Role of heparin in realization of the hypoglycaemic action of insulin.

A temporary resistance to the hypoglycaemic action of insulin has been found after preliminary binding of heparin in the blood of animals by 1 mg/200 of protamine sulphate (PS). This effect was observed after 5-30 min PS treatment before the insulin injection or endogenous increase of insulin stimulated by sugar load. PS did not influence the concentration of immunoreactive insulin in blood plasma. 2,5-ionene, a synthetic antagonist of heparin, induced temporary resistance to the hypoglycaemic action of insulin. Intravenous injection of heparin in corresponding doses after PS administration restored the hypoglycaemic effect of insulin. The results suggest that the presence in the circulation of reactive heparin may be necessary for insulin reception by the target tissue.

Anticoagulating and non-enzymatic fibrinolytic activities of heparin-antithrombin III and antithrombin III-heparin-thrombin complexes in vitro and in vivo.

The heparin-antithrombin III and antithrombin III-heparin-thrombin complexes were prepared in vitro. The formation of complexes was controlled by crossed electrophoretic and spectrophotometric methods. All the binary and ternary complexes prepared at the weight ratio of components 1: 1: 1 and at some other weight correlations were active as non-crosslinked fibrin solvents and kept this activity in the presence of inhibitors of plasmin fibrinolysis. A considerable prolongation of thrombin time and an increasing of total and in particular non-enzymatic lytic actions of plasma were achieved in 7 and 30 min after intravenous injection of 1 ml 0.1-0.2% solution of heparin-antithrombin III complex in rats. The obtained results of experiments allow to conclude that the heparin-antithrombin III and antithrombin III-heparin-thrombin complexes possess the non-enzymatic fibrinolytic action on non-crosslinked fibrin. The degree of this activity is dependent on the quantitative correlation of heparin-antithrombin III or antithrombin III-heparin-thrombin concentrations during the reaction of complex formation.

Role of macromolecular binding site of thrombin molecule in excitation of anticoagulation system.

The reaction of anticoagulation system upon perfusion of humorally isolated (with retained innervation) carotid sinus of a rabbit by alpha-,beta/gamma-, DIP-alpha-thrombin and prethrombin I was studied. DIP-alpha-thrombin without clotting activity was shown to initiate like alpha-thrombin the reflex reaction of anticoagulation system characterized by a sharp increase in non-enzymatic fibrinolysis (by 225%) and total fibrinolytic activity of blood (by 51%). Prethrombin I (thrombin precursor) is also capable of exciting the function of anticoagulation system characterized by an increase in non-enzymatic fibrinolysis (by 82%) and total fibrinolytic activity (by 36%). Furthermore, perfusion of prethrombin I or alpha-thrombin at almost the same molar concentrations resulted in the similar degree of anticoagulation system effector reaction. Reflex response of anticoagulation system was not observed upon perfusion of carotid sinus by beta/gamma-thrombin that has high esterase but little if any clotting activity that appears to be due to molecular changes in the macromolecular binding site region. These data support the suggestion that the effect of anticoagulation system excitation is due to interaction of the macromolecular binding site in the structure of alpha-thrombin with anticoagulation system chemoreceptors.

[Electronmicroscopic study on the molecular shape of non-stabilized fibrin break-down products produced by complex heparin compounds]. / Elektronenmikroskopische Untersuchung der Molekülformen von Spaltprodukten nichtstabilisierten Fibrins durch komplexe Heparinverbindungen.

Experimental data indicate that products develop from non-stabilized fibrin because of nonfermentative splitting by complex heparin connections. These products have a globular form with a diameter of 10-250 A and are similar to morphological fibrinogen molecules. The identified products show no marked lytic effect towards non-stabilized fibrin. The application of S35 labelled heparin in combination with preparative ultracentrifugation and electron microscopy enabled the determination to be established that heparin complexes will combine with particles of fibrinomeres, thus causing their transfer from the fibrillary to the globular condition. The destruction of the connections of heparin complexes with their globular molecule structures of fibrinmonomere, e.g. by protamine sulfate, guarantees their development and primary polymerization. With factor XIIIa being present, the structurally reconstructed fibrin will form a stabilized coagulum of full value which is similar in its ultrastructure to fibrin obtained in control tests.

[Participation of the hypophyseal-adrenal cortex system in thrombin clearance during immobilization stress]. / Beteiligung des Hypophysen-Nebennierenrinden-Systems an der Thrombinclearance beim Immobilisations-Stress.

The examination carried out with thrombin marked by 131J resulted in a considerable increase of the thrombin clearance rate in healty male rats during the stress (caused by an immobilization lasting 30 minutes) and in an increase of thrombin deposits in the liver. A further increase of thrombin clearance occurred by the combination of immobilization and administration of ACTH. Contrary to ACTH the thrombin clearance is not stimulated in healthy animals by hydrocortisone. Thrombin clearance and thrombin deposits in the liver are lowered in adrenalectomized rats. In these animals the administration of ACTH does not result in an increase of thrombin clearance. The rate of thrombin clearance is normalized in adrenalectomized animals after administering hydrocortisone without as well as under conditions of stress. In adrenalectomized animals having received hydrocortisone as well as in healthy animals the administration of ACTH will results in an increase of thrombin clearance. From these experiments the conclusion can be drawn that ACTH will increase the intensity of thrombin clearance in stress and that hydrocortisone plays a transmitting part here.

[The reactivity of the anticoagulatory system in sympathectomized animals under stress conditions due to acoustic trauma]. / Die Reaktivität des antikoagulatorischen Systems desympathisierter Tiere unter den Bedingungen eines durch akustische Reizung hervorgerufenen Stress

In rats of kind of Kruschinskij-Molodkina the number of cells in the stellate ganglion was diminished to 0.5% of the norm after eliminating the sympathetic tonus by means of guanethidine. These animals died of cardiac thrombosis during stress situations. This thrombosis cannot be explained by adrenalin, corticosteroids or thromboplastin spreading in the blood stream. A factor, the nature of which has still to be explained, may be assumed to be responsible for thrombosis to develop during stress situations in animals whose sympathetic tonus has been eliminated by guanethidine.

[Fibrinolytic properties of a heparin-ocrase complex]. / Uber fibrinolytische Eigenschaften eines Heparin-Ocrase-Komplexes

The obtained heparin-ocrase complex includes properties of inhibiting coagulation and a high fibrinolytic activity in vitro and in vivo. The fibrinolytic activity of the heparin-ocrase complex is higher than the equivalent amount of ocrase. The fibrinolytic activity of the complex is not only evident on non-stabilized fibrin plates, but likewise on stabilized ones and at the presence of inhibitors of enzymatic fibrinolysis, such as Trasylol and epsilon-aminocaproic acid. The complex formation between heparin and protease was confirmed by means of cross-paper electrophoresis and spectrophotometry.

[Complex compounds of heparin in obstetric hemorrhages]. / Kompleksnye soedineniia geparina pri akusherskikh krovotecheniiakh

The so-called uncontrollable hemorrhage in obstetric patients correlated mainly with appearance in blood of complex heparin compounds, primarily fibrinogen-heparin, adrenaline-heparin, noradrenaline-heparin and, less frequently, plasminogen-heparin. The heparin complexes were observed in circulation when the anticoagulation system was stimulated due to appearance of thrombin in the blood stream. The complexes possessed and anticoagulation and antipolymerization effects on fibrin-monomer and caused nonenzymatic lysis of unstabilized fibrin clots.