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Microcirculation patterns in different stages of melanoma growth.

Several microcirculation patterns in tumors have been reported, including vasculogenic mimicry (VM), mosaic vessels (MV) and endothelium-dependent vessels. To investigate the sources of blood supply during different tumor stages, we studied the correlation between expression of vasculogenic mimicry (VM), mosaic vessels (MV) and endothelium-dependent vessels in a mouse melanoma xenograph. Sixty C57 mice were divided into 12 groups (5 mice per group) and inoculated with B16 melanoma cells. Eleven days later, the average tumor size was approximately 0.2 to 0.3 cm. From days 11 to 22, one group per day was randomly sacrificed, and the density of vasculogenic mimicry, mosaic vessels and endothelium-dependent vessels was measured in tumor tissue sections. Immunohistochemical dual-staining and electronic microscopy were also used to confirm the vessel types. All three types of microcirculation patterns were observed during tumor development. In the early stage of tumor growth, vasculogenic mimicry is the main pattern of blood supply. As the area of tumor tissue expands and the number of endothelium increase, vasculogenic mimicry is replaced by endothelium-dependent vessels. Mosaic vessels might be the interim state between vasculogenic mimicry and endothelium-dependent vessels. The number of endothelium-dependent vessels correlated with the size of the tumor (r=0.718, P=0.009), while the number of vasculogenic mimicry was inversely correlated (r=0.77, P=0.003). In conclusion, the number of vasculogenic mimicry decreased and the number of endothelial-dependent vessels increased during tumor growth.

Animals↗

Engineering approaches to the microcirculation studies.

This review focused on a few methodologies which the author, with a background of chemical engineering, has developed in the physiological studies of microcirculation. (1) Fluorescent tracers to visualize mass transfer and hemodynamics: By means of a high sensitive SIT camera equipped in an intravital microscope system, dynamic processes of the permeation of a fluorescent dye from the microvessels through the extravascular space to lymphatics was made to be visualized. Dynamic behaviors of the formed elements were also quantitatively analyzed by the selective fluorescent labeling technique. (2) The dye/light method to induce platelet thrombus in vivo: Intravascular platelet aggregation and subsequent thrombus formation leading to the complete occlusion of the vessels were produced in the microvasculature by the irradiation of filtered light in combination with the intravascular administration of sodium fluorescein. This method enables quantitative evaluation of thrombus formation process in terms of thrombus formation times. Effects of hemodynamic parameters on thrombogenesis in vivo were quantitatively analyzed. (3) Establishment of peritoneal disseminated tumor model: Colon tumor cells (RCN-9) were inoculated into the peritoneal cavity of male Fischer rats, and the intravital microscopic observation of angiogenic vascular growth accompanying tumor growth was made possible. Dynamic behavior of leukocytes in the microcirculation of solid tumor tissue was visualized using a fluorescent labeling technique combined with the use of a real-time confocal laser-scanning microscope.

Animals↗

Vitamin C supplementation could reverse diabetes-induced endothelial cell dysfunction in mesenteric microcirculation in STZ-rats.

This paper was aimed to study whether vitamin C supplementation reverses the diabetes-induced endothelial cell dysfunction occurred in streptozotocin (STZ)-rats or not. The animals were divided into four groups: control and diabetes rats (DM, using iv. injection of 50 mg/kg.bw STZ), and two DM rats treated with vitamin C (1 g/l) starting on day 2 (DM + VitC(day2)) and week 6th after STZ-injection (DM + VitC(6wks)). The mesenteric microcirculation was observed using fluorescence videomicroscopy. Based on the recorded videoimages, microvascular responses to acetylcholine (Ach; 10-5 M) and number densities of leukocyte adhesion in venules were evaluated using the Global Lab II image software. In DM group, blood glucose and glycosylated hemoglobin were significantly increased, while the body weight and plasma vitamin C levels were decreased significantly compared to their controls. Ach-induced vasodilation was decreased, while the number of leukocyte adhesion was increased significantly compared to their controls (p<0.01). These abnormalities induced by DM were prevented by supplementation of vitamin C in DM + VitC(day2) group. Six-weeks delayed treatment of vitamin C (DM + VitC(6wks)) demonstrated increase in the Ach-induced vasodilation with significant decrease in the leukocyte adhesion. It was indicated that vitamin C supplementation could reverse diabetes-induced endothelial cell dysfunction in mesenteric microcirculation.

Animals↗

Physiologic microcirculation of the heterotopically transplanted rat liver with portal vein arterialization depending on optimal stent diameter.

BACKGROUND: Clinical experience with portal vein arterialization (PVA) in liver transplantation is controversial. One reason for this is the lack of standardized flow regulation. The present experiments aimed to establish flow regulation in the arterialized portal vein for heterotopic auxiliary liver transplantation (HALT), to obtain physiological portal blood flow, and to compare this technique with orthotopic liver transplantation. MATERIAL/METHODS: Lewis rats were divided into 7 groups (n = 8 transplantations/group). Group: A I-IV: In HALT, the portal vein was anastomosed to the right renal artery using stents with different diameters (0.2, 0.3, 0.4, 0.5 mm). Afterwards, HALT with PVA using the stent diameter that had achieved the most physiological portal blood flow (group B II) was compared with orthotopic liver transplantation with porto-portal anastomosis (group B III) and to the sham group (B I). RESULTS: After reperfusion, only the 0.3 mm stent resulted in an average blood flow in the arterialized portal vein in HALT which was within the normal range (1.7+/-0.4 ml/min/g liver weight). The parameters of microcirculation and early graft function were significantly better in group B II than in group B III (functional sinusoidal density: 335+/-48 vs. 224+/-31/cm, diameter of sinusoids: 6.4+/-0.6 vs. 5.2+/-0.6 microm, diameter of postsinusoidal venules: 31.1+/-3.3 vs. 25.5+/-2.0 microm, bile-production: 27+/-8 vs. 19+/-5 microl/h/g liver weight). CONCLUSIONS: Using an optimal stent diameter in HALT with portal vein arterialization, an adequate flow-regulation can be achieved. Avoiding portal hyper- and hypoperfusion, good results for microcirculation and early graft function can be obtained.

Animals↗

[The microcirculation of patients with arterial ischemia of the lower extremities during laser therapy].

Microcirculation in the patient's foot skin with different stages of arterial ischemia, was examined with the aid of TV-capillaroscopy, laser dopplerography, polarography of transcutaneous oxygen tension. The effect of semiconductor laser (wave length 0.98 mcm) on microcirculation system was studied. The dependence of capillary blood flow on the transcutaneous oxygen tension was determined. The laser therapy proved to be successful in the patients with the II and III stages of arterial ischemia.

Adult↗

[Microcirculation and the blood rheological properties and their correction in ischemic disorders of the cerebral circulation].

A study was made of microcirculation using bulbar biomicroscopy and of the aggregation properties of platelets in 94 patients with initial manifestations of cerebral circulatory failure and dyscirculatory encephalopathy before and after the treatment with vasoactive drugs and actovegin. It has been recorded that the impairment of blood microcirculation progresses with the rise of the disease stage, being more pronounced in patients with vegetovascular crises. To correct microcirculatory disorders and the rheological properties of blood, the authors provide evidence for administering cavinton, euphylline and nicotinic acid combined with actovegin.

Adult↗

[The introduction of thermodynamics in the theory of the microcirculation].

By application of thermodynamics on the theory of microcirculation in tissues one must implicate the fact that both phenomena convection and diffusion through semipermeable membranes take place in "non opened" compartments. Based on this precondition the present paper shows that the known calculations by Kedem and Katchalsky and others are insufficient in order to describe the above mentioned processes and that the reflection coefficient delta is not relevant to the real movement of molecules through capillary walls. Furthermore, the basic equation of the microcirculation is to be improved by a diffusion component in order to represent a better approximation of the exchange situation in tissues.

Capillaries↗

A new preparation of rat extensor digitorum longus muscle for intravital investigation of the microcirculation.

The extensor digitorum longus (EDL) muscle is a fast contracting muscle with 60% of Type IIB fibres at the surface. We developed a surgical procedure for exposing this surface from which the microcirculation can be visualized via intravital microscopy. From video recorded microscopic images we determined that microvascular perfusion at the surface is fairly stable for at least 5 hours. Among 7 anaesthetized rats (male Wistar), the density of perfused capillaries decreased at a rate of 4% per hr. The average velocity of red cells in perfused capillaries remained constant at 0.14 mm/s. In order to demonstrate the usefulness of the preparation we report 2 sample experiments involving muscle contraction and aging. The major advantages of EDL preparation are (1) absence of mechanical manipulation of the muscle during exposure, (2) no requirement for surface superfusion following exposure, and (3) independence of the visibility of the microcirculation from rat size and age.

Animals↗

[Effects of oxymethacil on microcirculation and neuronal impulse activity in the cat cerebral cortex in acute fosfakol poisoning].

By using the methods of vital microscopy and extracellular registration of the neuronal activity the effect of oxymethacil (OM) on microcirculation and NSA in cat brain cortex was studied after grave poisoning by organophosphate paraoxon. The rapid depression of NSA together with the pronounced disturbances of microcirculation in cortical vessels were showed after intravenous injection of paraoxon (0.8 mg/kg). The prophylactic injection of OM (5 mg/kg) induced protective effect on the studied parameters. This effect was more pronounced when OM injection was combined with the M-cholinolytic amyzyl. The present data show the reasonableness of antioxidants using for the correction of a brain functional condition damaged by organophosphates.

Acute Disease↗

[The possibility of normalizing the microcirculation using hemosorption in experimental peritonitis].

The goal of the present paper was a comparative study of microcirculation in the peritoneum, mesentery and omentum during the development of experimental peritonitis, as well as the investigation of possible correction of microcirculatory disturbances with the help of hemosorption. It has been established that different degree of microcirculatory disturbances in the tissues under study depended on the duration of peritonitis. Hemosorption recovered microcirculation to initial values, which indicated the reversibility of the disturbances.

Animals↗

[Effect of metoprolol on microcirculation and blood viscoelasticity].

In 40 patients microcirculation of skin as well as viscoelasticity of blood and plasma were investigated. 20 of them suffered from essential hypertension (group A) and were treated with metoprolol with a dosage of 50 to 200 mg per day. The rest of 20 subjects were controls (group B). In the group treated with metoprolol the values for blood viscosity were decreased in a significant manner, while skin microcirculation, blood elasticity and plasma viscosity did not show a significant difference. The results demonstrate that metoprolol is not only possible as medication in ischemic disease, but this substance can have a benefit in this indication because of its hemorheological effect.

Blood Flow Velocity↗

[The theory of microcirculation. 4: The movement of molecules through semipermeable membranes].

The movement of the molecules through semipermeable membranes does not only follow thermodynamical principles but it is also in keeping with the classical mechanics of particle movement. Hence, in presence of chemical potentials a simple diffusion at semipermeable membranes is impossible because of additional convective fluid transport, which influences the process. Reversely, every solution passing through semipermeable membranes generates a certain pattern of chemical gradients. These findings are important for the calculation of protein distributions in tissues. The current view of application of thermodynamics on microcirculation includes several misinterpretations concerning the movement of molecules through semipermeable membranes, because it does not take into consideration the special preconditions. The present paper shows, that it is necessary to reinterpretate the current concept of this field of the microcirculation.

Animals↗

[Status of microcirculation in patients with ischemic heart disease and concomitant bronchopulmonary diseases].

Microcirculation was studied by bulbar biomicroscopy in 111 coronary patients (105 males and 6 females) treated at sanatorium. Eighty-three of them exhibited concomitant bronchopulmonary impairment: chronic obstructive, chronic nonobstructive bronchitis and bronchial asthma in 40, 36 and 7 patients, respectively. The combined effect of the diseases leading to mutual aggravation has an adverse sequelae in terminal circulation, which can be managed by therapeutic impact on cardiorespiratory system. Special measures aimed at better ventilation result in microcirculatory improvement and should be included into rehabilitation programs for patients with cardiorespiratory pathology. Such patients are recommended to undergo microcirculation study which would be able to indicate the condition severity and serve a criterion of sanatorium treatment effectiveness.

Anthropometry↗

[State of lipid metabolism, platelet aggregation and microcirculation in patients with angina pectoris during plasmapheresis treatment].

The paper presents the changes found in the lipid spectrum in 48, platelet aggregation in 23 and microcirculation in 35 patients with coronary heart disease after plasmapheresis. In patients with Functional Classes III and IV angina, repeated procedures of plasmapheresis were found to result in a clinical improvement of its course in 92% of the patients and in conversion to a lower functional class of angina in 71%. Massive plasmapheresis performed by the developed methods caused a significant improvement in the lipid spectrum, blood rheology, and microcirculation, which persisted for 1 to 6 months after plasmapheresis in relation to the type of hyperlipoproteinemia.

Adult↗

[Relation between disorders of systemic microcirculation and chemotactic activity of macrophages in children with appendicular peritonitis].

As many as 58 children aged 3 to 14 years operated on for destructive forms of appendicitis complicated by diffuse peritonitis were examined for microcirculation of eye conjunctiva microvessels using biomicroscopy and for chemotactic++ activity of macrophages in an area of aseptic inflammatory reaction. The correlation analysis made it possible to reveal specific dependence of macrophagal chemotaxis on primary derangement in one or another component of the microcirculatory bed, the extent of diminution of the arteriolar, capillary and venular lumen as well as on the impairment of blood aggregation in microvessels. Detoxication therapy contributed to the improvement of microcirculation and the growth of the release of macrophages to the area of aseptic inflammatory reaction.

Adolescent↗

[Hemorrheology and microcirculation in women with pregnancy-induced hypertension].

Hemorrheologic studies were done in 100 patients with pregnancy-induced hypertension (PIH) and 100 cases of normal pregnancies. The hematocrit values in normal pregnant women and patients with mild and severe PIH were 35.96 +/- 4.92, 36.25 +/- 3.47 and 37.8 +/- 4.32 respectively. The blood viscosity was significantly increased in patients with PIH as compared with that of normal pregnant women. The study of bulbar conjunctive indicates the presence of profound disturbance of microcirculation in patients with PIH. It is suggested that the treatment of PIH should focus on vasospasm relieving, blood volume expansion, reduction of blood viscosity and improvement of microcirculation.

Blood Viscosity↗

[Status of microcirculation and rheological properties of blood in patients with cerebral circulatory disorders].

Microcirculation and rheological properties of blood were investigated over time on the basis of the findings of biomicroscopy of the bulbar conjunctiva in 61 patients with different stages of circulatory encephalopathy in the presence of arterial hypertension and atherosclerosis. Rheological properties of blood were changed at all stages of disease. Correlations between the ability of erythrocytes to aggregation and the degree of their intravascular aggregation by the findings of biomicroscopy of the bulbar conjunctiva were not found. The importance of investigation of the intravascular aggregation of erythrocytes and theological properties of blood for assessment of the cerebral vascular microcirculation, control of therapy, and verification of some aspects of the mechanism of action of various drugs was shown.

Adult↗

The influence of reactive hyperemia and leg dependency on skin microcirculation in patients with peripheral arterial occlusive disease (PAOD), with and without diabetes.

The increase in venous pressure during leg dependency causes a vasoconstriction of the distal vascular bed in healthy subjects, which is due to the so-called veno-arteriolar reflex. The aim of the present study was to investigate if this reflex is disturbed in patients with severe peripheral arterial occlusive disease (PAOD), with and without diabetes. The total skin microcirculation during rest and postocclusive reactive hyperemia (PRH) after a three minute arterial occlusion at the ankle was studied by laser Doppler (LD) fluxmetry. The LD probe was attached to the dorsal region of the foot in 10 legs of healthy control subjects, patients with PAOD, and patients with PAOD and diabetes respectively. No vasoconstriction was seen in the PAOD group when the leg was moved from the supine to the dependent position. The PRH response was also significantly (p less than 0.05-0.01) impaired compared to the controls in both positions. The diabetic PAOD patients had an almost normal reactivity in spite of an equally reduced arterial circulation as the non-diabetic patients. The results show that patients with PAOD have a significantly disturbed reactivity of the skin microcirculation in the ischemic foot, while the reactivity in diabetic PAOD patients is almost normal.

Aged↗