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Arterial-wall tissue factors influencing haemocoagulation, and their release into circulation in endarterectomy.

The wall of lover-limb arteries affected with severe atherosclerosis contains a Complex of substances with pro- and anticoagulative activities. The arterial wall, traumatized in endarterectomy by separation of the individual coats, releases procoagulative substances into blood circulation. The most conspicuous local manifestations of hypercoagulation and hypofibrinolysis appear on the day of surgery. The artery operated upon releases the thromboplastic factor for nine days; substances shortening the thrombin time (antiheparin substance, thrombin accelerator), for five days; and inhibitors of fibrinolysis, for four days after operation. A correlation was found between the regenerative process in the endarterectomized artery and the dynamics of the release of tissue factors influencing the haemocoagulation.

Animals↗

The inhibition of cancer cell stickiness, a model for investigation of platelet aggregation inhibitors in vivo. Effect of the sulfonyl urea derivatives, glibenclamide, gliclazide, and HB180, as well as the carboxylic acid derivative, meglitinide.

Employing the test model which we developed for the investigation of platelet adhesiveness and aggregation in vivo, experiments demonstrated that the sulfonyl urea derivatives, glibenclamide, gliclazide, and HB 180, as well as the carboxylic acid derivative, meglitinide, are able to inhibit, in a dose-dependent relationship, the adherence of i.v. injected Walker-256-carcinosarcoma cells to the vascular endothelium of the rat mesentery, as well as to reduce significantly the rate of instantly occurring terminal tumor cell embolism of the lung. Since venous blood platelet count in surviving animals is inversely proportional to the number of the tumor cells which adhere to the vascular endothelium, one can deduce that tumor cell embolism is an immediate result of a massively occurring disseminated intravascular coagulation (DIC) which may be induced by i.v. injection of thromboplastic active carcinosarcoma cells and leads primarily to a drastic platelet count reduction. All four substances inhibit this platelet count reduction as well as the directly correlated tumor cell embolism mortality rate in a linear dose-dependent fashion. Their action can therefore be explained as being mediated via an inhibition of platelet adhesion and aggregation to the circulating tumor cells. Our proof of platelet aggregation in vivo correlates with the results obtained by Klaff et al. (1979), as far as a normalization of the pathologically increased platelet aggregation tendency in vitro in diabetics following 4-6 weeks of therapy with the sulfonyl urea derivatives glibenclamide and gliclazide.

Animals↗

The haemostatic system components of neointima forming in polyester aortic grafts in the early postoperative period.

The aim of the studies was to determine the content of certain components of the haemostatic system in the neointima of a polyester graft implanted in the dog abdominal aorta over a 7-day period of observation. The neointima of an aortic polyester graft in the early postoperative period possesses a high thromboplastic activity, greater than that of the artery or vein, and containing prothrombin, active thrombin, platelet aggregating substances and heparin neutralizing substances. The plasminogen activator activity in the neointima of the polyester graft is also considerably higher than in the intima of arteries and veins.

Animals↗

Isolation and characterization of bovine factor XI (plasma thromboplastin antecedent).

Factor XI (plasma thromboplastic antecedent) has been purified approximately 28 000-fold from bovine plasma with an overall yield of about 30%. The isolation procedure involves barium sulfate adsorption of contaminants, ammonium sulfate precipitation, and chromatography on heparin-agarose, CM-Sephadex, and DEAE-Sephadex. The final product was homogeneous when examined by polyacrylamide gel electrophoresis and immunoelectrophoresis. A minimal mol wt of 124 000 was determined by sedimentation equilibrium. Factor XI is composed of two similar or identical polypeptide chain (mol wt of approximately 55 000), and these two chains are held together by a disulfide bond(s). Factor XI is a glycoprotein which contains approximately 11% carbohydrate including 5.4% heose, 4.7% N-acetylhexosamine, and 1.0% N-acetylneuraminic acid. Other properties of this coagulation factor including its amino acid composition and inhibition by antibodies prepared in rabbits are also reported.

Amino Acids↗