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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 microcirculation. 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.

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.

The objective of this article is to briefly review our present knowledge of the pattern, the functional behaviour and the fine structure of the cutaneous papillary vessels and their alterations under various pathological conditions. The shape of these capillary loops varies within wide ranges dependant on the functional state of the covering epidermis. If the latter is hyperplastic the vessels are elongated, twisted and coiled. In case of epidermal atrophy the capillaries become shorter, decrease in number until their final complete absorption. At the level of the electron microscope the capillary wall clearly shows to consist of 2--3 or more endothelial cells of high electron density encircling an always narrow lumen. Both the inner and outer endothelial surfaces are irregular in outline and the cytoplasm is crowded with filaments of 50--70 A in diameter. In addition it is characterized by the occurrence of a larger number of vacuoles and Weibel-Palade bodies, the latter serving as an excellent marker for endothelial cells to e.g. clearly decide the morphogenesis of certain vascular tumors. Along their apex the capillary loops show a fenestrated endothelium particularly at their adepidermal sites. The basal lamina is multilayered and thereby giving a scroll-like appearance in cross sections. At the ultrastructural level endothelial cells are only provided with a limited repertoire of reactions to noxious stimuli. Among these are: (1) an increase in vesiculation and organelles, (2) the formation of cytoplasmic processes often accompanied by the development of interendothelial "gaps" and (3) alterations - mostly thickenings - of the basement membrane. These different fine structural changes were shown to also occur in various diseases of the skin including it's vascular tumors. In experimental research of the skin microvasculature the most spectacular technique was that of a human skin chamber as originated by Branemark. Thereby most of our older findings as to the functional behavior of the microcirculation in laboratory animals were shown to be valid and hence transferable to humans provided similar experimental approaches were used. Finally the vitalmicroscopy and ultrastructure of tumors (melanoma, hemangiopericytoma and neurilemmoma) transplanted into the hamster cheek pouch are briefly outlined.

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.

Two different types of paracrystalline mitochondrial inclusions identical with or very similar to those already described in the literature for a variety of muscle diseases were found in human skeletal muscle biopsies obtained under general anesthesia before ischemia and after various periods of anoxia up to 150 min. As these crystalloids could be observed in seven of 14 healthy subjects and occurred in five of these seven cases either before or only 10 min after onset of ischemia, it is suggested that such mitochondrial inclusions develop not only under the influence of variant noxious stimuli, but may also represent a normal constituent of human skeletal muscle mitochondria.

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 micron phi, 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 X 10(-5) M. Concentrations of 3 X 10(-4) to 3 X 10(-3) M always sufficed to induce barrier opening for fluorescein, whereas 3 X 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.