Transplantation of isolated islets of Langerhans is frequently followed by early loss of islet function. Because whether this is caused by insufficient vascularization or graft rejection is unknown, angiogenesis and microvascularization of islet grafts were studied in vivo by means of intravital microscopy. After transplantation of syngeneic islets in hamster dorsal skin-fold chambers, 97% (n = 66) of the islets exhibited the first signs of angiogenesis at days 2-4, characterized by sinusoidal sacculations and capillary sprouts. After 10 days, angiogenesis was completed, consisting of a microvascular network similar to those of islets in situ: arterial supply, afferent and efferent capillary loops, and venular drainage. Functional density of microvessels was 700.1 +/- 127.0 cm-1, and erythrocyte velocity was 0.58 +/- 0.35 mm/s. Intracellular insulin was demonstrated immunohistochemically. Electron-microscopic studies revealed normal fine structure of the capillary wall. The model allows in vivo analysis of microvascular phenomena occurring in host-vs.-graft reaction after allogeneic and xenogeneic islet transplantation. Furthermore, it may be used to quantitatively assess immunosuppressive regimens.

ZusammenfassungZiel der Untersuchungen war es, nach temporä-rer Ischämie eines umschriebenen Myokardbezirks das nach längerer Reperfusion resultierende Verhältnis von toten zu revitalisierten Herzmuskelzellen und dessen Einfluß auf das Kontraktionsverhalten des betrachteten Bezirks zu studieren.Bei 32 jungen Schweinen wurde eine Woche nach einer temporären Koronarokklusion das Versorgungsgebiet der betroffenen Arterie mit Lichtgrün markiert; dann wurden in Gefrier schnitten des gesamten Herzquerschnitts GOT und SDH angefärbt. Die enzymfreien i.e. nekrotischen Flächen wurden denen des Versorgungsgebietes gegenübergestellt. Bei 20 von diesen Schweinen waren die Bewegungen intramyokardialer Metallmarker in der Randzone des ischämischen Bezirks röntgenkinematographisch beobachtet worden. Wir fanden, daß das Verhältnis von Nekrose zu Versorgungsgebiet in direkter Relation zur Ischä-miedauer steht. Bei 15 bis 30 Minuten Ischämie traten erste zentrale Nekrosen auf; bei längerer Okklusion dehnten sich diese zentrifugal aus und nahmen bei 45 Minuten 26%, bei 60 Minuten 34%, bei 90 Minuten 51%, bei 180 Minuten 61% und bei permanenter Okklusion 81% des Versorgungsgebietes ein. Wenn der nekrotische Anteil 30% betrug, war die Kontraktionsfähigkeit des gesamten Versorgungsgebietes auf 30-40% der Werte vor Ischämie reduziert, mehr als 50% Nekroseanteil führten zur Adynamie des gesamten Bezirks. Histochemical Studies of the Extension of Necrosis Following Temporary Regional Myocardial Ischemia in PigsThe purpose of the investigations described was to determine the relation between necrotic and resuscitated myocardium after a prolonged period of reperfusion following temporary regional ischemia. The influence of this relation on the behaviour of contraction of the primarily ischemic area was studied.In 32 young pigs a temporary coronary artery occlusion of 15-180 minutes was performed. One week later the area supplied by the afflicted artery was stained with lightgreen. Afterwards the hearts were removed and cold microtome sections of the entire diameter were taken for GOT-und SDH-staining.The areas free of these enzymes were compared with those marked with lightgreen. In 20 of the pigs the movements of intramyocardial metal markers within the ischemic area had been studied before, during and up to one week after the occlusion cineradiographically.It was found that the extent of the necrotic area A N within the supplied area A y depended on the duration of ischemia. After 15 to 30 minutes of occlusion necrosis appeared in the centre, after 45 minutes 26%, after 60 minutes 34%, after 90 minutes 51%, after 180 minutes 61% and after permanent occlusion 81% of the area supplied by this artery were found to be dead. When 30% of the supplied area were necrotic, the amount of active movements of the supplied area was reduced to 30-40% of the preocclusion value. When the necrotic area was larger than 50%, the whole area was akinetic.

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Summary and Conclusions The effect of particle ingestion on the activity of certain enzymes of mononuclear (MN) and polymorphonuclear (PMN) exudate cells and alveolar macrophages (AM) was evaluated by quantitative and semiquantitative histochemical techniques. The particles were yeast and chicken red blood cells in the presence of immune serum, and polystyrene in the presence of normal serum. The enzymes were acid and alkaline phosphatase, esterase and succinic dehydrogenase—enzymes probably more concerned with metabolic than with digestive phenomena. The period of ingestion usually varied from 10 to 40 min, in tubes attached to a drum rotating at 6 rpm. Phagocytes containing particles were found to have the same amount of histochemically detectable enzymes as adjacent phagocytes on Mylar strips that had not ingested particles. In other words, the ingestion of particles was not associated with an increased content of enzymes. Biochemical studies on the acid phosphatase of frozen and thawed MN and PMN that had ingested various particles confirmed this conclusion. However, manometric studies under similar conditions showed that the phagocytic process increased the respiration of viable cells. This suggests that their metabolic enzymes, although unchanged in amount, were utilized more fully. The effect of particles on the enzymes of phagocytes was also evaluated over longer periods of mutual association. For this purpose rabbit mononuclear exudate cells were allowed to ingest yeast particles and then were cultured along with controls in 98% autologous serum, a method adopted from Dr. Y. T. Change of the National Institutes of Health. Zero- and 48-hr Mylar strip preparations then were made from these cell cultures for quantitative histochemical evaluation. Not all experiments were successful, but in those that were, the 48-hr cell preparations containing yeast showed a significant increase in the number of MN with high esterase and acid phosphatase contents. This seemed to be associated with digestion of the yeast particles. Although other interpretations are possible, we feel that the increased enzyme content of these cells was due to an adaptive response to the intracellular presence of particles. The above findings are consistent with the following concept: a) An initial protoplasmic excitation, brought about by collision with particles and/or their actual ingestion, results in an increase in the oxygen consumption of intact cells. Such phagocytes are activated, in that they ingest the particles more readily and probably have increased motion and pseudopod formation. Their enzymes are not increased in amount, but seem to be utilized nearer their full capacity and may have a different distribution within the cell. b) This excitatory response initiates and merges with protoplasmic adaptation which is a more lasting response on the part of the phagocyte to ingested material and other irritants. It is expressed by an increase in certain enzymes, and specific and nonspecific changes in the phagocytic, bactericidal and digestive powers of the cell. These two phases of phagocytic activation may be crucial to the host's defense against infectious disease.