Abstract
Summary
1. Lethal shock was established with a standardized dose of E. coli endotoxin in adult mongrel dogs. In this species initiation of the peripheral vascular collapse involves liberation of histamine, which may be related to the activation of a proteolytic system by the endotoxin. 2. Pre-treatment of dogs with epsilon-aminocaproic acid (EACA), a potent inhibitor of plasminogen activator, protected the majority of animals against a lethal dose of endotoxin. Protection was also observed when EACA was given up to 30 minutes after injection of endotoxin. However, when EACA was administered beyond this time no protection occurred, and there was no evidence that the severity of the shock was modified. It is emphasized that these observations with EACA apply only to the dog. 3. The primary purpose of the present experiments was to determine if EACA protected dogs against lethal amounts of endotoxin. The results do not permit the conclusion that EACA modified the severity of shock by blocking plasminogen activation, and in this manner prevented liberation of histamine. There remains the possibility EACA blocked proteolytic activity that is independent of the plasminogen-plasmin system.
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