The early hemodynamic changes associated with the syndrome referred to as Gramnegative bacteremic shock continues to be an elusive medical problem (1, 6, 10). Of particular concern has been a definition of the exact mechanims by which this form of shock is set into motion (3,9,11). Early cardiovascular changes have been noted which appear to follow the release of neurohumeral agents into the blood stream (1, 2, 5 , 9 ) . Vasoactive materials such as histamine, serotonin, bradykinin, and the catecholamines have all been implicated as being involved in the earlier phases of endotoxin shock ( 2 , 3,5,9). Reports are conflicting, however, and no clear-cut delineation has been made as to which of these substances, if any, is involved in endotoxin shock. All things considered, however, many workers have concerned themselves with the role of histamine or a histamine-like substance in the very early stage of endotoxin shock (2, 7, It is the purpose of this study, therefore, to investigate the role of histamine in early endotoxin shock and to define its relationship to the fall in arterial blood pressure and to the sometimes lethal outcome so often associated with this form of stress.
Materials and Methods. A series of 22adult beagle dogs anesthetized with pentobarbitol sodium (30 mg/kg) was used in this study. Heart rate, EKG, respiratory rate, and blood pressure were continuously monitored on a Sanborn polygraph. I n addition, a large bore polyethylene catheter was placed in the femoral artery and advanced into the abdominal aorta to allow for the rapid sampling of arterial blood. Dogs were given graded doses of E . coli endotoxin ranging from 0.1 to 10 mg/kg. All injections were made directly into the femoral vein of the dog. Blood sam-9) 10).
D . C . 20012ples for histamine determination were then taken a t 0, 15,, 30, 45, and 60 sec and a t 2, 5, 10, 15, and 30 min after endotoxin. Plasma histamine determinations were made on platelet-free plasma. All samples were centrifuged a t > 5OOOg (gravities-centrifuged force)for 10 min and extracted in ethanol-chloroform (30/20) mixture. Following a single alkaline wash the samples were read on a fluorometer using the method of Shore (8).All animals were followed for 72 hr or until death.Rewlts. The effects of each of 22 injections of E. coli endotoxin on plasma histamine levels a t specific time intervals are shown in Table I. Doses ranged from 0.1 to 10.0 mgikg. Those doses of endotoxin which produced death within 72 hr are also indicated. I t is interesting to note that ultimate lethality is usually correlated with a sharp elevation of plasma histamine a t 30-60 sec postinjection.The response of the anesthetized dog to a sublethal (0.5 mg/kg) injection of endotoxin is such that a minimal increase in histamine, a subtle fall in platelets, and the slight decrease in blood pressure are evident (Fig. 1).In contrast, the response of the dog to a lethal (1.0 mg/kg) injection of endotoxin is such that a marked increase in plasma histamine is noted which occurs a t 30 sec and last...
