108 FIBRINOLYSIS

274 In vivo modulation of fibrinolysis: effects of dexamethasone and retinoic acid JANSEN JWCM, VAN GIEZEN JJJ Duphar B. K, Depamnent of Pharmacology, Weesp, l%e Netherlands

The fibrinolytic system is of essential importance in the maintenance of the haemostatic balance. Pathological con- ditions as cardiovascular disease are frequently associated with a lowered fibrinolytic potential (Kruithof et al. 1988). Modulation towards normal levels of those components which determine the fibrinolytic capacity is therefore a real basis for the development of antithrombotics. We report here the in vivo modulatory effects of dexamethasone and retinoic acid. Dexamethasone or retinoic acid were admin- istered p.o. twice daily to male Wistar rats for a period of 4 days. Dexamethasone treatment (0.1-3 mg/kg) resulted in a

decreased fibrinolytic potential as measuredwith the diluted blood clot lysis test (DBCLT). At 1 mg/kg lysis was decreased by 40%. Insertion of a wire in the vena cava of rats, treated with the same dose schedule, resulted in an increased size of the formed thrombus (at 1 mg/kg: 50% increase). Administration of retinoic acid (0.3-3 mg/kg) to rats resulted in increased lysis rates (DBCLT assay): 40% increase at 1 mg/kg. In the wire model retinoic acid admin- istration resulted in a 35% decrease of the formed thrombus. These results indicate that it is possible to modulate the fibrinolytic system in vivo. The results also suggest that venous thrombosis is directly dependent on the fibrinolytic potential.

275 Fibrinolysis in experimental atherosclerosis in rabbits LYAPINA LA, PASTOROVA VE, KONDASHEVSK4YA

tally lowered fibrin-depolymerizing activity concomitant with the low level of nonenzymatic fibrinolysis in blood plasma may be regarded as diagnostic criteria of the pre- thrombotic state.

School of Biology, Moscow State University, Moscow, USSR

The degree of polymerization of non-stabilized fibrin, total fibrinolysis and activity of the antithrombin III-heparin com- plex have been studied in the blood plasma of rabbits kept on an atherogenic diet over a period of 2 months. These studies revealed a weak fibrin-depolymerizing activity which made up to 23% (cf. 49% in the norm) and a low level of total fibrinolysis and heparin-dependent nonenzymatic fi- brinolytic activity. It was found also that the activity of the antithrombin III-heparin complex and the time of free thrombin formation are decreased. Thus, apart from the well-established signs of prethrombosis the decreased activ- ity of the antithrombin III-heparin complex and the drasti-

276 Evaluation of coagulative and fibrinolytic uated whether high t-PA or U-PA plasma levels could pro- parameters in plasma obtained from corpus duce the fibrinolytic activity in this district. FPLA obtained kavernosum dking therapy-induced erection from plasma incubated with polyclonal anti-t-PA did not

BAZZAN M, *ROLLE L, TAMPON G, *FONTANA D decrease: we conclude that fibrinolysis in this district is not

Divkione Universitaria di Ematolonia dell’osu. S. Giovanni related to high t-PA plasma levels.

Bat&a, Torino e *Divisione Univektaria di Urologia dell’osp. S. Luigi, Orbassano - Italia

Coagulative and fibrinolytic parameters were evaluated in 15 patients with andrological disfunctions; blood was ob- tained from corpus cavernosum during papaverin-induced erection for urologic test or therapeutic purpose. We de- monstrated a significant increase in fibrinolytic activity in the corpora cavernosa of all these patients during erection, mean FPLA (fibrin plate lysis area) being 277+83 mm2 in corpus cavernosum versus 852 15 in peripheral venous blood (pcO.001). PT, P’IT and fibrinogen were not differ- ent with respect to venous peripheral blood. Then we eval-