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

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