Early Histamine Release and Death Due to Endotoxin

Abstract

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...

Evidence for the involvement of a plasma kallikrein‐kinin system in the immediate hypotension produced by endotoxin in anaesthetized rats

“…Because of the seriousness of the clinical symptoms associated with gram-negative septicaemia, several studies have been conducted to clarify the mechanisms responsible for the development of metabolic and haemodynamic abnormalities observed during endotoxin shock (Baue, 1968;Neuhof et al, 1970;Sardesai & Walt, 1971). Among the vasoactive substances released by endotoxin, such as histamine (Hinshaw et al, 1961;Vick et al, 1971), 5-hydroxytryptamine, catecholamines (Rosenberg et al, 1961) and kinins, bradykinin has been suspected of playing a major role in the widespread vascular disturbances seen during endotoxaemia. The involvement of the plasma kallikrein-kinin system in endotoxin shock has been 1 Author for correspondence.…”

THE POSSIBLE ROLES OF HISTAMINE, 5‐HYDROXYTRYPTAMINE AND PROSTAGLANDIN F2α AS MEDIATORS OF THE ACUTE PULMONARY EFFECTS OF ENDOTOXIN

“…The relevance of the release of so many highly 14 active substances to the pathophysiology of endotoxin shock is still not clear despite attempts (Vick, 1960;1965;Vick, Mehlman & Heiffer, 1971) to correlate early cardiovascular changes with the release of one or other of these agents. There are at least two possible approaches to the problem: (1) the detection of vasoactive agents in blood following endotoxin administration; (2) the classical pharmacological approach, of prevention of synthesis or release, and antagonism of effects of released vasoactive agents.…”

Binding between lipopolysaccharide and cecropin A

“…The high mortality rates has partly been attributed to lipopolysaccharide [ 1 ] in the outer membranes of GNB [2,3]. Administration of lipopolysaccharide (LPS) to experimental animals induce a clinical syndrome similar to that observed in humans with gram negative infections [4][5][6][7][8][9][10]. LPS has also been implicated in the pathogenesis ofbyssinosis [11][12][13][14].…”