Changes In Plasma Histamine Research Articles

Non-IgE-mediated hypersensitivity induced by multivitamins containing Tween-80.

Multivitamins have been widely used for years. Adverse reactions, especially hypersensitivity, to multivitamins are becoming noteworthy. However, the classification of hypersensitivity is confusing, and the trigger is unknown. Multivitamins consist of two vials labelled vial 1 containing Tween-80 and vial 2. Multivitamins without Tween-80 were used as a contrast. Behaviouristics, histamine, IgE, and blood pressure of beagle dogs and guinea-pigs were investigated by observation, ELISA and sphygmomanometer, and degranulation and apoptotic of RBL-2H3 cells were assayed by spectrophotometry and flow cytometry. The results showed that dogs suffered from multiorgan anaphylactoid symptoms, and dramatically decreased blood pressure, and high plasma concentrations of histamine after the first administration of multivitamins and multivitamins vial 1, which contains Tween-80, compared to the control, multivitamins vial 2 or multivitamins without Tween-80. In anaphylaxis assay, guinea-pigs did not display any anaphylaxis symptoms and there were no changes in plasma histamine and IgE concentrations in the multivitamins and multivitamins vial 1 groups or in the multivitamins vial 2 and multivitamins without Tween-80 groups except ovalbumin. Compared to the control, the release of β-hexosaminidase and histamine, and the apoptosis of non-antigen-sensitized RBL-2H3 cells significantly increased in the Tween-80 and multivitamins and multivitamins vial 1 groups in a concentration-dependent manner. However, there was no alteration in multivitamins vial 2 and multivitamins without Tween-80 groups. The results indicate that the hypersensitivity induced by multivitamins may be anaphylactoid reaction, but not anaphylaxis. Multivitamin-induced release of inflammatory factors is triggered by Tween-80 through a non-IgE-mediated pathway.

The Severe Adverse Reaction to Vitamin K1 Injection Is Anaphylactoid Reaction but Not Anaphylaxis

The severe adverse reaction to vitamin K1 injection is always remarkable and is thought to result from anaphylaxis. Paradoxically, however, some patients administered vitamin K1 injection for the first time have adverse reactions. Using beagle dogs, the present study tested the hypothesis that the response to vitamin K1 is an anaphylactoid reaction. The results showed that serious anaphylaxis-like symptoms appeared in beagle dogs after the administration of vitamin K1 injection for the first time. The plasma histamine concentration increased, and blood pressure decreased sharply. After sensitization, dogs were challenged with vitamin K1 injection and displayed the same degree of symptoms as prior to sensitization. However, when the vitamin K1 injection-sensitized dogs were challenged with a vitamin K1-fat emulsion without solubilizers such asTween-80, the abnormal reactions did not occur. Furthermore, there was no significant change in the plasma immunoglobulin E concentration after vitamin K1 challenge. Following treatment with vitamin K1 injection, the release of histamine and β-hexosaminidase by rat basophilic leukemia-2H3 cells as well as the rate of apoptosis increased. The Tween-80 group displayed results similar to those observed following vitamin K1 injection in vivo. However, the dogs in the vitamin K1-fat emulsion group did not display any abnormal behavior or significant change in plasma histamine. Additionally, degranulation and apoptosis did not occur in rat basophilic leukemia-2H3 cells. Our results indicate that the adverse reaction induced by vitamin K1 injection is an anaphylactoid reaction, not anaphylaxis. Vitamin K1 injection induces the release of inflammatory factors via a non-IgE-mediated immune pathway, for which the trigger may be the solubilizer.

Peripheral inflammatory activation after hippocampus irradiation in the rat

Purpose: To detect the possible biochemical signs of inflammatory activation in the peripheral circulation in a rodent model of hippocampus irradiation, and to examine the effects of L-alpha-glycerylphosphorylcholine (GPC) in this experimental protocol.Materials and methods: Anesthetized Sprague-Dawley rats were subjected to 40 Gy cobalt irradiation of both hemispheres of the hippocampus, with or without GPC treatment (50 mg/kg intravenously (i.v.), 5 min before the irradiation, n = 6, each). A third group (n = 6) served as saline-treated control. Blood samples were obtained 3 h after the end of irradiation in order to examine the changes in plasma histamine, tumor necrosis factor-alpha (TNF-α), interleukin 1-beta, interleukin 6 (IL-6) and interleukin 10 (IL-10); liver tissue samples were taken to determine adenosine triphosphate (ATP) concentrations.Results: The hepatic ATP levels were significantly declined, while plasma concentrations of circulating TNF-α, IL-6, IL-10 and histamine were significantly increased after hippocampus irradiation. GPC treatment significantly reduced the irradiation-induced release of cytokines and histamine, and the liver ATP level was maintained at the control value.Conclusions: Targeted brain irradiation produced measurable pro- and anti-inflammatory cytokine changes in the systemic circulation. GPC supplementation provides significant protection against irradiation-induced peripheral pro-inflammatory activation and ATP depletion.

Late-onset anaphylaxis to fermented soybeans: the first confirmation of food-induced, late-onset anaphylaxis by provocation test

Late-onset anaphylactic reactions without early-phase reactions are rarely reported. The hypothesized mechanism of late-onset anaphylaxis to fermented soybeans is delayed absorption or release into the bowel rather than an immunologic phenomenon. To investigate the mechanisms of late-onset anaphylaxis to fermented soybeans in 2 patients and to characterize the allergens involved in anaphylaxis caused by fermented soybeans. Two patients underwent skin prick-by-prick tests with fermented soybeans as is. We used an open challenge for the provocation test of anaphylaxis and measured changes in plasma histamine, plasma tryptase, serum eosinophil cationic protein, and plasma leukotriene B4 levels in 1 patient. In addition, specific IgE against fermented soybeans and the allergens of fermented soybeans were detected by enzyme-linked immunosorbent assay and immunoblotting, respectively. The results of the prick-by-prick tests with fermented soybeans as is were positive in both patients and negative in control subjects. The challenge with 50 g of fermented soybeans caused generalized urticaria and dyspnea 13 hours after ingestion of fermented soybeans in 1 patient. In addition, his plasma histamine and tryptase levels transiently elevated during the anaphylactic event. In enzyme-linked immunosorbent assay, the patients showed elevated IgE levels to the proteins of fermented soybeans. Serum IgE antibodies of patients 1 and 2 were bound to approximately 5- and 26-kDa proteins in immunoblotting of fermented soybeans, respectively. To our knowledge, this is the first report of late-onset anaphylaxis provoked by the challenge test half a day after ingestion of fermented soybeans.

Methylmethacrylate bone cement does not release histamine in patients undergoing prosthetic replacement of the femoral head

This study was designed to see if methylmethacrylate monomer bone cement released histamine in 13 patients undergoing total hip replacement surgery with a cemented prosthesis, compared with seven control patients receiving a cementless porous-coated prosthesis. Blood samples for plasma concentrations of histamine were obtained before the start of anaesthesia, immediately before insertion of methylmethacrylate bone cement into the shaft of the femur in the cemented fixation group or before insertion of the femoral component of the prosthesis in the cementless fixation group, and 15, 30 and 60 min after the start of implantation of the prosthesis. In both groups, changes in plasma histamine did not differ significantly from baseline before implantation of cement. There were no significant differences between groups. We conclude that methylmethacrylate bone cement does not release histamine during total hip replacement surgery.

The effect of inhaled allergen on circulating basophils in atopic asthma

There is increasing evidence for the role of basophils in the allergen-induced late asthmatic response (LAR). To study the effect of inhaled allergen on basophil function in subjects with asthma, ex vivo basophil spontaneous histamine release (SHR) in peripheral blood and plasma histamine was measured before and 2, 5, 10, and 15 minutes, and 2, 4, 6, and 8 hours after allergen bronchial challenge (allergen study day) in six subjects with atopic asthma. Allergen inhalation induced an early response and LAR consisting of a mean (± SD) 32.5% (± 7.9%) and 28.8% (±7.7%) fall in FEV 1, respectively. As a control for the effects of bronchoconstriction, on another occasion, methacholine challenge was performed to produce a mean 33.4% (±3.4%) fall in FEV 1 during the early response and no LAR, and blood was obtained to measure basophil histamine release (HR) and plasma histamine. There was a small, but significant ( p < 0.05), rise in median SHR from 4.6% to 6.1% of total basophil histamine after allergen but not after methacholine inhalation. HR remained high after allergen inhalation during the 8 hours of study, whereas it demonstrated a steady, significant, decrease between 4 to 8 hours after methacholine inhalation. No significant changes in plasma histamine were recorded on either allergen or methacholine study days. On a third occasion, SHR was measured after challenge with physiologic saline to control for any effects of methacholine on SHR, and a decrease in HR was recorded during the day similar to HR observed after methacholine challenge. These studies suggest an enhancing effect of inhaled allergen on SHR The increase in SHR ev vivo is not necessarily associated with increased plasma histamine levels in vivo and may be more a reflection of basophil activation, possibly involving histamine-releasing factors and cytokines.

Histamine release in the course of elective conventional cholecystectomy in aged patients: Problems in defining release in relation to specific intraoperative events

The effectiveness of an H1 −+H2-prophylaxis against perioperative acute pseudoallergic reactions in which histamine is involved, and against postoperative complications the incidence of which may be increased by these reactions, was the central problem of a randomized trial in 162 aged patients during elective conventional cholecystectomy. As main endpoint it was planned to use the systemic histamine release reaction, as it already had been defined for the conscious and anaesthetized human subject. However, it had to be reassessed and redefined for the intraoperative period after improvement of the plasma histamine assay and new findings about stress-induced histamine release and the kinetics of histamine release during certain phases of operation. Intraoperative release is, at present, defined solely as an increase of plasma histamine values after a particular action (phase of operation). It includes criteria concerning plasma histamine changes either in comparison to the base value before surgery or to the preceding value before the last surgical action. Histamine elevations must exceed the last value by more than 3 standard deviations of the analytical error (i.e. 200% if value <0.25 ng/ml and 40% above). Basic requirements for the histamine assay (quality control), correct sample taking and appropriate preparation have to be fulfilled over the whole trial period. When these criteria were applied to the 162 patients an overall incidence of histamine release during cholecystectomy of 55.6% was found with 9.7–20% during an individual phase of operation. The data of this study, performed under routine conditions, with a sufficient number of patients with elevated risk and event controlled plasma histamine values, lead to a better understanding of intraoperative histamine release, its incidence and extent.

CHANGES IN PLASMA HISTAMINE AND TRYPTASE CONCENTRATIONS FOLLOWING FOOD CHALLENGES IN CHILDREN WITH FOOD ALLERGY

This study was undertaken to determine whether the measurement of plasma histamine and tryptase concentrations after food challenges provides an additional predictive marker for the diagnosis of food allergy. In 13 patients who were sensitive to food antigen-specific IgE, 21 oral food challenges were performed. In 5 non-atopic subjects (controls), 5 oral food challenges were performed in the same manner.Plasma histamine concentration was measured by RIA before and 5, 15, 30, 60, 120, 240, min after challenge. Plasma tryptase concentration was measured by RIA before and 60, 120, 240min after challenge.Significant rise in plasma histamine concentrations was observed at 120 and 240min after challenge in patients who had some hypersensitivity reactions. Plasma tryptase levels were significantly increased at 240min after challenge in the same patients.No significant change in plasma histamine and tryptase concentrations was observed after the challenges in the controls.The results suggest the possible relationship between provocation symptoms with food challenge and elevation of plasma histamine and tryptase levels.Plasma histamine and tryptase measurement of concentrations after food challenge may be useful in diagnosis of food allergy.

Histamine release from the administration of suxamethonium and atracurium in adolescents

Cutaneous reactions and plasma histamine levels were evaluated in 30 adolescents subsequent to the administration of suxamethonium 1.5 mg kg−1 or atracurium 0.6 mg kg−1. Plasma histamine levels were measured by the radio-enzymatic assay using histamine N-methyl transferase. In the atracurium group, the change in plasma histamine level was significant at the 2 min mark, but was not significant in the suxamethonium group. About 60% of the patients in each group developed a cutaneous reaction. Erythematous cutaneous reactions following atracurium were frequently associated with a mild increase in plasma histamine levels, whereas the rashes induced by suxamethonium in adolescents were not associated with changes in plasma histamine.

The relationship between plasma histamine concentrations and bronchial obstruction to antigen challenge in allergic rhinitis

Antigen activation of pulmonary mast cells causes mediator release and airway obstruction in allergic patients with asthma. Concomitant measurements of airway mediators and pulmonary function are technically difficult, even with bronchoalveolar lavage. Thus, a procedure was developed to evaluate further the relationship between mediator release, as measured by plasma histamine concentrations, and airway obstruction in patients with allergic rhinitis challenged with inhaled ragweed antigen. At an initial challenge, the cumulative antigen dose to decrease the FEV 1 by approximately 20% was determined. Approximately 4 weeks later, the entire predetermined cumulative antigen dose to decrease the FEV 1 by approximately 20% was administered in five consecutive inhalations with simultaneous monitoring of plasma histamine. We found the percent fall in FEV 1 (24.3 ± 2.3 versus 30.4 ± 4.0; p > 0.05; n = 7) was similar whether antigen was administered by a cumulative or single-dose challenge. With the single-dose antigen challenge and monitoring blood samples frequently, we found plasma histamine (picograms per milliliter) values to increase from 73 ± 17 to 1071 ± 377 ( p = 0.022) with peak values 5 minutes after challenge. Furthermore, we found that the intensity of airway obstruction to antigen corresponded to both the patient's baseline airway responsiveness to histamine and the absolute changes in plasma histamine after antigen challenge. Thus, the degree of airway obstruction to inhaled antigen is determined by both the intensity of the allergic reaction (as reflected by the plasma histamine value) and bronchial responsiveness.

Neurogenic inflammation, vascular permeability, and mast cells.

Electrical stimulation (ES) of sensory nerves causes increased vascular permeability and vasodilatation, a process known as neurogenic inflammation. The purpose of this study was to assess the role of mast cells in neurogenic inflammation induced by ES of sensory nerves. ES of the rat saphenous nerve for 1, 3, 5, 15, or 30 min induced a 166 to 436% increase in the amount of 125I-albumin deposited in the skin. Through the initial 15 min of ES, the histamine content of the skin remained unchanged. However, 30 min of ES caused a 22.1% decrease in skin histamine (p less than 0.05). ES for 5 min followed by measurement of vascular permeability from 0 to 30 min thereafter resulted in maximal increases in 125I-albumin in the skin immediately after cessation of the pulse of ES. When skin histamine was measured at various intervals after a 5-min pulse of ES, no change in the histamine content was observed through the subsequent 30 min. When mast cell degranulation was assessed histologically, 5 min of ES failed to stimulate mast cell degranulation. However, 30 min of ES caused a significant increase in the proportion of degranulating mast cells. When draining venous plasma histamine was monitored before, during and after ES, no change in plasma histamine was observed. In contrast, the intradermal injection of 5 micrograms of compound 48/80 produced a significant increase in plasma histamine. In order to examine the possibility that histamine might be released but remain in the skin after ES, skin "blisters" were developed by intradermal injections of saline. There was a significant increase in the amount of 125I-albumin extravasated into blister fluid measured after 3, 5, and 10 min of ES and a significant increase in histamine after 5 or 10 min. Therefore, prolonged ES of sensory nerves can cause mast cell degranulation. However, ES causes increased vascular permeability at times when no mast cell activation can be observed. These data suggest that the initial phases of neurogenic inflammation are independent of mast cell activation.

Changes in plasma histamine during orthotopic liver transplantation in the pig

Hypotension and cardiac arrhythmia are commonly seen during liver transplantation both in man and in experimental animals. The cardiovascular changes may be explained by release of vasoactive substances, e.g. histamine, into the systemic circulation. Abdominal operations are followed by an increased histamine concentration in portal blood. If the liver clears excess histamine from the splanchnic system, an increased histamine concentration should not be found in the systemic circulation. We measured plasma histamine in peripheral arterial blood, blood from the right atrium and portal blood in different phase of liver transplantation in ten pigs. Histamine concentration increased in the portal vein in the anhepatic phase (basal 15.85 pmol/ml to 34.67 pmol/ml, median, p less than 0.05) but no changes were found in arterial or right atrium samples. Venous and later arterial revascularisation were not followed by any changes in histamine concentration in arteria and right atrium samples. We conclude that the transplanted liver can eliminate splanchnic histamine and that histamine is unlikely to be involved in the cardiovascular changes which are seen after revascularisation of the liver.

Adverse reactions during intravenous urography: are these due to histamine release?

The effects of four different radiographic contrast media (Urovison 58%, Hexabrix 320, Iopamiro 370 and Omnipaque 300) have been examined with respect to histamine release, cardiovascular changes and adverse drug reaction (ADR) in a group of 200 patients undergoing intravenous urography. Each patient received only one of the four agents, which were allocated on a random basis. Urovison produced the greatest number of ADRs. Iopamiro caused the least. No significant correlation between the magnitude of the change in plasma histamine following injection of radiographic contrast medium and the production of a particular ADR could be demonstrated. Heart rate increased significantly following the administration of Urovison, Hexabrix and Iopamiro in the absence of any appreciable change in blood pressure. These results and our earlier findings would favour the use of the low-osmolality contrast media in intravenous urography to minimize ADRs, histamine release and patient discomfort.

Plasma histamine and catecholamines during carbachol-induced bronchoconstriction in normal subjects

To determine (1) whether changes in plasma histamine occurred during provoked bronchospasm and (2) if so, whether such changes could be related to variations in plasma catecholamines, venous plasma histamine and catecholamines were measured during a dose-response carbachol challenge in eight healthy volunteers. A significant rise in plasma histamine was observed, whereas induced bronchoconstriction was small, 80% ± 4 % of initial specific airway conductance. There was no further increase in plasma histamine, whereas induced bronchoconstriction became more marked (70%, 60%, and 50% of specific airway conductance initial value). Plasma catecholamines did not change throughout the study. We conclude that mast cell degranulation occurs during a carbachol challenge, and that the variations in plasma histamine are not related to changes in plasma catecholamines.

Immunologic studies in allergen-induced late-phase asthmatic reactions

We have measured plasma histamine, serum neutrophil chemotactic activity (NCA) and complement (C3 and C4) over a 24-hour period in patients experiencing either early- and late-phase (dual) or single early asthmatic reactions to inhaled allergens. There was a significant biphasic elevation in plasma histamine, which paralleled the fall in forced expiratory volume in 1 sec in 10 patients with dual responses, whereas in seven subjects with single early reactions, only a single early increase in histamine concentrations was observed. In general, in the individual subjects, the changes in plasma histamine paralleled both the elevations in serum NCA and the decreases in forced expiratory volume in 1 sec. By gel filtration on Sephacryl S-400, anion exchange chromatography on DEAE Sephacel, and chromatofocusing with Polybuffer Exchanger 94, the major NCA of both the early and the late reactions was associated with proteins having an estimated molecular size of 600,000 daltons, an elution from DEAE Sephacel at 0.15M to 0.30M of NaCl (pH 8.1), and a pI of approximately 6.5. There were no appreciable changes in serum C3 and C4 up to 24 hr after challenge in subjects with late-hase responses. The patterns of asthmatic response were not related to either the total or allergen-specific serum IgE or IgG 4 concentrations. These results support the view that mediators of hypersensitivity participate in late-phase as well as early asthmatic reactions.

Exercise and isocapnic hyperventilation-induced bronchoconstriction in asthma: Relevance of circulating basophils to measurements of plasma histamine

The relationship of airway cooling during exercise to changes in airway caliber, plasma histamine levels, and circulating basophils was investigated in eight allergic asthmatic and eight normal subjects. In asthma matched RHE during exercise and ICH produced almost identical bronchoconstriction with maximum falls in sGaw of 61.0 ± 4.5% and 57.9 ± 5.2%, respectively. A similar RHE in normal subjects was associated with a 7.9 ± 3.3% fall in sGaw. The resting plasma-histamine levels were higher in the asthmatic (0.52 ± 0.06 ng/ml) than in the normal (0.31 ± 0.07 ng/ml, p < 0.05) subjects. No significant change in plasma histamine occurred after exercise in either group nor in the asthmatic subjects with ICH. In contrast, exercise but not ICH stimulated an increase in leukocytes, basophils, and total blood histamine in parallel with the airway response that reached a maximum at 2 to 5 min in both normal and asthmatic subjects. There was a positive correlation between basal plasma and total blood-histamine levels (r = 0.67, p < 0.01) in normal and asthmatic subjects suggesting that basophils contribute significantly to plasma histamine. The spontaneous basophil release of histamine was greater in asthmatic (13.4 ± 2%) than in normal subjects (6.46 ± 7%, p < 0.005), which is consistent with the higher resting plasma-histamine levels in the asthmatic subjects. These findings suggest that plasma-histamine changes with exercise in asthma but not ICH may be related to the associated basophilia and sample handling rather than intrapulmonary mast cell degranulation.

Histamine Release During Morphine and Fentanyl Anesthesia

High doses of morphine produced peripheral vasodilation and frequently significant hypotension. These effects are thought to be due, in part, to the release of histamine. One putative advantage of high-dose fentanyl anesthesia is its relatively small effect on peripheral vascular resistance. In a randomized study, the authors examined the possibility that the hemodynamic differences between morphine and fentanyl might be attributable to histamine release. Fifteen patients were studied prior to coronary artery bypass surgery. Subjects received in infusion of morphine (1 mg . kg-1, iv at 100 micrograms . kg-1 . min-1 [n = 8]) or fentanyl (50 micrograms . kg-1 at 5 micrograms . kg-1 . min-1 [n = 7]). Patients in the morphine group had an average 750 per cent peak increase in plasma histamine accompanied by a significant decrease in mean arterial pressure (-27 mmHg- and systemic vascular resistance (-520 dyne . s . cm-5). The greatest decrease in systemic vascular resistance occurred in those patients with the highest levels of plasma histamine (r = -0.81). Patients in the fentanyl group had no change in plasma histamine and no decrease in arterial pressure or systemic vascular resistance. Cardiac output and heart rate were comparable between the two groups. Differences in the release of histamine account for most, if not all, of the different effects of morphine and fentanyl on the peripheral vasculature.

Histamine, neutrophil chemotactic factor and circulating basophil levels following exercise in asthmatic and control subjects.

Significant increase in the maximum post-exercise values of plasma histamine (PH), whole blood histamine (WBH) and neutrophil chemotactic factor (NCF) occurred in arterial blood within the first hour after exercise in asthmatic patients. However, similar changes in PH and WBH also occurred in the control group. Significant increases in circulating basophil counts following exercise were found in both groups, which closely mirrored the changes in PH and NCF, and there was a highly significant correlation between rises in WBH and basophil counts (P less than 0.001). When plasma histamine as assayed in venous blood using a more sensitive and specific double isotope radio enzymatic assay no significant alteration in plasma histamine levels was detected in either the asthmatic or the control group. We conclude that there is no evidence from these studies to support the suggestion that mast cell mediator release is involved in the pathogenesis of exercise-induced asthma, and that any observed changes in levels of PH and NCF after exercise may be related to changes in levels of circulating basophils.

Venous plasma histamine in exercise- and hyperventilation-induced asthma in man.

1. Venous plasma histamine was measured by a specific and sensitive radioenzymatic assay in seven male extrinsic asthmatic and six age-matched non-atopic non-asthmatic male subjects during exercise and voluntary isocapnic hyperventilation. 2. There was no change in peak expiratory flow in normal subjects with exercise or hyperventilation, but asthmatic subjects showed a 29.4 +/- SEM 5.8% fall after exercise and a 29.0 +/- 5.4% fall after matched hyperventilation. 3. Plasma histamine was significantly higher (P less than 0.05) in asthmatic (6.2 +/- 0.95 nmol/l) than that in normal subjects (3.4 +/- 0.61 mol/l) and showed a significant (P less than 0.01) rise (to 14.4 +/- 1.83 nmol/l) during exercise in asthmatic, but not in normal subjects. This suggests that discharge of mast-cell mediators may occur during exercise in asthmatic subjects who develop exercise-induced asthma. 4. With hyperventilation there was no change in plasma histamine in either asthmatic or normal subjects, but this does not exclude the possibility that mediators may be released locally in the airways.

Role of histamine in the hypotensive action of d-tubocurarine in humans.

The administration of d-tubocurarine (dTc) to animals and humans has been reported to produce hypotension. Experiments in animals suggest that the hypotension is a result of both ganglionic blockade and histamine release. In order to determine the role of histamine release in dTc-induced hypotension in humans, the authors developed a sensitive radioenzymatic assay for plasma histamine and measured plasma histamine following dTc administration (0.25-0.75 mg/kg) to 21 surgical patients. While neither fentanyl (3 microgram/kg) nor thiopental (6 mg/kg) produced a significant change in plasma histamine, dTc caused a dose-dependent increase in plasma [dose dTc vs. log (plasma histamine), r = 0.62 P less than 0.003]. The log (plasma histamine) correlated with the dTc-induced hypotension (r= 0.61, P less than 0.005). The data suggest that histamine release is an important factor in the hypotension accompanying dTc administration in humans.