N. Freudenberg

Experimental Investigations into the Pathogenesis of Endocarditis due to Shock

Generalized Shwartzman reaction (GSR) was induced in rabbits by two intravenous injections of endotoxin 24 hours apart. Consumption coagulopathy was found in all cases. Histological investigations showed an abacterial endocarditis (thrombotica or verruccosa simplex), comparable to the one seen in humans after shock, in 69% of the treated animals. Biopsies of mitral valve were investigated by electron microscopy. In the early stage of GSR the valvular alterations were characterized by an oedema of the entire valve, an increase in the number of microvesicles in the endothelial cytoplasm, and a marked enlargement of endothelial cell surface by numerous cytoplasmic projections. At a later stage autophagic vacuoles, often showing a destruction of their membranes, and degenerative changes in cytoplasmic organelles occurred in many cells of the valve. On the other hand there were cells in the endothelium, which presented a distinctly increased number of Golgi complexes and of cisternae of rough endoplasmic reticulum. In other regions ruptures of endothelial plasmalemma, as well as hemorrhages into the valvular stroma were observed. Thus predestined loci for thrombogenesis were formed. In conjunction with these structural changes three factors may be involved in the formation of endocarditis due to shock: 1. hypercoagulability in the course of consumption coagulopathy, leading to precipitation of fibrin and platelets in the circulating blood; 2. turbulences of the blood flow, which are produced by the closure of the heart valves, and favour thrombogenesis on valves: 3. direct changes of the endocardium during endotoxemia. Quantitative changes in the different compartments of intracytoplasmic organelles in many cells of the endothelium during the later stage of GSR are discussed.

Effect of endotoxin-induced shock on the reticuloendothelial system. Phagocytic activity and DNA-synthesis of reticuloendothelial cells following endotoxin treatment.

There was a marked decrease in the RES phagocytic activity during the first 12 hours after injection of high concentrations of endotoxin in rats. Phagocytic activity then increased considerably, reaching maximum values on days 3 to 5 and it was still higher than in control animals 20 days later. Parallel studies on 3H thymidine incorporation showed a significant increase in the rate of DNA-synthesis of reticulum cells of the liver during the 5 days period following endotoxin injection. Peak values were obtained on day 2 when the number of labelled cell were 50 times higher than in the controls. A likely reason for the increased DNA-synthesis is a repair of RES following endotoxin induced damage but it may also represent an endotoxin induced proliferation of reticulum cells that may at least partly account for the enhanced phagocytic activity.

Ultrastructure of Human Atrial Endocardium in Oxygen Deficiency Diseases

Summary The ultrastructure of the human endocardium in two patients suffering from oxygen deficiency diseases is described. In the endothelium the following alterations are observed: enlarged surface, increase of microvesiculation and of intracytoplasmic vacuoles, numerous fenestrations, pores and gaps, swelling of mitochondria, RER and SER, and increase in number of Golgi apparatus. The subendothelial space in the first case shows undifferentiated cells of mesenchymal origin, scarce collagen fibers and an edematous interstitium, in the second case the well-known layers with increased elastic fibers were found. No vessels were seen. The presence of smooth muscle cells can only be suspected by the finding of some axons. Finally, we have tried to correlate these observations, the clinical data and previous morphological findings in damaged endocardium. Possible differences between acute, chronic and transitory alterations are discussed.

Ultrastructural Investigation of Human Atrial Myocardium in Cardiac Malformation with Spezial Regard to Z-Band Alterations: Elektronenmikroskopische Untersuchung des menschlichen Vorhofmyokards bei einer Herzmißbildung mit besonderer Berücksichtigung von Z-Streifen-Veränderungen

Summary The ultrastructure of human atrial myocardium in Pentalogy of Fallot after atrial fibrillation and subsequent defibrillation during the operation is investigated. Various alterations like general oedema, changes of mitochondria, and of sarcoplasmatic reticulum as well as the reduction in the number of glycogen granules, and dehiscences of intercalated discs are discussed with regard to their pathogenesis. Of special interest are numerous alterations of 2-bands. First there are various kinds of contraction bands, which are mainly due to acute damage of atrial fibrillation and defibrillation. These supercontractions and the other changes in the myocardial cells do not lead to alterations of the postoperative electrocardiogram. Secondly Z-band material near cell membranes is apparent, reminding of pictures of neofibrillogenesis. Finally, defined changes of Z-bands are found which resemble those in heart hypertrophy, or in some muscular diseases, and in the aging process of muscle cells. The authors conclude that Z-band material is a very reactive part of the myofibril, by changing its normal structure when exposed to different influences, perhaps not only pathologic.

The Effect of X-ray Contrast Media on the Endothelium of the Aorta and Vena Cava in Rats

Using radiographic contrast media for aortography-, arteriography, and phlebography one must be aware of two complications due to contrast media: First, anaphylactoid reactions and second, local complications especially thrombosis. Endothelial damage produced by the contrast media is generally considered to be the primary cause of these complications [4]. The following factors contributing to the more harmful effects of contrast media on the endothelium are currently under discussion [5]; 1. The chemical structure of the medium 2. The cation component used in the making up of the solution 3. Details of administration, such as the temperature of the medium and the rapidity of the injection 4. The physicochemical properties of the solution such as Pk value, protein-binding capacity, lipophilia, and osmolality