Isolation, identification, and continuous culture of coronary endothelial cells from guinea pig hearts.

Viable and homogeneous endothelial cells were obtained from isolated guinea pig hearts by application of a special perfusion technique of the coronary system with an isotonic collagenase-trypsin solution and subsequent purification of the dissociated cells by Percoll density gradient centrifugation. The coronary endothelial cells were grown in tissue culture for periods up to 7 months. Serial passage proved to be possible. During logarithmic growth, generation time was found to be 18 h; it could be reduced to 16 h by addition of thrombin to the culture medium. Light, phase contrast and scanning electron microscopy as well as autoradiography revealed that cultured coronary endothelial cells grew as strict monolayers of closely apposed, polygonal large cells. By scanning electron microscopy, it could be demonstrated that the morphology of the cultured cells changes characteristically during attachment of the cells to their substratum. The changes observed were very similar to those of proliferating endothelial cells of isolated coronary vessels kept in organ culture. According to transmission electron microscopy studies, cultured coronary endothelial cells proved to contain only an extremely small number of Weibel-Palade bodies. Nucleoside phosphorylase (EC 2.4.2.5.) and 5'-nucleotidase (EC 3.1.3.5.) were identified in freshly isolated as well as in cultured endothelial cells. Their specific and total activities proved to be much higher than in myocardial tissue, thus indicating a prominent role of nucleotide metabolism in the coronary endothelium.

Collagen dysplasia and matrix vesicles. Researches with the electron microscope into the problem of so-called "weakness of the vessel wall".

Quite diverse pathological changes of the wall of a blood-vessel can lead to quantitatively and qualitatively altered collagen, as well as to the production of matrix vesicles. It can be demonstrated morphologically that changes--particularly qualitative changes--in collagen are accompanied by a more or less severe loss of function. Possible causal connections between the appearance simultaneously of matrix vesicles (in which lysosomal enzymes can be demonstrated) and altered vascular collagen are discussed.

An investigation into the fine structure of the ligated rat ureter.

The normal structure of the ureter of the rat is described and compared with the results of earlier work. Research on arteries left in situ stimulated morphological investigation of the ligated ureter proximally and distally to the ligature. As in ligated blood vessels, an increase in modified muscle cells with accompanying increase in connective tissue (particularly proximally to the ligature) occurs in the ureter. In association with quantitative changes, qualitative changes in the formation of collagen and in the arrangement of fibrils were found, although not so marked as in arteries subjected to "load failure". During a comparison of the ureteric walls on either side of a ligature intracellular collagen was found. The results of earlier work on ligated ureters are discussed, together with the present findings. The reactions of ureteric and arterial walls subjected to similar "load failures" are compared. Qualitative changes in the intercellular substance are considered in connection with the findings in cases of pathological processes in the walls of blood vessels. Several possibilities are suggested with regard to the interpretation of the intracellular collagen.

Dysplastic collagen fibrils in the human vocal fold. An electron microscope study.

Electron microscope studies made on biopsy samples of the human vocal cord from patients suffering from chronic hoarseness revealed pathological changes in both the collagen fibrils and the elastic fibres. There was splitting and fracturing of the collagen fibrils and lacuna or cyst formation in the elastic fibres, or even the complete fibre degeneration. Further investigations must be undertaken in order to establish whether the changes observed are of a primary or secondary nature.

[Chronic venous insufficiency]. / Die chronisch-venöse Insuffizienz.

In severe chronic venous insufficiency (CVI) the fascia cruris is increasingly involved in the pathological process. The resulting loss of compliance as a consequence of altered fascia texture leads to increased pressure in the compartments of the lower extremity, followed by reduced circulation. Arteries and nerves, which penetrate the fascia along with insufficient perforating veins, are damaged through the increased pressure and are therefore functionally impaired. Accordingly many pathological changes in the crural ulcer have their anatomical substrate here. The microcirculation is distributed by either primary varicosis with secondary insufficiency of the deep veins or by primary insufficiency of the deep venous system as seen in a post-thrombotic syndrome. Subsequent therapy should be based on this knowledge and therefore consists of medication and basic physical therapy along with dissection of the perforating veins-fasciotomy and fasciectomy combined with plastic surgery. All of the therapeutic measures have to take the stage of the CVI into consideration. In order to eliminate the insufficient perforating veins and to perform fasciotomy the endoscopic approach is considered the state of the art. In extreme cases, only fasciectomy combined with plastic surgery can lead to durable healing.

Intracavernous application of SIN-I in rabbit and man: functional and toxicological results.

The mode of action of the active metabolite SIN-I of the vasodilator prodrug molsidomine was studied in vitro and in vivo in corpus cavernosum of rabbit and man. SIN-I produces a dose-dependent relaxation of isolated human cavernous smooth muscle strips. In the rabbit, the intracavernous application of SIN-I increased the intracavernous pressure to a full erection (approximately 100 cm H2O). This response was highly reproductible. SIN-I was also injected intracavernously 6 times in five rabbits over 2 weeks; no inflammatory or fibrotic reactions were found on histology. SIN-I may be a reliable drug for the treatment of impotence without side-effects.

[New concept of the pathogenesis of varicose disease]. / Conception nouvelle de la pathogénie de la maladie variqueuse.

The author explains his research into the ultrastructure of the pathological venous wall. From his findings he describes his conception of the pathogeny of primary varices and emphasizes the degeneration of the enzymatic origins of the collagenous tissue, inter and intrafibrillar. The muscular cell is affected and the transmission of nervous influx is carried out imperfectly.

[A new concept of the pathogenesis of medial dysplasia (author's transl)]. / Ein neuer Aspekt zur Pathogenese der Mediadysplasie: Myozytentransformation, Matrix Vesikel und extrazelluläre Lysosomen in der Wand fehlbelasteter Blutgefässe.

A unifying concept may be set out briefly in the following manner: injurious agents (such as abnormal hemodynamic and/or metabolic conditions--"risk factors for the vessel wall") leads to the transformation of contractile (k) smooth muscle cells into the metabolically more active or "modified" (m) variety leads to an increase in the number of intracellular and extracellular lysosomes (matrix lysosomes) leads to medial dysplasia. The vague concept of a "vessel wall weakness" as the cause of aneurysms, varicose veins etc. has given place to a more precise picture, following the E. M. demonstration of atypical (i.e. dysplastic) collagen fibrils and elastic fibres. The muscle cells of the vessel wall appear to react to the altered conditions with an icrease of lysosomes, and therefore of lysosomal enzymes. The E. M. has also revealed collagenolysis, elastolysis and proteoglycanolysis in the vicinity of matrix lysosomes.

The ultrastructural characteristics of abnormal collagen fibrils in various organs.

Quite unrelated diseases affecting different organs can lead to the appearance of abnormal collagen fibrils, which may be due to genetic disorders, transformation of mesenchyme cells, increased collagen synthesis or a change in the ground-substance. The simultaneous appearance of abnormal collagen fibrils and matrix vesicles containing lysosomal enzymes in the majority of our electron photomicrographs suggests an alteration in the ground-substance as a main cause of non-hereditary collagen dysplasia.

[Anatomical study on the constancy of Cockett's perforating veins]. / Etudes anatomiques sur la constance des perforantes de Cockett.

The tenet of the constancy of Cockett's perforating vessels does not hold against anatomical studies. They perforate the fascia at various levels as their relationship to Linton's line also vary. Finally, they originate, most of the time, from the communicating veins connecting the posterior leg branch and the internal saphenous vein.