Two or three spaced injections of endotoxin, given at 2 or 4 hour intervals to nonpregnant, normolipaemic rats, resulted in a decrease of the coagulability of blood associated with fibrin deposition in the liver and lung. In two series of experiments it was shown that an optimal dose of endotoxin exists for the production of stainable fibrin in liver veins and sinusoids, in the lungs, and, in particular, for the production of thrombopenia. Lower and higher doses of endotoxin did not lead to the same extent of thrombopenia. In contrast, the fibrinolytic activity of the lungs decreased in proportion to the increase in the doses of endotoxin. There were signs of increased activity of lysosomal enzymes of the reticular endothelial system after administration of both small and large doses of endotoxin.

The effect of 0.5 mg Ouabain (O) i.v. on sinus node function and on intracardiac conduction was studied by His bundle electrography and atrial stimulation. 7 patients with normal sinus node function and av conduction (group I), 5 patients with sick sinus syndrome (group II), and 5 patients with av block of changing degree (group III) were examined. 2 additional patients had simultaneous sinus node dysfunction and av block (group II/III). The sinus node recovery time was prolonged in 6 patients, the av block was located proximal to the His bundle in 4 patients and distal to the His bundle in 3 patients. The spontaneous sinus rate decreased in group I and remained unchanged in group II and III after O. The PA interval increased slightly after O in groups II and III, the AH interval during sinus rhythm was prolonged after O in groups II and III and in the whole group together. During atrial pacing, the stimulus-His-time was increased in each group when compared at identical stimulation rates. In 4 of 7 patients av block type Wenckebach appeared at a lower stilmulation rate after O. The HV interval remained unaltered after O, the sinus node recovery time varied after O. Phenytoin had no positive effect on the changes observed after O. Unwanted actions of O such as increased bradycardia or increased av conduction disturbances were not observed. O appears to be reasonably safe in most patients with sick-sinus syndrome and changing av block.

106 episodes of ventricular fibrillation were observed in 11 patients, 9 of whom had acute myocardial infarctions. The heart rate before the onset of ventricular fibrillation was below 50 in two episodes, 60 to 100 in 63, and above 100 in 41. 83 attacks of ventricular fibrillation were preceded by fewer than five ventricular premature beats, 23 by more than five, 19 by more than ten. Multifocal ventricular premature beats occurred ten times, runs of ventricular premature beats 11 times, with only three falling into the vulnerable period. Left bundle branch block was present in three patients, right bundle branch block with left anterior hemiblock in two, isolated left anterior hemiblock in two, left posterior hemiblock in one. 85 episodes of ventricular fibrillation occurred during antiarrhythmic treatment, 72 during lidocaine administration. Antiarrhythmic drugs were effective only in reducing the number of ventricular premature beats. The only successful treatment of recurrent episodes of ventricular fibrillation was repeated electrical countershocks.

Summary The plasminogen activator of the Arteria tibialis posterior of 8 patients with occlusive arterial diseases of the leg was determined in comparison to the plasminogen activator of normal subjects. The histochemical method of Todd (15) was used. The plasminogen activator of the pathological adventitia and the intima was significantly decreased. An impaired fibrinolytic system seems to be one of the important factors of atherogenesis. It could at least explain the frequent incidence of thrombotic complications.

On 10 patients with primary “carbohydrate-induced” hypertriglyceridemia (PCH), and 10 patients with atherosclerotic arterial diseases (AD) but without PCH, platelet adhesiveness was measured before and after venous congestion (as a thrombogenic state) in comparison with 10 normal subjects. Hellem's and Salzman's modified methods23,44 were used in a combined way. Platelet counts in patients with PCH were significantly lower than in both other groups. This may be due to an increased platelet “fragility” in patients with PCH. In all three groups platelet adhesiveness after venous congestion was 2-fold higher than before. The cause of this phenomenon is discussed. In all three groups no significant difference in platelet adhesiveness was found either before or after venous congestion. The investigations were performed on venous blood, and no conclusion is possible on platelet properties in arteries.

Blutungen im urologischen Bereich ohne lokal nachweisbare Ursache sind meist die Folge einer hämorrhagischen Diathese. Unter ihnen hat die Fibrinolyseaktivierung als pathophysiologísche Ursache besondere Bedeutung erlangt. Die Organe des Harntraktes sind reich an Gewebsaktivatoren, die bei Gewebsläsionen in das Blut gelangen und zu einer Fibrinolyseaktivierung führen, die oft heftige Blutungen auslösen kann. Gleichzeitig enthält gerade die Prostata dazu noch thromboplastische Substanzen, die die Gerinnung des Blutes aktivíeren und thromboembolische Komplikationen verursachen können. So ist oft als Blutungsursache neben der pathologischen Fibrinolyse auch eine Verbrauchskoagulopathie vorhanden. Im Harn selbst befindet sich als direkter Aktivator der Fibrinolyse die Urokinase. Solche Blutungen treten besonders nach der Operation einer benignen Prostatahypertrophie auf, bei Neoplasien des Harntraktes, etwa beim Prostatakarzinom, und bei der «Essentiellen Hämaturie». Gerinnungsbestimmungen und Fibrinolyseprüfungen aus Blut und Harn ermöglichen meist die Fest-stellung der Fibrinolyseaktivierung beziehungsweise auch die Diagnose einer Verbrauchskoagulopathie. Die Therapie besteht bei der Verbrauchskoagulopathie mit reaktiver Fibrinolyseaktivierung in einer kombinierten Therapie mit Antifibrinolytika wie EACS, AMCA oder PAMBA und Heparin oder Trasylol, bei primärer Fibrinolyseaktivierung mit Antifibrinolytika allein. Fallvorweisungen unterstreichen die Problematik von Diagnose und Therapie.

SummaryThe fibrinolytic activity respectively the PA activity of normal veins before and after venous occlusion is measured by the histochemical method of Todd. The results show marked decreases of PA of the adventitia and an increase of PA of the endothelial type, after venous occlusion. This suggests a transfer of PA through the venous wall into the intravascular lumen, and may be the cause of increased fibrinolytic activity in venous blood after occlusion. Contrary assumptions are discussed.

Zusammenfassung1. Zwischen PA. und Plasminogenspiegel besteht eine strenge Korrelation. Unter Annahme der Theorie der PA.-Plasminogeneinheit kann diejenige Plasminogenmenge, die nach Aktivierung zu Plasmin in einem kaseinolytischen System eine RCE ergibt, bei vollständiger Umwandlung durch Streptokinase im Überschuß in den Aktivator in der Stunde die 1026fache Menge Plasminogen zu Plasmin aktivieren.2. Unter »Normalbedingungen« ist der PA.-Spiegel der Aktivatoraktivität indirekt proportional, es scheint daher wahrscheinlich, daß bei der Blutaktivatorbildung PA. verbraucht wird.3. Bei Einschwemmung von Gewebsaktivatoren bzw. Steigerung der fibrinolyti- schen Aktivität durch Adrenalin und Venenokklusion gilt diese Korrelation nicht mehr, die Plasminogenaktivierung scheint hier über einen anderen Mechanismus abzulaufen.4. Zwischen PA. und Plasmafibrinogen besteht eine nicht sehr enge Beziehung.