Effect of Induced Chronic Intravascular Coagulation on Plasminogen Activator in Dogs

Abstract

SummaryPlasminogen activator activity in blood vessels of various organs was determined in three untreated (control) male dogs and in two male dogs that received a continuous infusion of canine brain thromboplastic emulsion for 2 weeks. Activator was measured by the speed and degree of lysis of fibrin films that were overlaid with slices of tissue. Depletion of vascular plasminogen activator occurred in the vena cava of treated dogs at the site of the tip of the catheter, which was surrounded by a clot. A decrease of activator was found in most organs and particularly in certain endocrine organs (thyroid, pituitary, and testis). Of organs that normally contained the most activator, the greatest depletion was found in the skin, lung, and penis. The wide variation of plasminogen activator activity in organs of normal dogs is described.

The Turnover in Normal Dogs of Prothrombin and Its Fragments; Effect of Induced Intravascular Coagulation

“…It was somewhat surprising to us to find no significant increase in the plasma catabolic rate of prothrombin during infusion of thromboplastin into dogs. However, a previous study from this laboratory reported that during such infusions only slight to modest reductions in the plasma concentration of prothrombin occur (Cooper et al 1973, Owen and Bowie 1974, Sun et al 1974, Owen and Bowie 1975. The failure of these levels to decline may indicate that only a small amount of prothrombin is converted to thrombin by thromboplastin in vivo or that hepatic synthesis of prothrombin keeps pace with accelerated degradation.…”

“…Three other dogs were given labeled prothrombin 5, 6 and 8 days after the onset of a continuous infusion of a dog brain thromboplastic emulsion. Details of the induction of chronic intravascular clotting in the dog have been fully described (Cooper et al 1971, Owen et al 1973, Fuster et al 1974a, b, Owen and Bowie 1974, Sun et al 1974, Owen et al 1975, Owen and Bowie 1978. Once the fibrinogen level and platelet counts seemed stabilized, the labeled prothrombin was injected and the infusion of thromboplastin continued to the end of the study.…”

Disseminated Intravascular Coagulation: Evaluation of Therapeutic Approaches

“…Secondary fibrinolytic activation is one of the decisive compensating mechanisms by which the organism can remove microthromboses initiated by DIC. During the intravascular coagulation process, plasminogen activator is decreased [153]. Inhibitors of the fibrinolytic system have been found to be elevated in numerous diseases, and their possible role in the genesis of thrombotic disease has been suggested.…”

“…By virtue of its properties as an inhibitor of plasminogen activation, EACA is a potent antifibrinolytic agent which is used to control local bleeding due to increased fibrinolytic activity within particular tissues [2,125]. Release of activator activity from endothelium, induced by hypoxia and microthrombosis, accounts for the local activation of plasminogen which is coprecipitated with the fibrin thrombi, thus giving rise to secondary fibrinolysis [142,153]. All animal experiments designed to investigate the pathophysiologic aspects of DIC confirm that the administration of EACA results in considerable enhancement of microthrombosis, regardless of whether fibrin was precipitated by thrombin or by nonenzymatic mechanisms [7,52,115,120].…”

Fibrinolysis and Trauma

“…The lung is a target organ for microemboli [42] and thromboemboli are known to interfere with the fibrinolytic activity [47]. Chronic infusion of thromboplastic substances can decrease the plasminogen activator activity in the lungs and many other organs [45]. However, other mechanisms, such as neural are also possible.…”