Studies on the Pathogenesis of Acute Inflammation

Abstract

The relation of intravascular fibrin to the leucocytic sticking reaction in ear chambers of rabbits injured by heat was investigated in two ways. First, attempts were made to destroy the thin layer of fibrin believed to coat the surfaces of cells involved in the sticking reaction. Second, white cell sticking was studied after fibrinogen had been removed from the blood stream. The results of these experiments were as follows:— 1. Activation of fibrinolysin in vivo by streptokinase did not impair sticking of white blood cells. 2. Administration of streptokinase parenterally did not lower fibrinogen blood levels appreciably even when the amount used was large. 3. Thromboplastin infusions alone reduced circulating fibrinogen to low levels but leucocytic sticking was not prevented. Furthermore, frequent death of animals due to pulmonary embolism made such experiments prohibitive. 4. Addition of streptokinase to thromboplastin infusions protected against embolic deaths but did not influence sticking even though the fibrinogen levels achieved were quite low. 5. Finally, when thrombin was added to infusions of thromboplastin and streptokinase, no circulating fibrinogen could be detected. Under such circumstances leucocytic sticking following heat injury occurred without reduction. These findings were interpreted as evidence against a primary role of the blood clotting mechanism in causing the sticking of white blood cells to injured endothelium. Alternative explanations were discussed.

Studies on the Pathogenesis of Acute Inflammation

“…It was found that the addition of thrombin to plasma obtained from animals after extended defibrinogenation produced a small amount of granular precipitate after the mixtures were allowed to stand at room temperature for 8 to 24 hours. Such prolonged incubation of thrombin with experimental plasma was not done in previous studies (1). Although a fibrin web did not form, this granular material suggested a clottable protein, perhaps an altered form of the fibrinogen-fibrin complex.…”

“…Warfarin sodium ~ (supplied as coumadin sodium) in bulk powdered form was prepared in concentrations of 30 mg/ml in sterile water for intravenous administration. Varidase, s data pertaining to enzyme content may be found with experiments, mixed in pyrogen-free 5 per cent dextrose in water (Baxter Laboratories) was administered by continuou s intravenous infusion at a rate of 25 ml per hour by a technique described earlier (1). Preparation and administration of both thromboplastin and thrombin were as noted before (1).…”

“…All substances for intravenous use were screened for content of bacterial pyrogens by methods described previously (1). Whenever possible, exceptions are noted in text, pyrogenic substances were avoided.…”

“…This was evident sometimes within 30 minutes and always by 1 or 2 hours after trauma and, as must be reemphasized, developed only within the immediate area of trauma. In damaged ear chambers of untreated rabbits, formation of platelet thrombi and the proliferation of fibrin strands is not a prominent finding but can be seen when searched for diligently (1,2). The first detectable change in the injured chamber after heparin had been given was an increased adhesiveness of platelets.…”

“…In a more direct approach to the problem, the behavior of white cells in damaged chambers was followed after removal of all chemically detectable fibrinogen from the systemic circulation. Even under these conditions, when fibrinogen levels were too low to measure, brisk leucocytic sticking still developed after ear chambers had been damaged by heat (1). From these data it was concluded that the sticking reaction was not causally related to formation of fibrin.…”