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The antiphospholipid antibody syndrome is an autoimmune disease which attracts in recent years increasingly the attention of angiologists and cardiologists. Although it is manifested as regards laboratory indicators as a circulating anticoagulant, somewhat paradoxically clinicians observe only a marked tendency towards venous and arterial thromboses at different sites. The condition is frequently encountered in young people with idiopathic and recurrent diseases. Laboratory diagnosis of the condition as well as new therapeutic possibilities are being developed.

Native heparin was very effective in models of arterial and venous thrombosis as well as in a model demonstrating the effect on endothelial stability in rats. The effect on venous thrombosis was particularly prominent. The activities of LMW-heparin were about the same in all three models, the absolute effective dose against arterial thrombosis being much lower than with native heparin. A heparan sulfate-related preparation (suleparoide) was much less effective in both thrombosis models, especially in the venous one, while the activity was most specifically directed to the maintenance of endothelial stability.

Clot adherence to peritoneal cavity mesothelium was studied in rats in an attempt to contribute to the problem of thrombus embolization. The adherence was decreased by platelets and the active constituent was identified as adenosine diphosphate which decreased the sticking of fibrin to cellular linings as well as to artificial surfaces.

A series of drugs representing several groups of antithrombotics was tested in a new model of arterial thrombosis in rats. Thrombosis was produced in the aorta by the combination of local partial obstruction and systemic administration of hypotonic saline with serotonin. High efficacy was demonstrated with heparin, acetylsalicylic acid, troxerutin, prenylamine, antiserotonin agents /pizotifen, ketanserin/ and particularly with the combinations of antiserotonins and the above mentioned antithrombotic drugs. The model showed high sensitivity to all tested drugs in the clinical dose range.

The model of arterial thrombosis in rats used in this study is especially suitable for testing the preventive effect of antithrombotic drugs. An oral anticoagulant was ineffective in this model. Heparin, streptokinase, acetylsalicylic acid and dipyridamole were only moderately effective whereas highest effectiveness was attained by combining heparin with acetylsalicylic acid.

In connection with the increasing importance of the endothelium in understanding the pathogenesis of vascular diseases, new types of mediators originating in the endothelium are described, such as EDRF and endothelin. The method of endothelial cell cultivation has contributed to their detection. Besides such analytical methods, a more global in vivo aspect of endothelial function is dealt with by the method of counting circulating endothelial cell carcasses in blood applicable also clinically. The increase of endothelaemia goes hand in hand with both the tendency to thrombosis and increased permeability. Similarly, the main atherosclerotic risk factors, smoking, hypertension and hypercholesterolaemia could be effective by producing an endothelial perturbation as indicated by increased endothelaemia.

Two highly sensitive models of arterial and venous thrombosis forming with the test of endothelial stability a complementary system with a maximum stress on the role of vascular lesion were used to test a series of four antithrombotic drugs (heparin, acetylsalicylic acid, dipyridamole, sulfinpyrazone) and four drugs with other indications but with an antithrombotic activity in experiment (prenylamine, troxerutin, ketanserin and pizotifen). All drugs, except heparin, were given orally. Whereas heparin, aspirin and prenylamine had mixed effects on both arterial thrombosis (i.e. mostly on platelet functions) as well as on endothelial stability, ketanserin and pizotifen had a predominant effect on the former while dipyridamole, troxerutin and sulfinpyrazone influenced mostly the latter function.

A critical review is presented on animal models of thrombosis. After a glance at the pathogenesis of clinical thrombosis and its multifactorial character, the classification, aims and a suggested rational design of thrombosis models are advanced and illustrated by some examples of an attempted solution of this complex problem.

A single intravenous injection of homocystine led to an increase in the number of circulating endothelial cells in the blood of rats. We observed also increased permeability of the lung capillaries, platelet sequestration and activation of the venostatic thrombosis. Endothelial injury is probably the key mechanism of thrombotic and atherosclerotic complications in homocystinuria, an inborn error of the amino acid metabolism.

A new model of arterial thrombosis in rats was based on a combination of a localizing hemodynamic factor /partial mechanical constriction of aorta/, generalized mild endothelial lesion /i.v.hypotonic saline/ and a humoral factor/i.v. serotonin/. The resulting aortic occlusion was indicated by measuring rectal temperature. Nicotine and oral methionine were similarly active as hypotonic saline. Histamine had to some extent similar activity as serotonin. The possible contribution of serotonin vasoactivity to the vascular obstruction was contradicted.

In the rat, a selection of two experimental models of "prethrombotic states", one of venostatic thrombosis and one of arterial thrombosis was used to compare the antithrombotic of three flavonoid preparations: O,-(beta-hydroxyethyl)-rutosides (HR), an association of trihydroxyethylrutoside and coumarin (troxerutin) and 7-mono-hydroxyethylrutoside (7-Mono-HR), as well as acetylsalicylic acid (ASA). The flavonoids were very effective "protectors" on the prethrombotic models, but only ASA was active on the model of arterial thrombosis. No compound showed a clear protection on the venostatic model if direct activation by kaolin was used. However, if an indirect activation by vessel wall stimulation was used, 7-Mono-HR possessed a marked protective effect. The most favourable results were obtained with an association of 7-Mono-HR and ASA, which could be considered for investigation in clinical thrombosis prophylaxis.

A series of standardized thrombosis models in rats has been used to survey some most important groups of antithrombotics. Most results confirmed the previous clinical and experimental experience but some of them bring new evidence. Very effective from this aspect appear to be dipyridamole, low-molecular weight dextran and flavonoids. Particularly favourable was the effect of the combination of flavonoids and acetylsalicylic acid which eliminates some untoward effects of the latter drug.

Flunarizine in vivo protects against endothelial cell damage induced by intravenous injection of citrate, CaCl2, or lactate in rats. Its effect is optimal at the low oral dose of 0.1 mg/kg, corresponding to the clinically used one. It lasts for at least 8 hours. Edema formation, platelet activation, and venostatic thrombosis subsequent to endothelial cell injury consequently are also inhibited by flunarizine. The compound does not affect platelet function, plasma coagulation or generation of PGI2 by vascular tissue and does not impair normal haemostasis at effective doses. As for its vascular and hemorrheological effects, the protection by flunarizine against endothelial injury may be related to its Ca2+-antagonistic properties. [ABSTRACT FROM AUTHOR]