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Release of arachidonic acid (AA) in brain tissue is found in various cerebral insults. Blood-brain barrier function and vasomotor response were studied during cerebral administration of the fatty acid to obtain further evidence on its role as mediator of secondary brain damage under pathological conditions. Na+-fluorescein or fluorescein isothiocyanate (FITC)-dextran were i.v. administered as low- and high-molecular weight blood-brain barrier indicators. Cortical superfusion of arachidonic acid led to moderate constriction of ca. 90% of normal of pial arteries of 60–220 µm Ø, whereas the venous diameters remained unaffected. On the other hand, AA caused opening of the blood-brain barrier not only for Na+-fluorescein but also for FITC-dextran (mol.wt. 62,000). Extravasation of Na+-fluorescein started at AA concentrations of 3×10-5 M. Concentrations of 3×10-4 to 3×10-3 M always sufficed to induce barrier opening for fluorescein, whereas 3×10-3 M was required for FITC-dextran. Leakage of the blood-brain barrier indicators started around venules. Pretreatment with indomethacin, or with BW 755 C, a dual inhibitor of both the cyclo- and lipoxygenase pathway did not prevent barrier opening by arachidonate for Na+-fluorescein. However, in the presence of indomethacin higher concentrations of AA were required to open the barrier for Na+-fluorescein, whereas BW 755 C did not influence the dose-effect relationship of AA and barrier opening observed in untreated animals. The latter findings imply that the pathophysiological effects induced by AA are likely to be attributed to the acid itself, rather than to its metabolites, a conclusion which might be in conflict with earlier observations reported in the literature. Electron microscopy revealed marked alterations of the venous endothelium, such as an attachment and eventual penetration of polymorphonuclear granulocytes through the endothelial barrier, while the small arteries and arterioles were unaffected. The findings may indicate that opening of the barrier by AA is mediated by granulocytes and/or their products. Taken together, our findings support the concept that release of AA in primarily damaged brain tissue enhances secondary processes, such as a failure of the blood-brain barrier function. The limited potency or even ineffectiveness, respectively, of indomethacin or BW 755 C provides evidence for a direct involvement of the fatty acid rather than of its metabolic degradation products. Therefore, therapeutic prevention of AA formation under these circumstances might be superior to mere inhibition of its metabolism.

Summary Clinical and electron microscopic studies of two female patients are reported who, in addition to the symptoms and signs of idiopathic edema, had pericardial (and pleural) effusions. In one patient pericardiectomy had to be performed, in the other patient pharmacotherapy with spironolactone was effective. In these patients the protein-concentrations of edema fluid (25 and 12 g/l) and pericardial fluid (55–61 and 48 g/l) were relatively high; the distribution space of labelled protein was increased; blood volumes were low-normal or decreased. Electronmicroscopy of the microvasculature showed identical alterations in both cases. In the cutaneous vessels the endothelium developed numerous abnormal cytoplasmic processes and intercellular “gaps”. In the capillaries of skeletal muscle our findings indicate an increase in vesicular transport. We suggest the electron microscopic alterations to be the morphologic correlate for the increased transport and extravascular accumulation of protein. Changes as they are described here in humans with idiopathic edema have been documented before in animals with experimental edema.

Summary Contrary to our former belief, endothelial cells can no longer be classified as a homogeneous cell population which, as a living border layer between the blood and the extravascular space, serves exclusively as a selective filter. The technique of routinely culturing endothelial cells from various sources has provided new insights into an unexpected multitude of synthetic and metabolic capacities of these cells, such as the degradation of arachidonic acid, the enzymatic activation of angiotensin I, and many others. However, many of these results are still contradictory, and therefore make any critical review of the data almost impossible. Some examples for this are briefly outlined in this contribution. Irrespective of this, these new results have to be taken into account, although the possibly high specificity of the endothelium will render the interpretation of future data, particularly those obtained from animal models, much more difficult. However, a simple neglect of these complexities would be disastrous for all future endothelial research.

Summary: The effects of repeated local exposure to cold on the integrity of the subcutaneous microcirculation were studied in a model using a transparent tissue chamber implanted into a dorsal skin fold of Syrian hamsters. A detailed study of the vascular ultrastructure within the chamber revealed the following features: Endothelial damage was prominent in true capillaries and venous vessels, while arterioles remained unaffected. The endothelial lining appeared extremely attenuated around the entire vascular perimeter causing the development of “gaps”, some of which contained leukocytes or platelets. Smaller vessels were often completely filled with blood cells with leukocytes integrated into the endothelial wall. Fibrin was never observed within these occluded vessels. Finally, only veil-like remnants of the endothelium persisted, and compressed erythrocytes were still mimicking the original vascular outline. It is concluded that the ultrastructural changes observed after a repeated non-freezing cold injury closely resemble those observed during ischemia/reperfusion injury.

Summary Hypoxic regions of malignant tumors are poorly vascularized; they appear to be more susceptible to hyperthermia in vivo than tumor cells in vitro after an exposure to heat. In an attempt to explain this discrepancy, changes of microcirculatory flow in the tumor have been proposed as key mechanism for destroying adjacent tumor cells in particular. This study was conducted to define the impact of the microcirculation on tumor destruction after local hyperthermia. A transparent chamber was implanted in the dorsal skin fold and two permanent indwelling catheters placed in carotid artery and jugular vein of 45 Syrian golden hamsters. 48 h later, 4 × 104 cells of the amelanotic melanoma A-Mel-3 were implanted into the s.c. tissue covered by the chamber. 5 days later, at a tumor diameter of 3 mm, the microcirculation of this tumor was studied using intravital microscopy, a platinum multiwire electrode, television as well as micropuncture techniques for the determination of local PO2 microcirculatory blood flow and microvascular pressure. Measurements were taken at 30° C and 15 min after reaching a tumor temperature of 35° and 42.5°C. When heating up the melanoma to 35 °C, an increase in capillary perfusion by 35% was noted. With an apparent maximum of capillary perfusion, there was no change in arteriolar pressure but a significant drop in venular pressure from 11.0± 1.1 to 7.4±0.6 mmHg resulting in an increase of the arteriolo-venular pressure gradient while the systemic pressures were unchanged. At a tumor temperature of 42.5°C, prestasis and stasis became apparent in capillaries and collecting venules. This was accompanied by a rise in capillary and venular pressure by 5 mmHg. At the same time, pronounced tissue hypoxia was present in the tumor with more than 50% of the values within the hypoxic range between 0 and 5 mmHg. Despite tissue hypoxia, the constriction of all tumor arterioles became evident 15–30 min after reaching a tumor temperature of 42.5°C. The deterioration of tumor oxygenation was associated with damage of tumor cells such as swelling and destruction of mitochondria which was seen under the electron microscope. After 40 min at 42.5°C, the attenuation of the endothelial lining around the entire vascular perimeter was seen in tumor capillaries.Conclusion: The tumor microcirculation seems to be more sensitive to heat than the normal microcirculation. This implies that 1. the heat induced breakdown of the tumor microcirculation could explain the accelerated tumor destruction in vivo because tumor cells were already damaged 10 min after heat application with the destruction of tumor cells significantly preceding the changes at the capillary wall, 2. moderate heating (<40°C) should be preferred if hyperthermia is combined simultaneously with other treatment modalities, 3. the tumor is virtually excluded from the systemic circulation at a tumor temperature of 42.5°C since a pronounced arteriolar constriction was seen to persist for 72 h. Thus, cytotoxic drugs will not reach the tumor via the vasculature during this period.

The semitendinosus muscle of the rabbit is composed of a homogeneous fiber population. Fiber typing was carried out by means of light and electron microscopy according to which this muscle exhibits structural features that are either characteristic for both ‘red’ and ‘white’ fibers, or that do not allow for any classification according to the A-, B-, C-fiber system. Hence the long-held assumption that the semitendinosus muscle of the rabbit represents a classical paradigm of a ‘red’ muscle should be revised in light of the present results.

Summary: Intact blood supply by microcirculation to a wounded site is an indispensable prerequisite for normal tissue regeneration. However, microvascular changes taking place in the healing process of skin wounds are not understood due to the fact that only few models allow chronic in vivo studies on skin micro-circulation. Therefore, we have modified the hairless mouse ear model with the purpose of a quantitative in vivo study of microhemodynamic changes throughout the healing process. Following the creation of a standardized skin wound on the ear of the homozygous hairless mouse (hr/hr), microvessel diameters, red blood cell velocities, wet weight, and leucocyte content of the ear tissue were determined. Surface area of the wound was assessed until complete closure was achieved. By repeated measurements at identical sites over the entire healing period, a distinct pattern of microvascular changes could be observed: microvessel diameters increased to a maximum a few days after wound creation, whereas red blood cell velocities reached their highest values at a later point in time and were still elevated after complete reepithelization of the wounds. Edema and leucocyte content of the ear tissue was most prominent in the early healing phase and gradually decreased to normal values thereafter. These results demonstrate changes of the microvasculature of the hairless mouse ear to injury, which are in accordance to other more indirect studies on this topic. Therefore, we conclude that the model presented is suitable for prolonged quantitative analysis of microcirculation during normal wound healing and may be used to assess microvascular changes taking place during wound healing in pathologically altered tissue.

Die kleinen und kleinsten Arterien des Stratum periostale der menschlichen Pachymeninx sind durch wechselnd starke Schlängelungen gekennzeichnet. Sie zeigen stellenweise einen mäanderähnlichen Verlauf und „Knäuel“-Bildungen. Entsprechende Arterien finden sich auch in der Dura von Huhn und Kaninchen.

1.The capillaries in the m. tibialis ant. of the rat are characterized in certain areas by an unusually thin endothelium which is interrupted by pores and fenestrations. While the former represent true holes or openings in the endothelial layer, the latter are closed by a thin membrane, approx. 50–60 Å thick, the “diaphragm” of Rhodin. The diameter of both structures is similar and averages 500 Å.2.Seven minutes after injection of a solution of colloidal gold into the a. femoralis this substance is found just beneath the diaphragms of the fenestrations and in greater amounts within the true pores. In the thicker parts of the endothelial cells the electron-dense tracermaterial is always included in membranebounded vesicles, which sometimes have already reached the basal plasmalemma.3.The present and similar findings of other authors have led to a thesis to explain the formation of endothelial pores and fenestrations: In many cases these structures seemed to represent merely a transient arrangement, which could be formed by contact or fusion of micro-pinocytotic vesicles in extremely flattened endothelial cells.4.As to the functional significance of these endothelial structures our experiments point out, that (at least) for colloidal substances the fenestrations are not, like the real pores, main routes of transcapillary exchange.

1.Als Plexus perivascularis werden Strombahnen in den Bindegewebsräumen entlang der großen Gefäßstämme beschrieben, die innerhalb der Nierenschale verlaufen.2.Der Plexus perivascularis setzt das Gefäßsystem des Nierenbeckens in das Nierenparenchym hinein fort und wird zusätzlich durch unmittelbare Äste der Aa. rencularis und subcorticalis (sive arciformis) gespeist.3.Im Gegensatz zu allen Parenchymästen der Nierenschlagader bilden seine Arterien ein Netz. Sie gleichen in dieser Hinsicht dem Arterienmuster der Nierenbeckenwand und der Nierenkapsel.4.Anordnung und Verlauf der Arterien des Plexus perivascularis an den Gefäßstämmen der Interlobärräume und der Mark-Rindengrenze ähneln im Korrosionspräparat mitunter einem entblätterten, an alten Bäumen haftenden Efeugerank.5.Schnitte durch gewundene Arterienstrecken des Plexus können Glomusorgane (= arterio-venöse Anastomosen) vortäuschen. Auch die Anwesenheit arterio-arterieller Anastomosen kann Anlaß zu Verwechslungen mit arteriovenösen Kurzschlüssen geben, die hier bislang von uns nicht nachgewiesen werden konnten.6.Der Plexus perivascularis speist den Inhalt der intraparenchymatösen Bindegewebsräume (speziell über Vasa vasorum die Wände der großen Gefäße) und gibt Äste (= Arteriolae rectae verae) an die Markpyramide ab.7.Die Bedeutung des beschriebenen Gefäßsystems wird unter Berücksichtigung der Spiralarterien des Nierenbeckens diskutiert.8.In 5 Tabellen werden differente Befunde und Auffassungen zur Versorgung des Nierenmarks über Arteriolae rectae spuriae et verae zusammensgestellt.

1.Bei der Diagnose von arterio-venösen Anastomosen im Injektionspräparat sollten Extravasate, künstlich überdehnte Capillaren und Gefäßüberlagerungen sorgfältig in Erwägung gezogen und abgegrenzt werden. Die Schwierigkeiten bei der Analyse von Gefäßüberschneidungen im injizierten und aufgehellten Totalpräparat werden erörtert.2.Die Anwesenheit von arterio-venösen Anastomosen in der Wand menschlicher Nierenbecken wird diskutiert und in Frage gestellt.

The investigation deals with the fine structure of the segmentally organized, paired and contractile lateral vessel of Hirudo medicinalis L., whose layered wall shows the following structural characteristics.

In the adventitial cells of the arterio-venous anastomoses in the human glomus coccygeum peculiar inclusion bodies have been found which consist of hollow cylinders (diameter approx.: 800 Å, mean length: 2,000 Å), whose wall is composed of a concentrically layered membranous material. As the arrangement and the fine structure of the latter show close resemblance to a certain component of human mast cell granules, the evidence obtained so far led to the suggestion, that the cells described here either represent a specific (vascular ?) type or some final stage of human mast cells.

1. Die Angioarchitektonik im Periost langer Röhrenknochen von Hunden und Katzen wird beschrieben.

1.Der Pharynx der Hirudineen verfügt, ähnlich dem Ductcus deferns der Säuger, über einen Fördermechanismus zur Ansaugung und Austreibung einer Flüssigkeit.2.Die Schlundmuskulatur der Egel ist nicht in Gestalt kontinuierlicher, schraubig verlaufender Züge, sondern in getrennten Längs-, Ring- und Radiärbündeln angeordnet. Die Ausprägung dieser Muskelsysteme weist bei den untersuchten Arten einer Untergruppe der Hirudineen, den Gnathobdellae, erhebliche Unterschiede auf. Diese Differenzen werden auf die unterschiedliche funktionelle Beanspruchung des Schlundrohres durch die verschiedene Art der Nahrung und deren Aufnahme bezogen.3.Der Radiärmuskulatur, die den Pharynx in der Cutis verankert, kommt vor allem die Aufgabe eines „Dilatators“ zu. Sie ist demzufolge bei den typischen Saugegeln intensiv entwickelt. Darüber hinaus bildet sie mit den Längs- und Ringmuskelschichten ein dreidimensionales Muskelgefüge, das Verschiebungen unter der Funktion ermöglicht, da ein entsprechendes Bindegewebsgerüst fast völlig fehlt.4.Der Ductus deferens der Säuger und der Pharynx der Hirudineen besitzen trotz vergleichbarer funktioneller Beanspruchungen (Ansaugen und Fortbewegen einer Flüssigkeit) eine dem Prinzip nach unterschiedliche Wandkonstruktion.

Summary During an outbreak of a mild upper respiratory tract infection in a university children's hospital in Munich, an H1N1 influenza virus was isolated. Serological analysis of the isolate showed that antigenically the virus resembled the USSR/90/77 strain of influenza A virus which has been isolated in many parts of the world during the last two years.