Coronary thrombolysis with tissue-type plasminogen activator in patients with evolving myocardial infarction.

Tissue-type plasminogen activator is a naturally occurring, clot-selective activator of fibrinolysis. We recently reported that human tissue-type plasminogen activator isolated from a Bowes-melanoma-tissue-culture supernate lysed coronary thrombi in dogs without depleting circulating fibrinogen or alpha 2-antiplasmin, in contrast to the case with streptokinase and urokinase. In the present study coronary thrombolysis, confirmed angiographically, was induced within 19 to 50 minutes with intravenous or intracoronary tissue-type plasminogen activator in six of seven patients with evolving myocardial infarction.

Precapillary vessels and peripheral vascular ischemic disease.

The vast majority of patients with peripheral arterial insufficiency have degenerative lesions in large arteries; however, collateral circulation develops in smaller arteries and arterioles. Vascular disorders affecting arterioles are idiopathic Raynaud's disease and systemic sclerosis. The pathogenesis of Raynaud's phenomenon is still poorly understood.

Dipyridamole inhibits platelet aggregation in whole blood.

Dipyridamole possesses antithrombotic properties in the animal and in man but it does not inhibit platelet aggregation in plasma. We evaluated the effect of dipyridamole ex vivo and in vitro on platelet aggregation induced by collagen and adenosine-5'-diphosphate (ADP) in human whole blood with an impedance aggregometer. Two hundred mg dipyridamole induced a significant inhibition of both ADP- and collagen-induced aggregation in human blood samples taken 2 hr after oral drug intake.

Manipulation of the local thromboxane and prostacyclin balance in vivo by the antithrombotic compounds dazoxiben, acetylsalicylic acid and nafazatrom.

We have developed an experimental model for the study of local prostaglandin production by platelets and the vessel wall following stimulation 'in vivo'. A nylon thread was inserted into the external jugular vein of rabbits; its presence did not induce an occluding thrombus. Thromboxane (TXB2) values in the blood, sampled through the facial vein, immediately distal to the stimulus, rose and remained high for at least 4 hr, while 6-keto prostaglandin (PG) F1 alpha levels, after a first increase, gradually returned to normal ('exhaustion' of the endothelial cells?).

Transluminal angioplasty: late results sustained by digital intravenous subtraction angiography.

Digital intravenous subtraction angiography (DIVSA) appears to be a technique of minimal invasiveness and high accuracy in the follow-up of patients after percutaneous angioplasty (PTA) allowing correct angiographic evaluation in more than 96% of the cases. Correlation between clinical and angiographic findings seems to be excellent. Of the controlled intravenous examinations performed in 54 successful PTA procedures 75% appeared patent after 10 to 30 months, constituting 52% of the original attempts.

Thrombolysis with human extrinsic (tissue-type) plasminogen activator in rabbits with experimental jugular vein thrombosis. Effect of molecular form and dose of activator, age of the thrombus, and route of administration.

A simple venous thrombosis model in rabbits was used for the quantitative evaluation of the thrombolytic effect of human extrinsic (tissue-type) plasminogen activator as compared with urokinase.A thrombus was formed in an isolated segment of the jugular vein from a mixture of (125)I-labeled fibrinogen, whole rabbit blood, and thrombin. In order to immobilize the thrombus during lysis, it was formed around a woolen thread introduced longitudinally in the lumen of the vein.

A pharmacological approach to the inhibition of platelet adhesion and platelet aggregation. Wright-Schulte Lecture.

A first level of pharmacological interference with platelet function is located at the site of the agonist-receptor interaction (receptors for collagen, adenosine diphosphate, serotonin, fibrinogen). A second level of interaction is to prevent the mobilization of intracellular calcium ions which can be obtained by inhibition of phosphodiesterase, activation of cAMP (e.g.

[Problems and prospects for clinical heparin use].

The paper contains new data on the pharmacodynamics of heparin and its interaction with the Xa factor, antithrombin III and thrombin. A critical assessment of the clinical efficacy of different types of heparin treatment of thromboembolisms is given, including thromboembolism of the pulmonary artery.

Thromboxane synthetase inhibition as antithrombotic strategy.

The imidazole derivative UK-37 248, a thromboxane synthetase inhibitor, reduces the in-vitro formation of thromboxane B2 and hydroxyheptadecatrienoic acid by washed platelets, and this is compensated for by an increased production of prostaglandins E2 and F2 alpha; arachidonic acid challenged platelets pretreated with UK-37 248 also stimulate the production of prostacyclin by aspirin pretreated cultured endothelial cells. In a double-blind placebo controlled study to examine the in vivo properties of UK-37 248, human volunteers ingested 200 mg of the compound. Their serum thromboxane B2 levels dropped and their plasma 6-keto-prostaglandin F1 alpha values rose.