The in vitro effect of Ateroid® on the fibrinolytic activity of rat euglobulins

SummaryTissue plasminogen activator labeled with radioactive iodine (125I-tPA) was immobilized on vascular prostheses chemically modified with a thin coating of water-insoluble surfactant, tridodecylmethylammonium chloride (TDM AC). Surfactant- treated Dacron, polytetrafluoroethylene (PTFE), silastic, polyethylene and polyurethane bound appreciable amounts of 125I- tPA (5-30 μg 125I-tPA/cm2). Upon exposure to human plasma, the amount of 125I-tPA bound to the surface shows an initial drop during the first hour of incubation, followed by a slower, roughly exponential release with a t½ of appoximately 75 hours. Prostheses containing bound tPA show fibrinolytic activity as measured both by lysis of clots formed in vitro, and by hydrolysis of a synthetic polypeptide substrate. Prior to incubation in plasma, tPA bound to a polymer surface has an enzymic activity similar, if not identical to that of the native enzyme in buffered solution. However, exposure to plasma causes a decrease in the fibrinolytic activity of both bound tPA and enzyme released from the surface of the polymer. These data demonstrate that surfactant-treated prostheses can bind tPA, and that these chemically modified devices can act as a slow-release drug delivery system with the potential for reducing prosthesis-induced thromboembolism.

Download Full-text

Gastric Fibrinolysis

Thrombosis and Haemostasis ◽

10.1055/s-0038-1651400 ◽

1975 ◽

Vol 34 (02) ◽

pp. 409-418 ◽

Cited By ~ 9

Author(s):

I. M Nilsson ◽

S.-E Bergentz ◽

U Hedner ◽

K Kullenberg

Keyword(s):

Gastric Ulcer ◽

Gastric Juice ◽

High Activity ◽

Fibrinolytic Activity ◽

Duodenal Juice ◽

Bleeding Tendency ◽

Local Fibrinolysis ◽

Heated Plates

SummaryGastric juice from 15 normals, 20 patients with gastric ulcer and 4 patients with erosive haemorrhagic gastroduodenitis was investigated in respect of its activity on unheated and heated fibrin plates and its content of FDP and plasminogen or plasmin with immunochemical methods. Gastric juice from normals showed no activity on unheated and heated fibrin plates, and no FDP or plasminogen could be demonstrated. In the patients with gastric ulcer the gastric juice showed little or no fibrinolytic activity on fibrin plates except in 2, who had regurgitation of duodenal juice and neutral pH of the juice. These patients had equally high activity on heated as on unheated plates and no plasmin could be demonstrated. It was shown that this activity was not due to fibrinolysis, but to non-specific proteolytic activity (probably trypsin). The patients with erosive haemorrhagic gastroduodenitis exhibited quite a different picture. The gastric juice from these patients showed extremely high activity on fibrin plates, the activity was higher on unheated than on heated plates. The activity was inhibited in vitro by addition of EACA and in vivo after administration of AMCA. The occurrence of plasmin could be demonstrated directly immunologically in the gastric juice. By comparison of plasmin and trypsin in various assays it could further be proved that the gastric juice in these cases contained plasminogen activator and plasmin. The patients with erosive haemorrhagic gastroduodenitis showed no increase in fibrinolysis in the blood, but low values for plasminogen and α2M, and the serum contained FDP. These findings in the blood and gastric juice were interpreted as signs of local fibrinolysis in the stomach and duodenum. There is reason to assume that this gastric fibrinolysis contributes substantially to the bleeding tendency. The effect of administration of AMCA on fibrinolytic activity and the haemorrhage lends support to the assumption of such a mechanism.

Download Full-text

A Comparative Ex Vivo Study of Plasminogen Activators and Proteases for Fibrinolytic Activity and Side Effects in Rabbits

Thrombosis and Haemostasis ◽

10.1055/s-0038-1649213 ◽

1977 ◽

Vol 37 (01) ◽

pp. 154-161 ◽

Cited By ~ 1

Author(s):

B. A Janik ◽

S. E Papaioannou

Keyword(s):

Side Effects ◽

Effective Dose ◽

Fibrinolytic Activity ◽

Ex Vivo ◽

Plasminogen Activators ◽

Assay System ◽

Coagulation Parameters ◽

Ex Vivo Assay

SummaryUrokinase, streptokinase, Brinase, trypsin, and SN 687, a bacterial exoprotease, have been evaluated in an ex vivo assay system. These enzymes were injected into rabbits and the fibrinolytic activity as well as other coagulation parameters were measured by in vitro techniques. Dose-response correlations have been made using the euglobulin lysis time as a measure of fibrinolytic activity and the 50% effective dose has been determined for each enzyme. Loading doses, equal to four times the 50% effective dose, were administered to monitor potential toxicity revealing that Brinase, trypsin, and SN 687 were very toxic at this concentration.Having established the 50% effective dose for each enzyme, further testing was conducted where relevant fibrinolytic and coagulation parameters were measured for up to two days following a 50% effective dose bolus injection of each enzyme. Our results have demonstrated that urokinase and streptokinase are plasminogen activators specifically activating the rabbit fibrinolytic system while Brinase, trypsin and SN 687 increase the general proteolytic activity in vivo.The advantages of this ex vivo assay system for evaluating relative fibrinolytic potencies and side effects for plasminogen activators and fibrinolytic proteases have been discussed.

Download Full-text

Evaluation of a New Preparation of Urokinase

Thrombosis and Haemostasis ◽

10.1055/s-0038-1649107 ◽

1973 ◽

Vol 30 (01) ◽

pp. 114-122

Author(s):

C.R.M Prentice ◽

K.M Rogers ◽

G.P McNicol

Keyword(s):

Body Weight ◽

Maintenance Therapy ◽

Initial Dose ◽

Fibrinolytic Activity ◽

Pharmacological Effect ◽

Whole Body ◽

Fibrinolytic Agent ◽

Thromboplastic Activity

SummaryThe pharmacological effect of a new preparation of urokinase (Leo) has been studied, both in vitro and in six patients suffering from thrombo-embolic disorders. It was a non-toxic, effective fibrinolytic agent if given in sufficient dosage. A regimen consisting of an initial dose of 7,200 ploug units per kg body weight, followed by hourly maintenance therapy with 3,600 ploug units per kg intravenously, gave satisfactory evidence of whole body fibrinolytic activity. The preparation had minor but insignificant thromboplastic activity both when assayed in the laboratory and when given to patients.

Download Full-text

The Effects of Some Synthetic Compounds on In Vitro Fibrinolytic Activity Measured by Different Methods and the Relevance to Activity In Vivo

Thrombosis and Haemostasis ◽

10.1055/s-0038-1649018 ◽

1972 ◽

Vol 28 (03) ◽

pp. 351-358

Author(s):

A.J Baillie ◽

A. K Sim

Keyword(s):

Inhibitory Activity ◽

Substrate Concentration ◽

Fibrinolytic Activity ◽

Synthetic Compounds ◽

In Vitro Methods ◽

Narrow Concentration Range

SummaryThe activity of several synthetic compounds, rated from good to poor (or inactive) fibrinolytic activators, has been assessed by two different commonly-used in vitro methods. Compounds shown to be active over a narrow concentration range in the hanging clot test were shown to be inhibitors of plasmin and trypsin in the casein-olytic test. The inhibitory activity of these compounds was shown to increase with increasing substrate concentration and apparent activity in the hanging clot test. Possible explanations and relevance of these observations are discussed.

Download Full-text

Persistence of Fibrinolytic Activity in Fragments of Human Veins Cultured in Vitro

Thrombosis and Haemostasis ◽

10.1055/s-0038-1654209 ◽

1970 ◽

Vol 24 (01/02) ◽

pp. 043-047 ◽

Cited By ~ 4

Author(s):

M Pandolfi

Keyword(s):

Blood Vessels ◽

Plasminogen Activator ◽

Fibrinolytic Activity ◽

Vasa Vasorum ◽

Adult Human ◽

Slide Technique

SummaryExplants from 5 adult human veins were cultured in a fibrinolytically inactive medium for 3 weeks and assayed for the presence of plasminogen activator by the fibrin slide technique. The explants from 3 veins showed fibrinolytic activity confined to their vasa vasorum for the whole duration of the culture; no decrease of activity was seen. The finding suggests that small blood vessels are able to synthesize plasminogen activator.

Download Full-text