Histamine Release and Endotoxin Shock in the Primate*

Hinshaw, Lerner B.; Jordan, Margaret M.; Vick, James A.

doi:10.1172/jci104385

Cited by 57 publications

(25 citation statements)

References 36 publications

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“…The sources of infections were the skin and soft tissue (13), abdomen (13), lung (seven), urogenital tract (three), and other sites (four). Blood cultures were positive in 36 patients, 21 with gram-negative bacteria, 12 with gram-positive bacteria, and three with multiple bacteria. In the four patients with negative blood cultures that were attributed to concomitant broad-spectrum antibiotic treatment, the infectious agent was isolated from purulent exudates.…”

Section: Resultsmentioning

confidence: 99%

Coronary hemodynamics and myocardial metabolism of lactate, free fatty acids, glucose, and ketones in patients with septic shock.

Dhainaut¹,

Huyghebaert²,

Monsallier³

et al. 1987

Circulation

340

122

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To investigate disturbances in the coronary circulation and myocardial metabolism during septic shock, we examined coronary sinus blood flow and myocardial substrate extraction in 40 patients with septic shock and 13 control patients. Patients with coronary artery disease were excluded from this study. The global hemodynamic pattern of the septic patients was characterized by a lower stroke volume, despite an elevated cardiac index. Coronary sinus blood flow was high (187 + 47 vs 130 ± 21 ml/min in the control group, p < .001) due to marked coronary vasodilation, especially in the subgroup of nonsurvivors. In contrast to the control group, myocardial lactate uptake was elevated, while that of free fatty acids, glucose, and ketone bodies was diminished in patients with septic shock. These findings were especially prominent in the nonsurvivors. Expressed as oxygen equivalents, the contribution of free fatty acids as an energy source of the myocardium was markedly diminished in septic patients (12% vs 54% in the control group, p < .005), while that of lactate was increased (36% vs 12%, p < .01). The observed shift in myocardial substrate extraction was associated with a discrepancy between measured myocardial oxygen consumption and that calculated chemically from commonly available exogenous substrates: 41 % of myocardial oxygen consumption was not explained by the utilization of commonly available substrates extracted from coronary circulation in all patients with septic shock. These data indicate that myocardial utilization of endogenous substrates may probably account for this discrepancy, suggesting that a "mandatory" utilization of endogenous energy sources might underlie progressive cardiac involvement in septic shock. Circulation 75, No. 3, 533-541, 1987. SEPTIC SHOCK is a frequent and serious disorder with a high mortality. In recent years, increasing attention has been directed to the study of the hemodynamic and metabolic alterations accompanying septic shock.

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Section: Resultsmentioning

confidence: 99%

Coronary hemodynamics and myocardial metabolism of lactate, free fatty acids, glucose, and ketones in patients with septic shock.

Dhainaut¹,

Huyghebaert²,

Monsallier³

et al. 1987

Circulation

340

122

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“…This has been primarily because plasma levels of histamine increase gradually after the administration of lethal amounts of endotoxin (10,32) and because endotoxin enhances histidine decarboxylase activity (3). The findings that compound 48/80, a potent histamine-releasing com-pound, and histamine both induce vascular changes similar to those induced by endotoxin has prompted investigators to assign a primary role to histamine as the triggering device of endotoxin shock (4).…”

Section: D) Sensitivity Experimentsmentioning

confidence: 99%

Vasoactive Mediators as the “Trigger Mechanism” of Endotoxin Shock*

Jacobson¹,

Mehlman²,

Kalas³

1964

J. Clin. Invest.

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The mechanisms by which endotoxin induces a profound shock state have not been clearly established. Several neurohumoral agents have been implicated as mediators of endotoxin shock. These include histamine (1-4), catecholamines (5-7), and serotonin (7-9).Inferences of the role played by any of these mediators have been derived from four types of evidence: a) the hemodynamic alterations observed in endotoxemia are simulated by vascular effects of the naturally occurring substance (4, 5), b) plasma concentrations of the neurohumoral agent undergo changes in endotoxin shock (7, 10-13), c) vascular reactivity to the agent is altered in endotoxemia (5,6,14), and d) pharmacological antagonists to the substance in question prevent certain responses to endotoxin (4,(15)(16)(17).That a primary role could be assigned to any single substance in endotoxin shock is doubtful, however, because of the complexity of endotoxemia and the frequently conflicting and occasionally inconclusive nature of the evidence (18). Our investigation was prompted by the uncertainties concerning the relative importance of several proposed intermediaries in the early phase of endotoxin shock. Experiments were designed to utilize some of the approaches mentioned above. MethodsStudies of endotoxin shock were performed in 71 dogs of both sexes weighing 10 to 20 kg each. All animals were anesthetized with pentobarbital sodium (30 mg per kg). These experiments may be divided into three types: a) those in which endotoxemia was induced in animals pretreated to deplete tissue supplies of histamine, catecholamines, or serotonin; b) studies in which the hemo-* Submitted for publication October 21, 1963; accepted January 23, 1964. Presented in part at the Midwestern Section Meeting of the American Federation for Clinical Research, Chicago, Ill., October 31, 1963. dynamic and chemical effects of infused histamine, catecholamines, acetylcholine, or serotonin were compared with the effects of endotoxin injection; and c) experiments in which vascular sensitivity to histamine, catecholamines, or serotonin was determined at various times before and after injecting endotoxin. The design of these experiments is outlined in Table I.Mean pressures in millimeters of Hc were monitored in arteries, veins, or perfusion circuits by pressure transducers and recorded on an oscillograph.1 Plasma concentrations of epinephrine and norepinephrine (micrograms per liter) were determined by the method of Weil-Malherbe and Bone (19) as modified in this laboratory (20). Platelet-free plasma concentrations of serotonin were determined by the method of Waalkes (21) using an interim wash with salt-saturated NaOH to remove residual traces of histidine. After the final acid extraction one sample was employed for the assay of serotonin; another sample was used for the fluorometric determination of histamine (22) Experiments and Results a) Control experimentsHeparin sodium (10 mg per kg) was administered to all dogs used for control (groups C and PV) and depletion (groups F and R) ex...

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“…If an immune mechanism were involved, histamine could be one of the substances that was liberated by an antigenantibody mechanism, and studies do point to histamine as a factor causing the altered vascular activity (3,(8)(9)(10). This report concerns the study of complement titers, plasma histamine concentrations, and blood pressure changes in a series of dogs given a lethal * Submitted for publication August 15, 1963; accepted December 12, 1963. Supported by U. S. Public Health Service grant dose of endotoxin.…”

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confidence: 99%