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.

No abstract

Tracheostomies and Stroke

The mechanism responsible for the sticking of white blood cells to blood vessel walls in early inflammation continues to pose a challenging problem since this reaction represents the key to an overall understanding of the exudatire events set off by injury.In studies reported earlier, interference with the clotting of blood in vivo failed to prevent the vigorous sticking of leucocytes to vascular endothelium within rabbit ear chambers damaged by heat. As a specific example, maximal activation of the endogenous fibrinolytic system of rabbits by streptokinase (SK) administration did not diminish adherence of circulating white blood cells to endothelium. Since lysis of fibrin in vitro was brisk, failure to modify the sticking reaction could be explained only by assuming that destruction of fibrin on the surfaces of both white cells and endothelium failed to keep pace with newly formed material. 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.Such consistent failure to halt white cell sticking led to an investigation of specific pharmacological substances known to block the clotting of blood in vivo. From preliminary observations previously reported, it was anticipated that one such agent, heparin, would materially impede the reaction (2). Although many anticoagulants were available, heparin and warfarin sodium were selected because of extensive use by others; both were of low toxicity in the ranges used; and because each could be administered parenterally to insure adequate blood levels. Furthermore, both agents were known to prevent not only the local but also the generalized Shwartzman reac-*