis and its correlation with hemorheology and microcirculation].

Patients were divided into two groups, 89 cases treated by combined traditional Chinese and Western medicine (TCM-WM) therapy, the other 36 served as control. Each of two groups was further subdivided into 4 clinical types and 5 Syndromes of TCM. Hemorheology and microcirculation were tested before and after treatment, the clinical curative effects of both groups were compared and correlation analysis between clinical curative effect and improvement of hemorheology and microcirculation was made. The results showed that the remission rate and total effective rate were 79.8% and 92.1% respectively in testing group, significantly higher than those (25% and 50%) of control (P < 0.05-0.01). The curative effect on each clinical type and Syndrome of TCM was better than that on corresponding type and Syndrome of control (P < 0.05-0.01). The improvement of hemorheology and microcirculation was more significant in testing group than that in control. It was very significant in complete and partial remission of both group (P < 0.05-0.01) but not marked in the cases of improved and ineffective cases (P > 0.05). Therefore clinical curative effect was closely related with them. So any treatment which could improve hemorheology and microcirculation would be useful in treating chronic nephritis.

Adult↗

Mechanics of blood flow in the microcirculation.

The microcirculation in most tissues consists of an intricate network of very narrow tubes. In analyses of blood flow through the microcirculation, inertial effects can be neglected, but continuum models for blood cannot be assumed, since blood is a concentrated suspension of cells with dimensions comparable to vessel diameters. These cells strongly influence blood flow. About 45% of blood volume consists of red blood cells, whose key mechanical properties are known. A red cell has a fluid interior, surrounded by a flexible membrane, which strongly resists area changes, but bends and shears easily. White blood cells are comparable in size but much less numerous. They are less flexible than red cells and capable of active locomotion. Other suspended elements are much smaller than red cells: This review focuses on the mechanics of red cell motion in the microcirculation. Experimental and theoretical studies of blood flow in uniform tubes, bifurcations and networks are discussed. Comparisons between predicted and observed flows in networks imply that resistance to blood flow in living microvessels is higher than that in uniform tubes with corresponding diameters. Living microvessels have non-uniform geometries, and red cells must deform continually to traverse them. Theoretical results are presented implying that these transient deformations contribute to increased flow resistance in the microcirculation.

Animals↗

[Study on relationship between nail-fold microcirculation and histopathology of patients with vocal cord polyp and blood stasis syndrome].

Nail-fold microcirculation of 50 vocal cord polyp patients was observed and compared with hoarseness patients without vocal cord polyp. The results showed that peripheral microcirculation was disturbed in the vocal cord polyp patients. Histopathologic observation of 200 vocal cord polyp patients was made. It was found that principal pathologic change concentrated on the lamina propria mucosae of vocal cord and the most prominent manifestation was disturbance of topical microcirculation of Reinke's layer. In microcirculation aspect, the relationship between polyp of vocal cord and the Blood Stasis Syndrome was confirmed, and pathogenic mechanism of vocal cord polyp was discussed.

Adult↗

[Functional evaluation of an experimental model of cutaneous microcirculation and pO2 after surgical excision: traditional method vs laser CO2].

Within an experimental study project about the interaction between Laser and biological tissues, the authors utilized a Laser Doppler Flowmeter device and a Polarographic method to study the cutaneous microcirculation and the tissue pO2. Under standardized conditions, the experimental model considered the microcirculation measurement and the ptiO2 before and after the exsection of a cutaneous lozenge on the animals back realized with traditional surgical methods (scalpel and electrotome) or with a last generation CO2 Laser in continuous and in pulsed mode. The Laser Doppler Flowmeter showed that the largest perturbation of the microcirculatory flux occurred after the exsection realized with the scalpel and the electrotome. The CO2 Laser utilized in continuous mode showed an influence slightly lower on the microcirculation while in pulsed mode the perturbation was absent. The ptiO2 measurement showed similar results emphasizing that the CO2 surgical Laser technique is less invasive than the traditional. To sum up, these functional methods allowed a careful microcirculation an ptiO2 evaluation and provided useful information about vasal and metabolic alterations, showing that the CO2 surgical Laser utilized in pulsed mode appears to be the less harmful surgical technique for the tissues surrounding the exsection site.

Laser-Doppler Flowmetry↗

Microcirculation of the fingernail fold in CAPD patients: preliminary observations.

OBJECTIVE: To study changes in the peritoneal microcirculation during continuous ambulatory peritoneal dialysis (CAPD) by studying change in the microcirculation of the fingernails of CAPD patients. SETTING: A university department. DESIGN: A cross-sectional study of 10 nondiabetic patients on CAPD. INTERVENTION: Hemorrheological tests of fingernail microcirculation using equipment built at our university. MAIN OUTCOME MEASURES: Microcirculation was characterized by estimation of capillary density, red blood cell (RBC) column diameter, torque index, and RBC flow velocity semiquantitatively using videocapillaroscopy at the fingernail fold and plasma viscosimetry. Findings were correlated with treatment duration, peritoneal clearance, state of capillary morphology and hemodynamics, and lipid and fibrinogen levels. RESULTS: Treatment duration was significantly correlated (p < or = 0.05) with low-density lipoprotein (LDL) (r = 0.776) and clearances of urea (r = -0.583), uric acid (r = -0.666), and potassium (r = -0.764). Changes in capillary morphology were correlated to clearances of urea (r = 0.643) and uric acid (r = 0.701). The fibrinogen concentration increases plasma viscosity (r = 0.799) and deteriorates the capillary state (r = -0.706). In addition, plasma viscosity correlates to cholesterol (r = 0.620, NS) and LDL (r = 0.781), but not to high-density lipoprotein and triglycerides. CONCLUSION: CAPD treatment results in lipid abnormalities and high fibrinogen levels that may cause microvascular damage and poor perfusion. These interactions may explain the deterioration of peritoneal transport in some CAPD patients.

Adult↗

[Effects of hyperoxia on the behavior of leukocytes in rat pulmonary microcirculation assessed by confocal laser scanning microscopy].

To study the dynamic interaction between blood cells and endothelial cells in the pulmonary microcirculation, we developed a method for observing leukocytes and erythrocytes in the microcirculation of perfused rat lungs by confocal laser scanning microscopy. We examined the behavior of leukocytes in the microcirculation of rat lungs exposed to hyperoxia, because oxygen toxicity is known to be associated with leukocyte infiltration and endothelial cell damage. Rats were divided into two groups: control (21% O2) and hyperoxia (90% O2 for 48 hours). Lungs were perfused with Krebs-Henseleit solution equilibrated with 21% O2 and 5% CO2 through an artificial lung. Leukocytes stained with carboxyfluorescein diacetate succinimidyl ester and erythrocytes stained with fluorescein isothiocyanate were added to the perfusate, and images of the cells were observed and recorded with a confocal laser scanning microscope and a high-speed video camera. The mean velocities of erythrocytes (Vr) in arterioles, capillaries, and venules of the control group were 1.52, 0.50 and 1.61 mm/sec, respectively. Also in the control group, the velocities of the leukocytes were divided by the mean velocities of the erythrocytes in the same arterioles, capillaries and venules (Vw/Vr) and the results were 0.96, 0.97, and 0.98, respectively. The Vw/Vr values for arterioles in the hyperoxia group were not significantly different from those in the control group, but the Vw/Vr values for capillaries and venules were 27% and 37% lower than their respective control values. Leukocyte sequestration was seen mainly in capillaries in the hyperoxic group. These results suggest that an increase in adhesion in capillaries and venules, such as that caused by adhesion molecules, might play a key role in the behavior of leukocytes in the pulmonary microcirculation during hyperoxia.

Animals↗

Pulmonary microcirculation during pulsatile and non pulsatile perfusion.

During development of a rotary blood pump as an assist device, the efficacy of non pulsatile perfusion to the end organ has to be verified. However, there are few evaluations of two different perfusion mechanisms through the tissue microcirculation. In this study, the pulmonary microcirculation was analyzed by vital microscopic observation. Wistar rats weighing 400-500 g were anesthetized and ventilated by a respirator. After establishing right heart bypass from the right atrium to the pulmonary artery using a roller pump, the pulmonary microcirculation was observed during intravenous infusion of bovine albumin tagged with fluorescein isothiocyanate. The images were recorded on a videotape through an ultra-sensitive SIT TV camera. Initially, the pulmonary circulation was pulsatile, produced by the native heart, and the pulmonary capillary network was evenly perfused by the blood. After starting the pump, the flow became non pulsatile and the distribution of capillary perfusion was displaced to the short circuit connecting the pulmonary arterioles and venules. Flow distribution during non pulsatile perfusion was heterogeneous compared with pulsatile perfusion. This result suggests that non pulsatile flow may lead to the deterioration of function. Further investigation is necessary to evaluate the relationship between the microcirculation and organ function.

Animals↗

[The effect of early decompression on the extent of changes in spinal cord microcirculation in experimental traumatic injury to the cord in rabbits].

The purpose of the study was the assessment of the effect of compression of the spinal cord after traumatic injury on spinal microcirculation disturbances and the evaluation in what degree early decompression of the cord reduces the degree of these changes. The experimental study was carried out on 20 rabbits. The injury to the cord was produced at the Th9-Th10 level with simultaneous compression causing vertebral canal narrowing by 1/3 of its width. The assessment was based on the results of microangiographic qualitative and quantitative studies. The animals were divided into 4 groups depending on the duration of cord compression 2, 4, 6 and 12 hours. In each group microcirculation studies were done 12 hours after decompression. Prolonged compression was found to increase the extent of microcirculation disturbances, which were most pronounced after 6 hours of compression. In the group of 12-hour compression microcirculation improvement was observed near the focal lesion. It is concluded that possibly early decompression up to 6 hours after trauma can reduce the degree of secondary damage caused by ischaemia.

Animals↗

Life and death in the microcirculation: a role for angiotensin II.

OBJECTIVE: Angiotensin II (ANGII) plays a critical role in the maintenance of the microcirculation and in the anatomical loss of microvessels (rarefaction) that occurs in low renin forms of hypertension and in animals fed a high-salt diet. Elevations in sodium intake can trigger a series of hemodynamic and hormonal responses culminating in a substantial rarefaction of small arterioles and capillaries in both normal and reduced renal mass hypertensive rats. METHODS: Immunohistochemistry, Northern blot, and reverse transcription-polymerase chain reaction (RT-PCR) analysis of microdissected blood vessels were used to localize ANGII receptors in the microcirculation. Chronic infusion of ANGII and other physiologic and pharmacologic manipulations of the reninangiotensin system in rats was combined with morphologic and mathematical analysis of the network architecture. RESULTS: We have shown that rarefaction of the microcirculation can cause an increase in total peripheral resistance, reduced tissue perfusion, decreased oxygen delivery, and impaired organ function. Although the mechanisms by which this occurs are not well understood, a number of key observations point to a role for the renin-angiotensin system in this effect. First, ANGII infused systemically at subpressor levels, or locally into the skeletal muscle interstitium, can induce significant microvessel growth. Second, localization of ANGII receptor proteins by immunohistochemistry and Western blotting and RNA localization by RT-PCR confirm the presence of AT1 receptors, which are growth-stimulatory, and AT2 receptors, which are growth-inhibitory in the microcirculation. Third, maintenance of ANGII at normal levels during periods of hypertension or high-salt diet completely eliminates rarefaction. CONCLUSIONS: Taken together, these results support the hypothesis that ANGII acting through AT1- and AT2-receptor mechanisms modulate vessel density during high-salt diet and hypertension.

Angiotensin II↗