Effect of Thorotrast on Reversible Hemorrhagic Skock

In previous publications we presented evidence that a bacterial endotoxin is present in the blood and tissues of the animal in hemorrhagic shock; and that if shock is sufficiently prolonged this endotoxin prevents a sustained response to infusion of all the blood removed, so that death follows soon thereafter (1, 2). Since the ingestion of circulating endotoxins, and, by inference, their detoxitication is achieved for the most part by the RES (3, 4), an examination of this system in hemorrhagic shock is in order. Some data on this subject are already in hand: (a) Macrophages from the peritoneal cavity of the normal animal exhibit a markedly lower phagocytic and bacteriostatic power in plasma from shocked animals than in plasma from normal animals (5). (b) Macrophages removed from the rabbit's peritoneal cavity 48 hours after transfusion for reversible hemorrhagic shock contain considerably less B glucuronidase and acid phosphatase than comparable macrophages harvested from unshocked rabbits (6). (c) Sensitivity to endotoxin is increased at least 100,000-fold in rabbits soon after exposure to hemorrhagic shock of short duration (7). Sensitivity to endotoxin is also increased in rats by blockade of the RES with particulate materials (8). (d) Tolerance of an otherwise lethal exposure to hemorrhagic shock in rabbits is produced as a result of repeated daily injections of a sublethal dose of endotoxin, given to enhance the RES's capacity to dispose of circulating endotoxin (9,10). Blockade of the RES abolishes the increased tolerance to shock in rats made resistant to endotoxin (8). (e) Rabbits exposed to 90 minutes of hemorrhagic shock are killed by a much smaller intravenous dose of dog or human plasma (free of hemagglutinins) than normal rabbits (11). In this communication additional data are presented showing a direct relationship between the functional status of the RES with respect to endotoxins and the tolerance of hemorrhagic shock.