Plasma histamine

Histamine in the Blood. After its release, histamine diffuses rapidly into the blood stream and surrounding tissues (12). Histamine appears in blood within 2.5 min after its release, peaks at 5 min, and returns to baseline levels by 15 to 30 min. In humans, the diurnal mean of plasma histamine levels is 0.13 ng/g. In urine, elevations of histamine or metaboUtes are more prolonged than plasma elevations. Consequendy, abnormahties are more easily detected by urinary histamine assay. About one-half of the histamine in normal blood is in basophils, one-third in eosinophils, and one-seventh in neutrophils the remainder is distributed among all the other blood components. Increases in blood histamine levels occur in several pathological... 

Histamine is a critical mediator in anaphylactic reactions. It is a diamine produced by decarboxylation of the amino acid histidine in the Golgi apparatus of mast cells and basophils. Once secreted, it is rapidly metabolized by histamine methyltransferase [2]. Plasma histamine levels are elevated in anaphylaxis, reaching a concentration peak at 5 min and declining to baseline by 30-60 min [3]. Therefore, histamine samples for assessing an anaphylactic reaction should be obtained within 15 min of the onset of the reaction. Urinary metabolites of histamine may be found for up to 24 h. 

As immediately after the reaction, elevated plasma histamine and serum or plasma tryptase levels of histamine and tryptase have been found [31, 34], an anaphylaxis may be confirmed by blood samples for histamine analysis drawn as soon as possible after the reaction and for tryptase drawn 1-2 h after onset of symptoms [31]. Tryptase values have to be compared to baseline levels. 

Fig. 2. Increasing plasma histamine concentration in a patient undergoing dental treatment without further medication [from Ring, 1986].

Figure 4.4. Plasma histamine levels in response to NT given at t = 0. Rats were anaesthetized and NT (5 nmol/kg) or saline (0-3 ml) given intravenously. Blood was collected at the indicated times. Mean S.E.M. of mean of n values (in parentheses). Horizontal arrow is the histamine level before NT.

SP produces a pronounced (4-fold) increase in the histamine content of the venus outflow of the perfused rat hindquarters [91] and, when injected intravenously in intact animals, it produces a significant increase in the level of plasma histamine and in the hematocrit and a pronounced fall in systemic blood pressure [102], In these experiments, pretreatment with the steroid, dexamethasone, reduced the SP-induced elevations in plasma histamine and hematocrit neurotensin and compound 48/80 were found to be similarly... 

When given rapidly, protamine causes hypotension due to a decrease in vascular resistance, possibly linked to the release of nitric oxide from endothelium. Flypotension can be minimised by slow administration over 10-15 minutes. Protamine does not affect myocardial contractility. In some patients, systemic hypotension occurs in conjunction with pulmonary hypertension and, in severe cases, right ventricular failure. The mechanism is activation of the complement pathways by the heparin-protamine complex leading to release of thromboxane A2, which mediates pulmonary vasoconstriction. Unlike in anaphylaxis, plasma histamine concentrations are not increased. When this syndrome develops protamine administration should be stopped, and some have recommended giving heparin in an attempt to reduce the size of the heparin-protamine complex. 

Peptides that present allergen-specific T-cell epitopes retain the ability to immuno-modulate T-cells, but less an ability to cross-link IgE and activate effectors cells. For example, synthetic peptides-based vaccine derived from major peanut allergen, Ara h 2 composed of thirty 20-mers that overlapped by 15 amino acids (Sicherer and Sampson 2007). Subcutaneous or intranasal administration of the vaccine reduced Ara h 2-specific IgE and plasma histamine release levels as well as anaphylactic symptoms scores in a murine model of peanut anaphylaxis. 

Some investigators suggested that implantation of acrylic bone cement into the femur increases plasma histamine, which, especially in elderly patients with pre-existing cardiac diseases and/or hypovolemia, can cause serious, sometimes fatal, cardiovascular complications (9). 

Rapid infusion of cimetidine causes an increase in plasma histamine concentration, and this could be one reason for its cardiac effects. A marked degree of bradycardia (for example a 30% reduction in heart rate) is uncommon although well recognized (SEDA-17, 417) sinoatrial and atrioventricular conduction effects and dysrhythmias of every possible type have occasionally been noted, particularly after infusion but also with oral therapy. It has been suggested that if a patient is particularly at risk (for example because of poor renal function) the electrocardiogram should be monitored (SEDA-15, 394). 

Clinical problems due to histamine release after bolus administration of cisatracurium have not been observed, even with very large doses up to 0.4 mg/kg (3,8), but in some patients there were considerable increases in plasma histamine concentrations (8-10). 

No rise in plasma histamine concentration was found with bolus doses up to 0.08 mg/kg (1), but in one case there was transient hypotension 1 minute after a bolus dose of 0.05 mg/kg via a pulmonary artery cannula, with cutaneous flushing at 2 minutes, suggesting that histamine release can occur on occasion (3). There was no tachycardia or bronchospasm, but the mean arterial pressure fell from 88 to 40mmHg and recovered with therapy within 3 minutes, by which time the skin flushing was fading. 

In a study of 54 patients, plasma histamine concentrations increased by 200% following doxacurium in two patients, but there were no changes in heart rate or blood pressure (4). Indeed, cardiovascular stability has been reported in several studies (1,4) and only minor clinically insignificant changes have been seen with doses up to 0.08 mg/kg, even in cardiac patients (AHA classes III-IV) (5,6). 

The effect of formoterol 18 micrograms on histamine-induced plasma exudation into sputum has been investigated in 16 healthy subjects in a double-blind, placebo-controlled, crossover study. Plasma exudation into the airways was produced by inhalation of histamine. Sputum was induced by inhalation of hypertonic (4.5%) saline. Induced sputum was obtained at baseline and then at 30 minutes and 8 hours after histamine inhalation. Sputum concentrations of alpha2-macroglobulin were measured as a marker of microvascular-epithelial exudation of bulk plasma. Histamine-induced plasma exudation 30 minutes after placebo was considerably greater than at baseline. The median difference was 11 pg/ml (95% Cl = 0.9, 90) expressed as alpha2-macroglobulin. The... 

A major adverse effect of rapacuronium is an increase in heart rate (3). Plasma histamine concentrations may increase after rapacuronium injection, but this was not correlated with changes in blood pressure or heart rate (4). 

Rocuronium is a steroidal agent related chemically to vecuronium. It is less potent than vecuronium and has a quicker onset of action. The plasma clearance of rocuronium is primarily due to liver uptake and bihary excretion (1). About one-third of an injected dose is excreted unchanged in the urine (1). Good intubating conditions may be expected 90-120 seconds after the injection of 0.6 mg/kg rocuronium. Increasing the dose to 1 mg/kg will give acceptable intubating conditions at 60 seconds. There were no increases in plasma histamine concentrations with doses up to 1.2 mg/kg (2). 

In humans the allergic reactions from contrast media resemble those elicited by histamine injection, and the unpleasant side effects are rarer after fast injection than after slow injection of the same dose of contrast medium (489). Seidel et al. (724) showed that usual doses of chemically different contrast media were able to affect the plasma histamine levels in venous blood of healthy persons. Histamine release ceases when the dose rate is reduced to 0.17 g kg min This may explain the advantage of administering urographic agents by infusion to avoid reactions. 

Lodoxamide (0.1 mg via aerosol) protected against grass pollen antigen in asthmatics. The chromone derivative (28) (FPL 58668) given via aerosol inhibited Ascarls-lnduced bronchoconstriction and the concomitant increase in plasma histamine levels in laboratory-bred monkeys. The pyrimidine (29) (BL 5255) inhibited mediator release... 

The median normal histamine concentration in the 30 control plasmas was 5. 0(4. 8 - 6. 1) ng/ml (confidence limits according to Owen, 44). Four hours after oral administration of oxatomide the median of the treated groups stayed within the control limits, except for the group treated with 10 mg g, in which the median plasma histamine concentration was 3. 0 ng/ml. 

The lowest dose of oxatomide, 0. 63 mg g, had no effect on the histamine levels, but from the dose of 1.25 mg/kg and above significantly less histamine was found in comparison with the corresponding control data. Half an hour after Cremophor injection the plasma histamine concentration was virtually normal in dogs treated with 2. 50 mg g or more of oxatomide. A reduction to half of the control histamine levels was obtained with the dose of 2. 7 5 mg g at the 5 min-interval 15 and 30 min after Cremophor injection the same reduction was obtained with doses of 1. 90 and 0.88 mg g respectively. 

Histamine Clearance in Dogs. It has previously been reported that mepyramlne incr ses fhe rate of histamine elimination from the circulation of guinea-pigs (45). It is conceivable that a similar effect played a role in the reduction of plasma histamine by oxatomide in the Cremophor experiments, especially since the reduction was more pronounced with time. An additional experiment was arranged to determine whether oxatomide changes the rate of histamine elimination. 

Brashear RE, Kelly MT, White AC (1974) Elevated plasma histamine after heroin and morphine. J Lab Clin Med 83 451... 

Various procedures were used to answer these questions, including direct skin tests, Prausnitz-Kiistner reaction, intravenous test doses and in particular the measurement of histamine release from leucocytes in vitro. We found the latter test extremely useful (Assem 1977 a). Lorenz and Doenicke (1978) measured plasma histamine levels in vivo, and other authors found complement studies of great value (Watkins et al. 1978) Watkins 1979 Dye and Watkins 1980). 

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