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[Disorders of microcirculation in subarachnoid hemorrhage and intracerebral hemorrhage].

The pathophysiological notions of hemodilution treatment of ischemic seizures with plasma expanders indicates the significance of microcirculation. Microcirculation disorders arise from the interrelations of hemodynamic, vascular, and hemorrheologic factors. It seems that hemodilution with hydroxyethyl starch reduces peripheral microcirculation disorders, thus inhibiting the development of cerebral edema. In the case of subarachnoid hemorrhage, the hemorrheologic factors deteriorate less severely when given antifibrinolytic treatment with Aprotinin. Simultaneous hemodilution with hydroxyethyl starch can counterbalance the already existing changes.

Blood Coagulation Tests

[Intraoperative contact biomicroscopy as a method of assessing disorders of microcirculation in ileus of the small intestine].

The article describes an experience with visual microscopic assessment of disturbances of microcirculation in the small intestine in various forms of acute ileus. The assessment of microcirculation in the small intestine wall with the help of a microscope facilitates more objective establishment of indications for the resection of ischemic portions and drainage of the intestine by intubation. This method of direct assessment of microcirculation disturbances in the intestine is a promising one and requires further development.

Adult

Effects of endotoxin on the splenic microcirculation and its cellularity.

This report describes the effects of endotoxin treatment on the intrasplenic microcirculation and cellularity in rats. Four and 16 h after a single intravenous injection of endotoxin (2 mg/100g body weight), altered intrasplenic microcirculation was observed. The open circulation was reduced from 97% in the control rats to 79% in the endotoxin treated rats, while the closed circulation increased from 3% in the controls to 21% in the endotoxin treated rats. Such changes in the splenic microcirculation may be partly due to the presence of fibrin and the pooling of polymorphonuclear leukocytes and red blood cells in the red pulp. The most apparent cellular changes seen in the white pulp of endotoxin treated rats 16 h after endotoxin injection are the disappearance of lymphocytes from the periarterial lymphatic sheath and the appearance of many giant macrophages within the white pulp. The giant macrophages contain lymphocytes undergoing various stages of degradation. This suggests that the lymphocytes may be injured by endotoxin treatment and are subsequently phagocytosed by macrophages.

Animals

Effect of theophylline treatment on the functional hyperaemic and hypoxic responses of cerebrocortical microcirculation.

The purpose of the present study was to elucidate the importance of extracellular adenosine (ADO) in the regulation of cerebrocortical microcirculation during rest, hypoxia, and brain activation. Cerebrocortical microcirculation and fluorescence of reduced nicotinamide adenine dinucleotide (NADH) were measured by surface fluororeflectometry through a cranial window. Arterial hypoxia and brain activation were produced by respirating the animals with a gas mixture containing 6-7% O2 and by injecting 4-6 mg/kg metrazol into the lingual artery, respectively. These reactions were used as test before and after theophylline (THEO) treatment. In some of the experiments only the cortical area beneath the cranial window was treated with THEO (10(-4) M), in others 2 X 10(-4) mol/kg THEO was injected intraperitoneally. Potency of THEO in antagonizing the cerebral blood flow (CBF) increasing effect of topically applied ADO was also tested. It was found that superfusion of the brain cortex with artificial cerebrospinal fluid (mock CSF) containing 10(-4) M THEO does not alter resting CBF, but inhibits the CBF increasing effect of 10(-6) M and 10(-5) M ADO by approximately 70% and 40%, respectively. Intraperitoneally injected THEO increased CBF by approximately 60%, which has been attributed mostly to its action on the systemic circulation. Under control conditions, arterial hypoxia and epileptic seizures increased CBF by approximately 150% and 300%, respectively. Since neither topical nor systemic THEO treatment altered the vasodilatory and CBF increasing potency of arterial hypoxia and attenuated these effects of epilepsy slightly, it was concluded that extracellular ADO is not a critical factor in the regulation of cerebrocortical microcirculation.

Adenosine

[Functional relations between microcirculation and oxygen supply (physiologic peculiarities in polarographic pO2 measurement in tissue)].

The measurement of the partial pressure of oxygen in the tissue is a method increasingly used in experiment and clinic, the technical prerequisites for this having been created by means of the development of polarographic measuring techniques (surface or scarifier-electrodes). The pO2-measurement of the tissue renders possible independent conclusions to the relations of microcirculation of the organs examined and to the effectiveness of the blood supply of the tissue as well as its homogeneity and nutritive achievement for the cellular metabolism. On the basis of the intravital microscopic findings in connection with perivascular pO2-measurement the pathophysiological peculiarities of this measuring method are discussed. The physiologically involved temporary and spatial inhomogeneities of the peripheral blood supply limit, however, the generalization of locally (approximately 200-300 microns3 measuring area) established oxygen values for diagnostics and therapy control. For the measurement an intact microcirculation and the simultaneous registration in several measuring places is necessary. Then the following informations may be obtained, e.g.: control of the exact dosage of an inspiratory O2-supply--control of the volume balance--control of the haemodynamic effect of drugs on the microcirculation.

Capillaries

[Changes in the blood microcirculation in the mouth mucosa in experimental stomatitis].

Aphthous lesions in the oral mucosa (OM) were simulated in dog experiments by ligation of the common bile duct. In one of the experimental groups the beta-adrenoblocker propranolol was administered 30 min before surgery. Two hours after surgery the animals manifested changes in blood microcirculation of the OM. In animals treated with propranolol, the characteristics of blood microcirculation remained within normal. It is concluded that the development of aphthous lesions is preceded by functional disorders of blood microcirculation in the OM which are probably related to alterations in the neurovascular system.

Animals

[State of microcirculation in various zones of the heart in myocardial infarct complicated by congestive circulatory insufficiency].

A definite correlative connection has been revealed between the clinical course of myocardial infarction, the extent of affection of the heart muscle, the severity of the atherosclerotic process in the coronary arteries, and the condition of microcirculation in different zones of the heart. The severest affections of the heart muscle, stenosing coronarosclerosis and disorders of microcirculation in different zones of the heart were encountered in patients with myocardial infarction marked by a recurrent course and complicated by cardiogenic shock or congestive circulatory insufficiency. It is shown that the character of changes in microcirculation determines to a great measure the later condition of the structure and function of the myocardial muscle cell in areas near and remote from the infarction.

Adult

Laser-induced endothelial damage inhibits endothelium-dependent relaxation in the cerebral microcirculation of the mouse.

This study demonstrates endothelium-dependent relaxation in the surface arterioles of the brain. A helium-neon laser was used to injure endothelium in situ following i.v. injection of Evans blue dye, which sensitizes the bed to the laser. Areas 18 or 36 micron in diameter were injured and no longer relaxed to either 1 ml of acetylcholine chloride or bradykinin triacetate, 80 micrograms/ml delivered for 60 seconds. Dilations to sodium nitroprusside (30 micrograms/ml) were unaffected. Normal responses to nitroprusside, plus electron microscopy, established that vascular smooth muscle was uninjured. Endothelium-dependent relaxation was impaired when only minor ultrastructural damage was present. Dilation was inhibited downstream and upstream as far as 80 micron from the center of the laser beam. This suggests a spread of endothelium injury around the site of laser impact. However, inhibition was somewhat more marked downstream than upstream, implying that a portion of the downstream response was dependent on a substance released from an upstream site. To date, very few studies have reported endothelium-dependent relaxation in vivo, especially in the microcirculation. The present study accomplishes this. Moreover, in contrast to in vitro observations of endothelium-dependent relaxation in large vessels, the in vivo elimination of endothelium-dependent relaxation in the microcirculation required neither removal of endothelium nor injury to large numbers of endothelium cells. Since endothelium-dependent relaxation in the microcirculation has now been demonstrated using three different techniques to injure endothelium, it is reasonable to conclude that the phenomenon is real.

Acetylcholine

Abnormalities of the coronary microcirculation in acute murine Chagas' disease.

Chronic Chagasic heart disease has many features characteristic of other congestive cardiomyopathies, including ventricular and atrial chamber enlargement, hypertrophy, focal scarring, and mural thrombi. Histologically, there is often lymphocytic inflammation, spotty necrosis, and few parasites. Although immunologic mechanisms have been invoked to explain the development of myocardial degeneration, there have been suggestions that the focal alterations in the heart are secondary to abnormalities of the coronary microcirculation. Based on work from our laboratories which has demonstrated microvascular hyperreactivity in several other models of congestive cardiomyopathy, we investigated whether the cardiac microcirculation of mice acutely infected with Trypanosoma cruzi was also abnormal. We perfused animals at 15-17 days post-infection with silicone rubber which fills the arterioles, capillaries, and venules of the beating heart. After clearing the tissue, we observed numerous areas of focal vascular constriction, microaneurysm formation, dilatation, and proliferation of microvessels which were not present in control animals. These lesions were similar to those we have observed in other congestive cardiomyopathies. Since at this stage of infection there is minimal cardiac degeneration or fibrosis, the presence of these vascular lesions even early in Chagas' disease, may be significant for the pathogenesis of focal myocardial damage. These observations during acute infection provide additional support for the suggestions of others that the myocardial microcirculation is abnormal in Chagas' disease.

Aneurysm

Bone marrow necrosis. acute microcirculation failure in myelomonocytic leukemia.

We saw bone marrow necrosis in a case of acute myelomonocytic leukemia. The diagnosis was made during the patinet's life, and the bone marrow microcirculation was studied immediately postmortem. Histology and injection of the bone marrow arteries showed an acute microcirculation failure. The pathogenesis and possible relationship with soluble immune complexes was studied.

Adult

A filtration model for study of leukocyte transit in the microcirculation.

In order to study characteristics of leukocytes which would be important determinants of their flow in the microcirculation, a model system was tested which utilizes in vitro filtration of leukocytes. Normal human peripheral blood leukocytes (85-90% granulocytes) were studied with filters with uniform 8 mum pore size. Studies were performed to determine the effects of EDTA, temperature, hydrostatic pressure, pH, and osmolarity on filtration. Filterability was optimal at 0.2% EDTA, 10 cm hydrostatic pressure, neutral pH, isotonicity, and at room temperature. Filtration was slowed greatly at leukocyte concentrations exceeding 25 X 10(9)/liter. When leukocyte membranes were altered by formalin fixation, filtration slowed greatly, indicating that deformability is an important determinant of flow through small orifices. When mixtures of erythrocytes and leukocytes were filtered, there was a paradoxically enhanced transit of leukocytes compared to filtration of leukocytes alone, indicating interactions between these cells which alter flow. These studies serve to characterize this model system which can be used to study the contribution to flow in the microcirculation of both normal and pathological leukocytes.

Adult

Effect of 16,16-dimethyl prostaglandin E2 on oxygen uptake and microcirculation in the perfused rat liver.

Previous work demonstrated that collagen deposition in the liver of rats fed a nutritionally deficient diet for 3 to 4 months was diminished markedly by 16,16-dimethyl prostaglandin E2 treatment. In this study, rats were fed a high-fat diet or a high-fat diet deficient in lipotropes for 2 to 4 weeks prior to liver perfusion. Rates of O2 uptake by the liver were not changed by dietary manipulation. Infusion of 16,16-dimethyl prostaglandin E2 (10 microM), however, decreased O2 uptake by the whole organ by 20 to 40% in both groups. O2 tension was measured at the liver surface with a miniature O2 electrode placed alternatively on periportal and pericentral regions of the liver lobule. Mean O2 tensions in both periportal and pericentral regions were reduced 2- to 3-fold during the infusion of 16,16-dimethyl prostaglandin E2 suggesting an action on the microcirculation. This hypothesis was supported by the observation that fluorescein isothiocyanate-dextran fluorescence detected from the liver surface as well as hepatic vascular volume determined by dye dilution techniques were decreased 30 to 50% by 16,16-dimethyl prostaglandin E2. In addition, 16,16-dimethyl prostaglandin E2 increased portal pressure by about 10 mm Hg in a reversible manner. Thus, it is concluded that pharmacological levels of 16,16-dimethyl prostaglandin E2 affects the microcirculation dramatically in the isolated perfused liver.

16,16-Dimethylprostaglandin E2

Lethal deformation of cancer cells in the microcirculation: a potential rate regulator of hematogenous metastasis.

The hypothesis has been advanced that deformation-induced lethal mechanical trauma, resulting in surface-membrane rupture, is inflicted on circulating cancer cells trapped in the microcirculation, and that this rapid cell-killing mechanism is a potentially important rate regulator for hematogenous metastasis. We describe and discuss an in vivo test of this hypothesis. Vital fluorescence microscopy was performed on the microcirculation of cremaster muscle preparations in mice, following retrograde injections into the femoral artery of acridine orange-stained sarcoma cells. Cancer cells having mean diameters of 16.5 microns in suspension, were deformed from spheres into cylinders having a mean length of 53 microns, in 7-microns diameter capillaries. Most of these cells were dead several minutes after injection. It was estimated that sphere-to-cylinder shape-transitions of this magnitude required an average increase of 52% in apparent cell surface area. Evidence is presented that most of this apparent increase was achieved by non-lethal surface "unfolding", utilizing membrane "excess". That cancer-cell deformation of the magnitude observed in vivo is the direct cause of lethal, surface-membrane rupture was indicated by the observed loss of membrane integrity in cells deformed from spherical to cylindrical shape in vitro, by aspiration into micropipettes of capillary dimensions. The experimental observations are therefore consistent with the hypothesis.

Animals

The effect of acute denervation on the microcirculation of skeletal muscle: rat cremaster model.

Although tissue is denervated during replantation of a severed part, tissue transfer, or muscle transplantation, there are few studies concerning the effects of acute denervation on muscle microcirculation. We have described a surgical procedure that totally denervates the rat cremaster muscle. Histological examination of the denervated tissue has given convincing evidence of nerve degeneration and skeletal muscle atrophy, accompanied by electrophysiological evidence of total denervation. The diameters of each component of the microcirculation were measured before and after denervation. Arterioles and arteries ranging in size from 10 to 70 microns in diameter were found to increase significantly in size immediately after acute denervation. Larger arteries and veins did not undergo significant diametrical increases. These findings suggest that total acute denervation significantly increases the diameter of small arteries and arterioles, thereby decreasing the resistance in the arterial bed and increasing blood flow. Since this phenomenon is of limited duration (20 min), it would appear to be ineffective in enhancing reperfusion and oxygenation at the time of reattachment of amputated parts or during vascularized tissue transfers, until methods of prolonging it for several hours or more are found.

Animals

In situ testing of CO2 laser on dental pulp function: effects on microcirculation.

The effect of CO2 laser irradiation on pulpal microcirculation was studied in cat canines. The enamel surfaces of 4 teeth were exposed with energy densities of 304-1440J/cm2, using either a handpiece or a microslad, with a focal spot of 0.21mm and 0.33mm respectively. Pulpal blood flow (PBF) before and following lasing was recorded through the intact tooth surface by a laser Doppler flowmeter. CO2 laser irradiation caused an increase in PBF, which was immediate and transient. The PBF increase was higher in a large pulp than in a small pulp, and it was inversely related to the focal spot size. These findings confirm that the dental pulp is thermally affected by CO2 lasing of the tooth surface, however, without extensive pulp coagulation. It is concluded that the effects of laser irradiation on the pulpal microcirculation may be studied in situ by means of the presented methodology.

Animals

Effect of ionizing radiation on liver microcirculation and oxygenation.

Platelet aggregation and adhesiveness, as well as TPO2 responses to hypoxia were measured as microcirculation parameters in beagle dogs subject to Co60 ionizing radiation to a dose of 4600 rads in 5 weeks. Simultaneously, changes in blood chemistry and coagulation were also determined. Marked changes in all studied parameters in the post radiation period lead to the conclusion that radiation liver damage is at least in part mediated through microcirculation disturbances.

Animals

Hepatic microcirculation in Zucker fatty rats.

We have developed a microscopic analyzing system for studying in vivo hepatic microcirculation, and measured the sinusoidal erythrocyte flow velocity simultaneously in the various sinusoids. With this system and organ reflectance spectrophotometry, the pathophysiological role of microcirculation and of energy metabolism in Zucker fatty rats were studied. The results were as follows: The erythrocyte flow velocity in the predominant sinusoids in the fatty rats was similar to that of the control rats, but the intersinusoidal erythrocyte flow was undetected in the fatty liver. Index of regional hepatic blood volume, regional hepatic blood flow and oxygen saturation of Hb decreased significantly in the fatty rats. The estimated in vivo oxygen consumption was not changed in the fatty liver. From these data, it is concluded that in Zucker fatty rats a marked fatty infiltration causes a decreased hepatic tissue blood flow and volume, but relatively homogeneous erythrocyte flow with an increased extraction of oxygen compensated the decreased vascular beds and maintained normal energy metabolism.

Animals

Prevention of ionizing radiation-induced liver microcirculation changes by the use of flow improvers.

Platelet aggregation and adhesiveness, as well as TpO2 responses to hypoxia were measured as microcirculation parameters in beagle dogs subject to Co60 ionizing radiation to a dose of 4600 rads in 5 weeks. Simultaneously, changes in blood chemistry and coagulation were also determined. Marked changes in all studied parameters in the post radiation period lead to the conclusion that the radiation liver damage, which is at least in part mediated through microcirculation disturbances, can be prevented with the flow improver, Rheomacrodex.

Animals