Clinical Hemorheology and Microcirculation - Volume 2, issue 5-6

Authors: Copley, Alfred L.

Article Type: Editorial

DOI: 10.3233/CH-1982-25-601

Citation: Clinical Hemorheology and Microcirculation, vol. 2, no. 5-6, pp. vii-vii, 1982

Authors: Witte, Siegfried

Article Type: Editorial

DOI: 10.3233/CH-1982-25-602

Citation: Clinical Hemorheology and Microcirculation, vol. 2, no. 5-6, pp. ix-x, 1982

Authors: Witte, S.

Article Type: Other

DOI: 10.3233/CH-1982-25-603

Citation: Clinical Hemorheology and Microcirculation, vol. 2, no. 5-6, pp. 413-413, 1982

Authors: Meessen, Hubert

Article Type: Research Article

Keywords: Diapedesis, terminale Strombahn, histion, endothelium

DOI: 10.3233/CH-1982-25-604

Citation: Clinical Hemorheology and Microcirculation, vol. 2, no. 5-6, pp. 415-423, 1982

Authors: Hammersen, F. | Hammersen, E.

Article Type: Research Article

Abstract: (I) The blood capillary endothelial cell (EC): Three different structures play a more or less decisive rôle in capillary permeability characteristics: (1) a delicate endothelial layer of glycoproteic nature, (2) intracytoplasmic vesicles and/or channels of different stereological configurations with a max. inner diameter of 50 nm, and (3) interendothelial clefts 15-20 nm wide of variable length and course, fitted with attachment decives of variant fine structure. (II) The interstitial space (ISS): To evaluate the barrier functions of this compartment with the limited arsenal of morphological techniques is extremely difficult, and therefore the results are controversial. Using electron-dense tracers of …variant molecular seizes, the very first component of the ISS directly beyond the endothelial cells, i.e. their basal lamina, does not seem to function as a general, ubiquitous sieve for molecules up to a seize of 5 nm. Caution, however, is emphasized against data obtained and conclusions drawn from model experiments performed with a very special, yet frequently employed representative of endothelial basal laminae, i.e. the glomerular basement membrane. The adjoining interstitial space proper (ISS) consists of three major components: (1) a fluid phase, (2) a phase of dissolved macromolecules, and (3) the matrix which is composed of long chain molecules of fibrous proteins (e.g. collagen) and glucosaminoglycans (mucopolysaccharides). While the first two of these constituents are more or less beyond the reach of any structural analysis, the third component can be studied more closely with both histochemical techniques and electron microscopy to elucidate its chemical and structural composition. Not this, however is the objective of the present contribution, but the barrier functions of the ISS, which depend to a variant extent on all its components. Off these it is the matrix again which allows to demonstrate at an ultramicroscopic level at least one of its permeability characteristics, namely the phenomenon of ‘exclusion’. Another proposition held over more recent years emphasized the regular occurence of nonendothelialized, preformed ‘tissue channels’ which should serve as ‘prelymphatics’ of variable length and diameter in almost every tissue and organ. The methods, between, however, by which the existence of such ‘channels’ has been proven are open for severe criticism due to the many artifacts involved in the techniques employed. At this stage it seems, therefore, to be premature to correlate already these structurally defined ‘channels’ with those postulated to exist on the grounds of permeability data and calculations. (III) The endothelium of the initial (terminal) lymphatics: As compared to the blood capillary endothelial cells, lymphatic endothelium appears to be more uniform with less topical spezializations. It differs from blood capillary ECs in several ways: (1) It is extremely thin over large areas except its nucleated portion. (2) Micropinocytic vesicles are less numerous and most of them tend to form lysosomal vacuoles instead of ferrying materials across the endothelial barrier. (3) The interendothelial clefts vary in width and they are often loosely arranged with no or less elaborate attachment decives. Open gaps of up to several microns width are regularly encountered. (4) The basement membrane is discontinous and ‘anchoring filaments’ insert in a densely staining substance of the abluminal endothelial plasmalemma. They extend into the surrounding connective tissue and they exert tension on the lymphatic wall thus stabilizing the vessel, keeping its lumen open and under certain conditions they may even pull adjoining ECs apart. Show more

Keywords: Endothelial cell, ultrastructure, interstitial space, initial lymphatic, vesicular transport

DOI: 10.3233/CH-1982-25-605

Citation: Clinical Hemorheology and Microcirculation, vol. 2, no. 5-6, pp. 425-440, 1982

Authors: Hörmann, Helmut

Article Type: Research Article

Abstract: Connective tissue is a complex system consisting of cells, fibers and interstitial mucoproteins and glycoproteins. Among fibers collagen is the most important. Several genetically distinct types of this structural protein are known which are specific for various tissues. Their synthesis includes numerous steps beginning with the formation of procollagen peptide chains which subsequently are modified by hydroxylation and glycosylation and are twisted to triple-helical structures. Removal of terminal globular domains is required for assembly of monomers to fibrils which later on are stabilized by covalent cross-linking. Several inherited diseases like dermatosparaxis or special forms of Ehlers-Danlos syndrom are due to …the inability of performing one of these steps. In addition, incomplete processing of collagen can be the result of malnutrition e.g. lack of ascorbic acid, copper deficiency or lathyrogens in the food. Far more important among connective tissue diseases is an excess of fiber formation in soft tissues. Fibrosis of liver and lung, probably, is not the result of an increased collagen synthesis but of an increased conversion of soluble collagen precursors to fibrils. Unless fibrils are formed the soluble collagen derivatives are removed by proteolytic digestion. Regulation of fibrillogenesis, however, is little understood and, evidently, involves the participation of glycosaminoglycans and glycoproteins. One model assumes that collagen precursors deposit on preformed fibronectin fibrils constituting the pericellular matrix of fibroblasts and other adherent cells. The expression of this pericellular matrix, on the other hand, appears to be regulated by glycosaminoglycans on the cell surface and the near environment. It varies with the cell cycle, the cell density and the proliferation activity of the cells and is influenced by several drugs. Following establishment of collagen fibers the fibronectin guide-lines, evidently, are removed. The cell environment also influences the type of collagen expressed. Chondrocytes producing collagen type II, under special conditions, convert to fibroblast-like cells synthesizing type I and type III. Simultaneously the kind of glycosaminoglycans produced is changed. Show more

Keywords: Connective tissue, collagen, glycosaminoglycan, fibroblast, fibronectin

DOI: 10.3233/CH-1982-25-606

Citation: Clinical Hemorheology and Microcirculation, vol. 2, no. 5-6, pp. 441-451, 1982

Authors: Lindner, J. | Lindner, Ch.

Article Type: Research Article

Abstract: The pathology of connective tissue is demonstrated by the most important example: the inflammation, summarizing the basic processes of pathological reactions of connective tissues on the several irritations and injuries. Comparative morphological and biochemical methods, employed on the same material as far as possible, allow a better insight into and investigation of the single stages of inflammation, which start very fast. They have been localized qualitatively and assayed quantitatively, esp. the processes occuring immediately after the start of inflammation as the several steps of the disturbed regulatory equilibrium between catabolism and anabolism in the involved connective tissue. The …primary increase of the catabolism at the beginning of inflammation is followed almost immediately by an increased anabolism of all 3 components of the vascularized connective tissue, i.e. the substrate of inflammation: cells, ground substance and fibres. Thus their turnover is remarkably increased in inflammation. The single phases of inflammation are regarded in relation to each other and summarized: the cell injuries, endothelial cells included, the several stages of disturbed blood flow (prestasis, stasis and poststasis), the enhanced permeability and their consequences (swelling, dissolution, degradation etc.), exudation and emigration, sticking processes and chemotaxis, mediators and their effects, granulocytes, lymphocytes, monocytes and macrophages, their functions, the immunological responses included, but esp. the processes of pinocytosis and phagocytosis, the whole degradation and breakdown of phlogistics as well as of the components of the injured, inflamed and damaged connective tissue. Its replacement is achieved by the new formation of capillarized granulation tissue, depending on the intensity and duration of the inflammation. So, finally scars can result, with reduction of capillaries, cells and ground substance. Then the collagen content prevails. The catabolic and anabolic processes during inflammation are regarded in their feedback relations, esp. of the proteoglycans and collagen, their several heterogeneities, their interrelations, interactions and interdependencies included. They are also described as main processes of the disturbed equilibrium of connective tissues, i.e.: the basic and fundamental processes of the “pathology of Connective Tissues”. Than many degenerative lesions are the final results of some of these main and general steps of connective tissue reactions. The disturbances of these several relations and phases during inflammation by drugs are discussed finally. The influences of the most common antiphlogistic agents on inflammation intervene in the various mechanisms of these turnover alterations of the 3 main components (cell, proteoglycans and collagen), i.e. as a rule, not only in one process. Often cell proliferations, lysosomal degradations, syntheses of catabolic and/or anabolic enzymes and of the intracellular macromolecular substances (= the differentiation products of connective tissue cells) can be influenced by application of one antiphlogistic drug. Since the extent and duration of inflammations strongly depend on the extent of degradation and/or of the extent of enhanced catabolism and anabolism during the start of inflammation, it is emphasized to influence inflammations as early as possible, best by previous antiphlogistic drug administrations. This is practicable in many cases of inflammation in human medicine. So the most important basic subjects of the “Pathology of Connective Tissue” are demonstrated and discussed from the theoretical and clinical point of view. Show more

Keywords: Connective tissue, inflammation, stasis, permeability, mediator substances, basement membrane

DOI: 10.3233/CH-1982-25-607

Citation: Clinical Hemorheology and Microcirculation, vol. 2, no. 5-6, pp. 453-495, 1982

Authors: Silberberg, A.

Article Type: Research Article

Abstract: Mechanical and chemical communication between cells depends upon the structure and biophysical character of the connective tissue space. From the point of view of the microcirculation (mainly its extravascular part and lymph formation) the permeability, selective and unselective, of the connective tissue matrix is of most obvious interest. It turns out, however, that the mechanical properties of the tissue are of no less importance, since they help to determine the gradients in chemical potential which exist between the blood stream and the tissue interstitium on the one hand and the interstitium and the lymph collecting system on the other. These …biophysical features of the connective tissue space, the transport and the mechanical properties, depend upon connective tissue structure and composition. It is convenient to divide the materials composing connective tissue into two groups: Immobilized, or essentially immobilized, components and diffusible components. The former involve mainly the fiber network system. This provides the mechanical integrity both of the connective tissue matrix and of the cells which are embedded in it or are attached to it. The fiber system is composed mainly of highly organized collagen fibers but also involves fibers of elastin and a network of structural glycoprotein. The ultimate strength of the tissue is that of the collagen system. The mechanical response to smaller deformation, however, is determined both by collagen fiber bending and elastin fiber rubber-like extensibility. The structural glycoprotein seems to have a modifying role. While these components are truly immobilized they constitute only a minority volume fraction in the tissue space. The voids are filled with diffusible species (mainly water), but also with a system of extremely high molecular weight, hydrophilic proteoglycans/hyaluronic acid associates. The chains of these have the tendency to coil freely through space being charged and largely carbohydrate in nature. Their large size traps them in the fiber environment though they do not really seem to be linked to the fiber system, even by secondary chemical interactions. Because of their intimate contact with water and of the charges they carry, they strongly affect the chemical potential of water and thus determine the tendency of tissue to absorb water. The extent of swelling attained is limited by a pressure rise imposed by mechanical stress induced in the fiber network. In this respect the connective tissue space is behaving like any gel-like system. Of interest here is that the mechanical and concentration effects on water chemical potential are physically separated and arise in two distinctly different immobilized structural components. The diffusible species, which besides water fill the interstitium can also be graded into roughly two groups: A group of low molecular weight components, mainly sodium chloride, which cross the blood/tissue barrier, essentially without hindrance, along with water. A group of high molecular weight species, mainly serum albumin whose passage is severely restricted and which occur, therefore, in the interstitium at a concentration very different to their concentration in blood. The chemical potential of water in tissues thus differs from that in blood because of this concentration difference, because of the presence of the proteoglycan/hyaluronic acid system and because of a difference in hydrostatic pressure. Since the connective tissue space can support only small gradients (due to much faster diffusion than convection of the diffusible species) and the chemical potential of water in blood decreases as the hydrostatic pressure drops from the arterial to the venous end of the microcirculation, the driving force on water will be outward at the arterial end and inward at the venous end. This is the basis of the Starling balance. In addition, water (and diffusible protein) can be cleared from the tissue spaces as lymph. This is necessary since protein driving forces do not permit a direct return to the blood stream by reabsorption. Show more

Keywords: Connective tissue, collagen, proteoglycan, lymph, diffusion

DOI: 10.3233/CH-1982-25-608

Citation: Clinical Hemorheology and Microcirculation, vol. 2, no. 5-6, pp. 497-508, 1982

Authors: Silberberg, A.

Article Type: Other

DOI: 10.3233/CH-1982-25-609

Citation: Clinical Hemorheology and Microcirculation, vol. 2, no. 5-6, pp. 509-509, 1982

Authors: Lee-Kelland, S. | Floyer, M.A.

Article Type: Research Article

Abstract: There are two pressures in the tissues which affect the flow of fluid across the capillary wall: the interstitial hydrostatic and oncotic pressures. The methods used to measure these pressures have been the subject of controversy and this has led to some doubt about the correct values. The manometer described below was designed to minimise the problem of scar tissue formation, slow equilibration and inflammation encountered in other techniques. Two types of membrane are used. The first is a large pore membrane which allows the measurement of the sum of the hydrostatic pressure and the pressure due to the …interstitial matrix. The second is a small pore membrane which permits the determination of the sum of the hydrostatic and oncotic pressures in the interstitium. The aim of the manometer design is to achieve extremely rapid measurement of pressures. Equilibration can usually be obtained in 1–2 minutes, although with some membranes as little as 30 seconds is required. When the subcutaneous fascia of the ventral abdomen of the rat is rapidly exposed and the membranes place on it, the following pressures are found. The large pore membrane gives a mean pressure of −1.85 cmH2 O (S.D. 0.7, n = 20) in the superficial fascia and a mean pressure of −1.85 cmH2 O (S.D. 0.8, n = 7) on the fibrous tissue overlying the abdominal muscles. The small pore membrane gives a mean pressure of −12.53 cmH2 O (S.D. 2.57, n = 13) on the superficial fascia and the same pressure on the fibrous tissue overlying the muscles. Subtraction of the pressure found with the large pore membranes from that found with the small pore membranes gives the oncotic pressure due to plasma proteins in the tissues. This pressure was −10.7 cmH2 O. Show more

Keywords: Tissue pressure, interstitial space, oncotic pressure, oncometer, inflammation

DOI: 10.3233/CH-1982-25-610

Citation: Clinical Hemorheology and Microcirculation, vol. 2, no. 5-6, pp. 511-522, 1982

Authors: Born, G.V.R. | Kratzer, M.A.A.

Article Type: Research Article

Abstract: Circulating platelets show no tendency to adhere to the walls of normal blood vessels but do so rapidly and specifically where insides of vessels are damaged by injury or disease except, apparently, in capillaries. Adhesion is followed by aggregation of platelets except again in the smallest and also in the largest vessels, i.e. in the aorta. Such platelet aggregation is responsible for primary haemostasis and arterial, ego coronary thrombosis as well as for obstructive deposits in extracorporeal circulations. Measurements of the haemodynamic forces required to activate platelets, directly indicate that the flow abnormalities caused by atherosclerotic lesions in vivo …cannot account for local activation of circulating platelets. On the other hand, there is considerable evidence for the indirect activation of platelets by the operation of haemodynamical forces on the red cells. High collision frequencies between red cells and platelets do not by themselves cause the latter to aggregate. It seems that the activation of platelets by erythrocytes depends on their providing a chemical agent, presumably ADP. Recent experimental and clinical evidence suggests that the activation of platelets by erythrocytes may be diminished by drugs. Chlorpromazine and similar drugs, in concentrations which stabilise the erythrocyte membrane against haemolysis but are too low to affect platelets directly, increase the “bleeding time” both experimentally and clinically under conditions in which this time is determined by the reactivity of platelets and in which the drug does not inhibit platelet aggregation directly. Show more

Keywords: Platelet aggregation, bleeding time, platelet adhesion, ADP

DOI: 10.3233/CH-1982-25-611

Citation: Clinical Hemorheology and Microcirculation, vol. 2, no. 5-6, pp. 523-533, 1982

Authors: Crone, C.

Article Type: Research Article

Abstract: With the newly developed technique for studying solute transport across capillary walls in single capillarries by means of microelectrodes (Crone et al. 1978, Crone and Christensen, 1981) it has become possible to distinguish between diffusion across the capillary wall and diffusion in the interstitium. When a high potassium solution is placed within a closed capillary segment in the frog’s mesentery an outward diffusion starts immediately. With potassium-sensitive microelectrodes within and just outside the capillary it is possible to study the emptying of excess potassium from the closed segment. There is a clear jump in concentration across the capillary wall, …reflecting the diffusion hindrance in the endothelium and clearly showing that diffusion in the interstitium is faster than in the wall. The diffusion coefficient of potassium in the interstitium is about 40 % of the free diffusion coefficient and thus the extravascular tissue has a delaying influence upon the spread of solutes. It is possible that in fenestrated capillaries transport across the capillary wall is so fast that the diffusion velocity in the interstitium becomes rate-limiting, but it is not very likely. The principal reason for the diffusion delay in the capillary wall is the presence of endothelial cells, reducing the available surface area for passage of hydrophilic solutes to about 1/10.000 of the total surface area. Although the investigations have dealt with small solutes, it is likely that the conclusions also hold for macromolecules. Show more

Keywords: Capillary permeability, interstitium, ion-sensitive microelectrode, endothelium, diffusion hindrance

DOI: 10.3233/CH-1982-25-612

Citation: Clinical Hemorheology and Microcirculation, vol. 2, no. 5-6, pp. 535-546, 1982

Authors: Rutili, Gianfranco | Arfors, Karl-Erik

Article Type: Research Article

Abstract: The relationship between interstitial fluid, initial lymphatics and collecting lymphatics was investigated in the subcutaneous tissue of rabbits. 24 hours after intravascular injection of FITC-dextran (FITC-dx) of M w ¯ 145 , 000 plasma, interstitial fluid and lymph from initial and collecting lymphatics were collected using a micropuncture technique and analysed for the content of FITC-dx and endogenous proteins. The fluid concentration of interstitium, initial and collecting lymphatics was found not to be statistically different from each other. These findings support previous studies demonstrating high permeability of the lymphatic endothelium to macromolecules. The hypothesis …of a concentrating mechanism at the initial lymphatics was not supported by the present results. Integrated with previous data on the distribution volume of macromolecules in the same tissue, the present results suggest that the fluid flow in the interstitium takes place through the fluid phase only. Show more

Keywords: Interstitial fluid, lymph, macromolecules, FITC-dextran, permeability

DOI: 10.3233/CH-1982-25-613

Citation: Clinical Hemorheology and Microcirculation, vol. 2, no. 5-6, pp. 547-560, 1982

Authors: Witte, S.

Article Type: Research Article

Abstract: As an experimental model for capillary permeability we investigated the behavior of fluorescent labeled proteins by means of vital fluorescence microscopy of the rat mesentery exposed into a transparent superfused chamber. Fluorescent labeled proteins injected intravenously pass through the vascular wall, preferably at the venous site of the microvasculature, spread into the perivascular interstitial tissue and appear eventually in the regional lymph vessels. By various experimentally induced changes of the coagulation system we found alterations of the permeability processes. In states of hypocoaguability the passages of proteins through the vascular wall and within the interstitial space are augmented. Proteins are …transported more rapidly and in greater amounts from the blood into the perivascular tissue. An anatomico-topographical affinity of coagulation factors to the vessel wall of the microcirculation has been investigated by the same technique injecting fluorescent labeled coagulation factors. We found a peculiar accumulation of fibrinogen, at the vascular wall, especially at the inner lining of venules, prefering the interendothelial cellular borders. Those places showed also an increased permeability of the labeled fibrinogen. We did not found similar affinities except with factor VIII and fibronectin. At present we can only speculate about the exact pathophysiological mechanisms of the relations between coagulation and capillary permeability found in these and other investigations. Show more

Keywords: Coagulation, permeability, fluorescent microscopy, fibrinogen, fibronectin, interstitial space, ultraviolet microscopy

DOI: 10.3233/CH-1982-25-614

Citation: Clinical Hemorheology and Microcirculation, vol. 2, no. 5-6, pp. 561-577, 1982

Authors: Crone, C.

Article Type: Other

DOI: 10.3233/CH-1982-25-615

Citation: Clinical Hemorheology and Microcirculation, vol. 2, no. 5-6, pp. 579-579, 1982

Authors: Astrup, Tage

Article Type: Research Article

Abstract: When tissues in the body are damaged the injured cells release thromboplastin, plasminogen activator and substances enhancing cell migration and proliferation. Thereby are initiated processes of wound healing and tissue repair. Haemostasis and the termination of an exsudative process are secured by an extrinsic coagulation process initiated by tissue thromboplastin, which is supported by the intrinsic coagulation system by an activation of humoral coagulation factors caused by damaged platelets, and resulting in the formation of plasma thromboplastin. The fibrin formed serves as a matrix for the formation of a granulation tissue induced by the growth promoting substances released from …the cells causing migration and proliferation of fibroblasts and angioblasts. During this process the fibrin deposit undergoes resolution caused by activation of the fibrinolytic system. Plasminogen is converted to the active enzyme, plasmin, by the released tissue plasminogen activator. This extrinsic activation is supplemented by an intrinsic pathway by which a humoral plasminogen activator is formed in the blood. Excessive deposits of fibrin remain if the local process of fibrinolysis is unable to cope with the amounts of fibrin formed. This may result from a continuous release of thromboplastin at a site of injury or from a low content of plasminogen activator. Differences in repair processes in various tissues results from the differences in content of tissue thromboplastin and plasminogen activator. Tissues low in plasminogen activator are particularly vulnerable to local fibrin deposition, thrombosis and the formation of excessive amounts of reparative connective tissue. This is seen in the liver and in the kidney cortex. Disseminated deposition of fibrin causes the syndromes of disseminated intravascular coagulation or microembolism, which in acute phases may lead to defibrination, extensive fibrinolysis and death from haemorrhage. Termination of the initiating coagulation process by heparin may then revert the situation and paradoxically terminate haemorrhage. Show more

Keywords: Coagulation, fibrinolysis, tissue thromboplastin, fibrin

DOI: 10.3233/CH-1982-25-616

Citation: Clinical Hemorheology and Microcirculation, vol. 2, no. 5-6, pp. 581-594, 1982

Authors: Urbaschek, Bernhard | Urbaschek, Renate

Article Type: Research Article

Abstract: All definitions of various forms of shock, also those induced by gram-negative bacteria respectively their endotoxins, include the alterations of the microcirculation as an essential component. In regard to the initial phase of endotoxemia we found in all species studied, that alterations of the microvascular bed are the first detectable changes besides the drop in leukocytes and platelets. The endothelial cells increase in volume and deviations. This deviation of endothelial cells induces, besides the increase in permeation of plasma into the tissue, a direct contact of the content of the vessels with the basement membrane. Using the Texture …Analysis System morphometric results of the endothelial cells confirm the vitalmicroscopic observations. Endothelial cells cultured from human umbilical veins react with contractions after application of histamine and with degranulation after exposure to endotoxin. Also degranulation of periadventitial mast cells occurs early in the initial phase after endotoxin. In the hamster cheek pouch and the mesentery of the guinea pig local application of complement activated by endotoxin provokes degranulation of mast cells. Isolated complement fractions C3a and C5a have the same effect. In the status of tolerance against lethal doses of endotoxins induced by a detoxified endotoxin the endotoxin-caused alterations of the microcirculation described fail to occur. This fact provides additional evidence of the significance of the microvasculatory disturbances in the starter mechanism of the endotoxic effects. Show more

Keywords: Endotoxins, shock, endothelial cell, mast cell, complement

DOI: 10.3233/CH-1982-25-617

Citation: Clinical Hemorheology and Microcirculation, vol. 2, no. 5-6, pp. 595-603, 1982

Authors: Hutten, H.

Article Type: Research Article

Abstract: The most frequently used methods are: a. Perfusion can be measured by means of radioactive, diffusible (and inert) indicators such as β -emitters (85-Kr), single photon emitters (133-Xe) and positron emitters (11-C in CO2 , 13-N, 15-O in CO2 ): clearance method. b. The mean transit time can be determined by means of radioactive, nondiffusible indicators such as 123 (μ )-J, 131 (β − , μ )-J, 99m(μ )-Tc or 113 m(μ )-Jn specially after labeling human serum albumin (HSA) microaggregates diameter 0,01–0,02 µm) with the indicators. c. The velocity of the blood stream at a particular point …in selected small vessels can be determined by (i) intravital microscopy (nailfold capillaries) or (ii) very high frequency ultrasonic Doppler method. d. Supply conditions can be investigated by means of (i) oxygen microelectrodes, specially in skeletal muscle, and (ii) administration of radioactive indicators, preferentially of the positron emitters 15-O and 11-C which can be linked to glucose. e. Metabolism (consumption) can be determined by application of the same positron emitters as in d. Perfusion can be measured by means of radioactive, diffusible (and inert) indicators such as β -emitters (85-Kr), single photon emitters (133-Xe) and positron emitters (11-C in CO2 , 13-N, 15-O in CO2 ): clearance method. The mean transit time can be determined by means of radioactive, nondiffusible indicators such as 123 (μ )-J, 131 (β − , μ )-J, 99m(μ )-Tc or 113 m(μ )-Jn specially after labeling human serum albumin (HSA) microaggregates diameter 0,01–0,02 µm) with the indicators. The velocity of the blood stream at a particular point in selected small vessels can be determined by (i) intravital microscopy (nailfold capillaries) or (ii) very high frequency ultrasonic Doppler method. Supply conditions can be investigated by means of (i) oxygen microelectrodes, specially in skeletal muscle, and (ii) administration of radioactive indicators, preferentially of the positron emitters 15-O and 11-C which can be linked to glucose. Metabolism (consumption) can be determined by application of the same positron emitters as in d. There is no ideal method which complies with all requirements. Thus, the limiting factors of each method have to be taken into account for each special application. Despite of evident advantages, radioactive indicators show also some restrictive disadvantages: (i) poor spatial resolution (dimension: ml) which only in special cases can be improved by application of mathematical procedures (e.g. peeling); (ii) for diffusible indicators: the dependence on the blood-tissue partition coefficient, particularly on the local hematocrit. (iii) for non-diffusible indicators: the recirculation problem and, dependent on the form of application, high radiation exposure; (iv) for positron emitters: the short physical half-time (several minutes) which necessitates the neighborhood of a cyclotron; (v) limited accuracy (and even reproducibility) due to: a) the form of administration (inhalation, intravenous or intraarterial injection, infusion) which affects the input function; b) the error of measurement statistics, temporal resolution errors, noise scatter etc.; c) discontinuous measurement: usually the measured parameter must be constant during the measurement period. poor spatial resolution (dimension: ml) which only in special cases can be improved by application of mathematical procedures (e.g. peeling); for diffusible indicators: the dependence on the blood-tissue partition coefficient, particularly on the local hematocrit. for non-diffusible indicators: the recirculation problem and, dependent on the form of application, high radiation exposure; for positron emitters: the short physical half-time (several minutes) which necessitates the neighborhood of a cyclotron; limited accuracy (and even reproducibility) due to: the form of administration (inhalation, intravenous or intraarterial injection, infusion) which affects the input function; the error of measurement statistics, temporal resolution errors, noise scatter etc.; discontinuous measurement: usually the measured parameter must be constant during the measurement period. If these restrictive aspects are carefully taken into account, the application of radioactive indicators permits detailed Show more

Keywords: Microelectrodes, radioactive indicator, positron emitter, clearance method

DOI: 10.3233/CH-1982-25-618

Citation: Clinical Hemorheology and Microcirculation, vol. 2, no. 5-6, pp. 605-615, 1982

Authors: Bollinger, A.

Article Type: Research Article

Abstract: Dynamic studies of human skin microcirculation by intravital videomicroscopy became possible using four different methods: Measurement of capillary red cell speed, continuous capillary pressure measurements, visualization of diffusion and pericapillary distribution of Na- fluorescein and fluorescence microlymphography. The latter two techniques are presented in some detail. In normals, Na- fluorescein which is given intravenously as a bolus (1ml of a 20 % -solution) leaves the capillary lumen showing a uniform and symmetrical pattern of pericapillary dye distribution (evaluation of fluorescent light intensities by videodensitometer, single frames of TV- recordings). Increased leakage and pathological dye distribution in the interstitial space is …observed in microangiopathy due to scleroderma. In white atrophy, a common feature in chronic venous insuffiency, Na- fluorescein diffuses into the avascular field (mean diameter 1 mm) and reaches its peak concentration at the centre only after 30–40 min (around normal capillaries in the ankle region: 10 min). The long times needed for the exchange of small molecules explains that white atrophy is a predilection site of venous ulcer formation. For fluorescence microlymphography a 25 % solution of fluorescent dextran with a molecular weight of 150’000 (0,01ml) is injected into the subepidermal layer by a steel microneedle with an outer diameter of 0,2 mm. The superficial lymphatic capillaries are filled from the deposit of the dye. In lymphedema, the fluorescent dextran visualizes an extensive network, whereas in normals the extension of the dye remains limited. In some patients pathological microvessels appear. Show more

Keywords: Nail fold, videomicroscopy, capillary pressure, fluorescence microscopy, permeability

DOI: 10.3233/CH-1982-25-619

Citation: Clinical Hemorheology and Microcirculation, vol. 2, no. 5-6, pp. 617-627, 1982

Authors: Lund, Frederik

Article Type: Research Article

Abstract: The technique and applicability of macro- and micro-fluorescein angiography (Ma-FA and Mi-FA respectively) after i.v. injection of sodium fluorescein are described, in particular permeability, besides evaluation of nutritional blood perfusion. Also, a recently developed method of “Intravital fluoescence capillary microscopy without a microscope” is reported which is achieved by ultraclose-up Ma-FA. This technical approach can give valuable information not only on blood perfusion but also on transcapillary fluorescein diffusion of separate capillaries as well as on fluorescence of the interstitium, both in the nailfolds, many other skin areas and in mucous membranes too. Certainly the technique does not reflect …details in the fluorescein diffusion pattern of the capillaries so accurately as does true Mi-FA. However, it is simple, versatile, non-expensive and universally applicable to different regions of the body. The field of image as well as the depth of field is greater than in true Mi-FA. For many purposes these advantages of ultra close-up Ma-FA may become decisive in the choice of technical approach. A preliminary report is given on a new clinico-chemical method of studying normal and abnormal microvascular permeability, as well as effective capillary surface area accessible to perfusion, by determining 6erum concentration levels in sequential blood samples after i.v. injection of the partially free, diffusible sodium fluorescein and for comparison also of the completely protein-bound, non-diffusible Evans Blue (T 1824). Main object of study is the extraction of sodium fluorescein from blood plasma to tissues, and in particular during the first circulatory phase after i.v. injection. The use of the procedure for assessing increased microvascular permeability e.g. in diabetic microangiopathy is illustrated. Show more

Keywords: Permeability, fluorescence angiography, diabetic microangiopathy

DOI: 10.3233/CH-1982-25-620

Citation: Clinical Hemorheology and Microcirculation, vol. 2, no. 5-6, pp. 629-652, 1982

Authors: Bartelheimer, H. | Schwartzkopff, W.

Article Type: Research Article

Abstract: One factor in the pathogenesis of atherosclerosis is an alteration in permeability to lipids and lipoproteins in the wall of the greater vessels, of the arterioles and of capillaries. A model to study the permeability of capillaries is the cantharidine blister fluid (CBF) and the filtrate which is passing through the membrane of the cantharidine-blister-base after applying negative pressure from 40 to 100 torr. The concentration of lipids etc. is lower in the blister fluid than in the serum. There is no relation between the sieving quotient C2/C1 of proteins (0,65) and of lipids in type IIa (0,49), in …type lIb (0,41), and in type IV (0,38). The concentration of lipids and lipoproteins in the CBF was not strictly correlated to those of the serum. In type IV the diffusion of the TG was more restricted (0,39) than in type IIb/a (0,40). The three fractions of lipoproteins (LDL, VLDL, HDL) had nearly the same relative distribution in the CBF as in the serum. The percentage of LDL and VLDL was in the CBF lower than in the serum. There is no difference of concentration for the HDL between both fluids. The sieving quotient C2/C1 for the lipoproteins etc. was different in the three HLP-types. TG, VLDL, CH and LDL were mostly restricted in type IV (C2/C1: TG = 0,39, VLDL = 0,38, CH = 0,36, LDL = 0,35). But the concentration of CH and LDL in the CBF was greater in type IIa/b than in type IV. The volume of capillary filtrate (ml/cm2 /min/mm Hg) was proportional to the negative pressure. With increasing filtrate volume the concentrations of lipids etc. decreased especially those of cholesterol and LDL. High blood pressure restricts the diffusion of cholesterol and LDL and promotes the deposition of these lipids in the vascular wall. Show more

Keywords: Permeability, cantharidine blister, hyperlipoproteinemia, cholesterol, filtration pressure

DOI: 10.3233/CH-1982-25-621

Citation: Clinical Hemorheology and Microcirculation, vol. 2, no. 5-6, pp. 653-668, 1982

Authors: Bollinger, A.

Article Type: Other

DOI: 10.3233/CH-1982-25-622

Citation: Clinical Hemorheology and Microcirculation, vol. 2, no. 5-6, pp. 669-669, 1982

Authors: Szabó, G.

Article Type: Research Article

Abstract: In normal dogs and rabbits plasma protein concentration is higher in tissue fluid than in lymph but after prolonged anaesthesis and immobilization tissue fluid protein concentration decreases, and the relationship is reverted. Chronic inferior v. cava constriction produces in dogs ascites and oedema. Protein content of tissue fluid and lymph decrease markedly, but tissue fluid concentration remains higher than lymphatic concentration. In acute thrombophlebitis with massive leg oedema protein content in tissue fluid and regional lymph do not change significantly. Both under normal and pathological conditions there is a linear correlation between tissue fluid and lymph protein concentrations. In …rabbits tissue injury was produced by burning the limb or by tourniquet application for 2 or 4 hr. After burning the increase in protein content was greater in tissue fluid than in lymph and there were big changes in lymphatic and tissue fluid activities of the cellular enzymes LDH and GOT. In normal animals LDH activity was about twice as high in tissue fluid as in lymph, but after burning its activity in tissue fluid became about 10 times higher than lymphatic activity. Total protein concentration in tissue fluid and lymph still showed in the burned leg a linear relationship, but the relationship between LDH activities was logarithmic. After ischaemic tissue injury in the body fluids there was again a big increase in the level of cellular enzymes especially in that of LDH and the increase was greater in tissue fluid than in lymph. Regional lymph flow was increased by intraarterial infusion of bradykinin but not by histamine. Lymphatic protein concentration increased by 45 % during bradykinin infusion, by 22 % during histamine infusion and by about 8 % in the controls. Tissue fluid protein concentration decreased in all experimental groups. A strong linear correlation was observed between tissue fluid and lymph concentration changes. The vasoactive agents increased the lymphatic transport of LDH. In the animals where lymph flow rate did not increase significantly the enzyme level in lymph rose markedly without a similar change in tissue fluid. At high lymph flow rates LDH in lymph was diluted, but the total enzyme flux was about 2 to 3 times higher than in the controls. In the tissue fluid no similar concentration changes were observed. It is concluded, that subcutaneous tissue fluid consists at least of two compartments, and only one of these, the perivascular interstitial space is drained directly by the lymph vessels. Consequently lymph represents essentially recent microvascular filtrate. The second compartment rinsing the cells and intracellular fibres is paralelly coupled with the first and is in exchange with it. In the normal state and under different pathological conditions there is a dynamic balance of macromolecular concentration in tissue fluid and lymph. The interstitial matrix seems to offer a substantial resistance to bulk flow and to macromolecular diffusion. This is reflected by the lack of equilibrium of extravascular plasma proteins between tissue fluid and lymph and by the considerable concentration gradient of cellular protein when their release is enhanced by injury. Show more

Keywords: Tissue fluid, lymph, macromolecular permeability, extravascular plasmaprotein, edema

DOI: 10.3233/CH-1982-25-623

Citation: Clinical Hemorheology and Microcirculation, vol. 2, no. 5-6, pp. 671-682, 1982

Authors: Földi, M.

Article Type: Research Article

Abstract: In a paper entitled “Lymphoedema: The case for doubt” (Brit.J. Plast. Surg. 21 (1968), 32–44) Calnan rejected the generally accepted pathophysiological basis of Lymphoedema. His arguments are:1. The age of onset in primary lymphoedema. Calnan finds it difficult to understand why a single hypoplastic lymphatic trunk which has served for the efficient return of lymph for 15 to 20 years begins to fail in its job without any obvious cause. Still more difficult to understand for Calnan is the case of the much older woman who has successfully passed adolescence, pregnancies and a very active life of sport before lymphoedema …appears. 2. Calnans next problem is female dominance in primary lymphoedema. According to him, the classical concept of lymphoedema does not account for this difference. 3. In 80 per cent of patients with primary lymphoedema the left leg is oedematous. The left common iliac vein is crossed by the right common iliac artery opposite the body of the 5th lumbar vertebra. According to Calnan the vein, which drains virtually all the blood from a leg, becomes compressed between artery and bone. Is “lymphoedema” in these cases an oedema of venous origin? 4. Sometimes lymphography shows normal lymphatics in patients with a clinically typical lymphoedema. How these cases can be explained? 5. Sometimes lymphography shows abnormal lymphatics in limbs free of oedema. How these cases can be explained? 6. At the time of radical mastectomy the surgeon may destruct the lymphatic pathways in the axilla completely and one would expect lymphoedema to follow. Yet in more than 80 per cent of patients there is minimal or no swelling. Why? The age of onset in primary lymphoedema. Calnan finds it difficult to understand why a single hypoplastic lymphatic trunk which has served for the efficient return of lymph for 15 to 20 years begins to fail in its job without any obvious cause. Still more difficult to understand for Calnan is the case of the much older woman who has successfully passed adolescence, pregnancies and a very active life of sport before lymphoedema appears. Calnans next problem is female dominance in primary lymphoedema. According to him, the classical concept of lymphoedema does not account for this difference. In 80 per cent of patients with primary lymphoedema the left leg is oedematous. The left common iliac vein is crossed by the right common iliac artery opposite the body of the 5th lumbar vertebra. According to Calnan the vein, which drains virtually all the blood from a leg, becomes compressed between artery and bone. Is “lymphoedema” in these cases an oedema of venous origin? Sometimes lymphography shows normal lymphatics in patients with a clinically typical lymphoedema. How these cases can be explained? Sometimes lymphography shows abnormal lymphatics in limbs free of oedema. How these cases can be explained? At the time of radical mastectomy the surgeon may destruct the lymphatic pathways in the axilla completely and one would expect lymphoedema to follow. Yet in more than 80 per cent of patients there is minimal or no swelling. Why? Calnans problems are analyzed and his questions are answered. The evidence shows that lymphoedema can be defined as the result of a low output failure of lymph flow in combination with a deficient extralymphatic mastering of stagnating plasma proteins. Show more

Keywords: Lymph edema, extravascular plasma proteins, lymph valve, lymph node

DOI: 10.3233/CH-1982-25-624

Citation: Clinical Hemorheology and Microcirculation, vol. 2, no. 5-6, pp. 683-690, 1982

Authors: Neuhof, H.

Article Type: Research Article

Abstract: If the oxygenation of blood is not critically diminished, the oxygen transport to the tissues and thus the total oxygen consumption of the organism is limited by the function of microcirculation. The organism’s total oxygen consumption therefore decreases if shock develops. The total oxygen consumption can be easily measured continuously as the total oxygen uptake of the patient. In this way the impairment of tissue perfusion all over the organism may be quantified indirectly by the reactions in the aerobic metabolism. In shock patients an inadequate tissue perfusion is always followed by a decrease in total oxygen uptake even …if hemodynamics may pretent good conditions for the microcirculation. Comparable to shock states, the microcirculation may also be affected during extra corporeal circulation. Although a complete blood oxygenation can be performed easily and pump flow can be set to an optimal range, tissue perfusion may be insufficient. Even in this situation changes in total oxygen consumption reveal the status of microcirculation and the reactions in capillary gas exchange. Show more

Keywords: Shock, oxygen consumption, extracorporeal circulation, norepinephrine

DOI: 10.3233/CH-1982-25-625

Citation: Clinical Hemorheology and Microcirculation, vol. 2, no. 5-6, pp. 691-703, 1982

Authors: Hauss, W.H.

Article Type: Research Article

Abstract: The microcirculation takes place in 2 histological areas, in an intravascular and in an intramural part. Both parts are produced by vessel wall cells which are mesenchymal cells. A larger number of heterogenous stimuli and injuries, especially the so-called risk factors, directly and regularly induce a reactive alteration of the mesenchymal metabolism (the “non-specific mesenchymal reaction”). Two types of the intramural part are serving for the microcirculation: a) the intramural part in the vessel wall and b) the intramural part in the capillary wall. The histological consequences of the reactive pathological metabolism in the intramural …part are described particularly with regard to the pathogenesis of arteriosclerosis of circulatory disturbances. Show more

Keywords: Arteriosclerosis, arterial wall, myocard, hypertension, diabetes

DOI: 10.3233/CH-1982-25-626

Citation: Clinical Hemorheology and Microcirculation, vol. 2, no. 5-6, pp. 705-719, 1982

Authors: Meßmer, K. | Sunder-Plassmann, L. | v. Hesler, H. | Endrich, B.

Article Type: Research Article

Abstract: Hemorheological disorders include both impairment of the flow properties and the flow conditions of blood. Hyperviscosity of blood and the low flow are the most important prominent factors to cause hemorheological abnormalities. Since impaired fluidity of blood and uneven distribution of blood flow was found in peripheral vascular occlusive disease, improvement of blood fluidity by hemodilution has been suggested as a form of conservative treatment. To further substantiate the few clinical studies available, the effects of hemodilution were analysed in an experimental model of peripheral arterial occlusive disease. The study comprised analysis of collateral blood flow, segmental vascular resistance, …distribution of resting and hyperemia flow as well as local oxygen supply to the skeletal muscle. Hemodilution by Dextran 60 was found a most effective method to decrease collateral vessel blood flow and to improve tissue oxygen supply by cancelling of the pathologic inhomogeneity of microflow. Show more

Keywords: Hemodilution, peripheral vascular occlusion, hyperviscosity, Dextran 60, collateral vessel

DOI: 10.3233/CH-1982-25-627

Citation: Clinical Hemorheology and Microcirculation, vol. 2, no. 5-6, pp. 721-731, 1982

Authors: Haanen, C. | Holdrinet, R.

Article Type: Research Article

Abstract: Disseminated thrombotic microangiopathy was until recently a fatal disease consisting of thrombocytopenic purpura, hemolytic anemia and progressive focal neurologic disturbances. Pathologically widespread hyaline occlusions are found in terminal arterioles and capillaries, which show enthothelial hyperplasia. The thrombi consist of platelets. This syndrome was first described by Moschcowitz in 1925 and is known in literature as thrombotic thrombocytopenic purpura (T.T.P.). In 1977 Byrnes and Khurana reported dramatic therapeutic responses in this hitherto fatal disorder, obtained by plasma infusions. Nine patients are described of which six were treated by massive plasma infusions, four which recovered completely. The experiences suggest the existence …of a plasma factor that is lacking or consumed in these patients and the producticn of which is modulated by the levels of estrogen/progestagen in the plasma. Identification of this anti-T.T.P. factor will be of great interest for understanding and treatment of T.T.P. and of increased platelet aggregation tendencies in general. Show more

Keywords: Disseminated thrombotic microangiopathie, Moschcowitz syndrome, thrombotic thrombocytopenic purpura

DOI: 10.3233/CH-1982-25-628

Citation: Clinical Hemorheology and Microcirculation, vol. 2, no. 5-6, pp. 733-743, 1982

Authors: Merlen, Jean F.

Article Type: Research Article

Abstract: Capillary disturbances are pathological confines of dermatology and angiology. The word “histangiopathy” must be prefered to the one “microangiopathy” (CURRI and MERLEN). According to the nomenclature established in 1972 by the International Union of Angiology, we distinguish 1) permanent acrosyndromes as Acrocyanosis, a group of six facets, where hypotonia and stasis in the capillary-venular anastomoses, more numerous than normally and above all more enlarged (MERLEN and CURRI 1965), beside chillblains, livedo, red palms and soles ... pure subjective acrorhigosis is at the base. 2) Paroxystic acrosyndromes due to coldness, Raynaud type or to heat, erythermalgia type. Raynaud’s phenomenon …and diseases are exposed, nobody has the right to assimilate Raynaud and sclerodermia or loco regional arteriopathy. There is a peculiar pattern of pulpar biopsy. Erythralgia, erythermalgia, acroerythrosis, acromelalgia, causalgia and Sudeck’s dystrophy are very near one another. 3) Dystrophic disturbances are intermediary forms with organic histangiopathies . The former concern livedo racemosa, perniosis, acrodynia, ulcero-mutilating acropathies. The latter are relative to dermatological lesions in the superficial or deep layers of the skin and they are quite different in clinical, anatomical and pathogenical aspects although a relative unity is however secured. A special attention must be paid to the diabetic microangiopathy due to stasis in the capillary-venular segment and shunting of blood by permanent opening of A.V. Anastomoses and blocking devices. There are specific lesions of the myoepithelioid cells of the A.V.A. and of the pericytes. Show more

Keywords: Capillary disturbances, histangiopathy, acrosyndromes, Raynaud’s syndrome, erythralgia, diabetes

DOI: 10.3233/CH-1982-25-629

Citation: Clinical Hemorheology and Microcirculation, vol. 2, no. 5-6, pp. 745-751, 1982

Authors: de Nicola, P. | Tassi, G.

Article Type: Research Article

Abstract: During aging there are significant modifications of the mechanism of hemostasis, including blood coagulation, fibrinolysis, platelets and vascular factors. A tendency toward thrombophilia is usually observed in the presenile age (45 to 60) with an increase of coagulability (reduction of antithrombin III and increase of fibrinogen turnover), a decrease of fibrinolytic activity and an increase of platelet aggregation. In the actual senile age, after 70, such a tendency may disappear and normal values or even signs of hypocoagulability may be found, in association with an increased capillary fragility and hemorrhagic diathesis. The thrombophilic tendency may be more marked in the …presence of predisposing diseases such as diabetes, hypertension, obesity and atherosclerosis. Today the role of gamma-carboxy-glutamic acid has been emphasized, insofar the abnormal proteins, which are formed due to the action of antivitamin K (indirect anticoagulants) or in the absence of vitamin K (as in malabsorption syndrome, frequently observed in the aged), do not contain gamma-carboxy-glutamic acid and act through an inhibition of factor Xa,thus increasing indirectly the antithrombin III activity. Therefore indirect and direct anticoagulants may be similar in this respect, namely enhancing antithrombin III activity. Thrombophilia in the arteriosclerotic aged subjects may be interpreted today as the consequence of a latent, intravascular coagulation syndrome. Besides the increased capillary fragility in the aged, which may be corrected by means of a number of drugs (e.g. aminaphtone, “vascular factor”, etc.), the small vessels in the aged nay exhibit some typical findings, e.g, in the conjunctiva, especially in cases of arteriosclerosis, hypertension, diabetes etc. The action of some drugs on microcirculation may be evaluated by studying the modifications of the conjunctival vessels, in addition to the other findings concerning blood viscosity and erythrocyte deformability. Show more

Keywords: Coagulation, thrombophilia, fibrinogen, prothrombin, bleeding time, microcirculation in the aged

DOI: 10.3233/CH-1982-25-630

Citation: Clinical Hemorheology and Microcirculation, vol. 2, no. 5-6, pp. 753-763, 1982

Article Type: Other

DOI: 10.3233/CH-1982-25-631

Citation: Clinical Hemorheology and Microcirculation, vol. 2, no. 5-6, pp. 765-767, 1982