Changes In Plasma Histamine Research Articles

Inhalation challenge and pharmacologic studies of toluene diisocyanate (TDI)—sensitive workers

Workers with “sensitivity” to toluene diisocyanate (TDI) studied in depth in an attempt to determine mechanisms of bronchial hyperreactivity. Tests included provocative inhalation challenge (PIC) with TDI and methacholine challenge. Blood samples obtained prior to and at various times after PIC were used to measure complement and split products of complement and plasma histamine levels and to determine dose-response slopes of lymphocyte cyclic adenosine monophosphate (cAMP) following stimulation with agonists. TDI-reactive individuals were all reactive to methacholine and responded to PIC with TDI by immediate, delayed, or dual bronchospastic reactions. No change in plasma histamine, total complement levels, or split products of complement were measurable. TDI reactors gave decreased lymphocyte cAMP dose response slopes to stimulation with isoproterenol, prostaglandin E 1, and TDI, which suggests that impairment of adrenergic receptors may play an important role in TDI reactivity.

Plasma histamine changes during provoked bronchospasm in asthmatic patients

Seven patients with bronchial asthma underwent bronchial inhalation challenge with aerosolized allergen extracts and methacholine. Simultaneously, venous blood samples were collected and histamine was measured. Each patient was challenged on successive days with an allergen extract to which he had no skin-sensitizing antibody (skin test-negative allergen), followed by methacholine and skin test-positive allergen. Bronchospasm was not induced by inhalation of skin test-negative allergens but was observed in all patients after methacholine and in the majority of patients after skin test-positive allergens. No changes in plasma histamine were detected after challenges with methacholine and skin test-negative allergens. After challenge with skin test-positive allergens, significant rises in plasma histamine were detected in 5 of 7 patients. Plasma histamine was elevated within the first 5 min after inhalation of aerosolized allergen, and elevations persisted as long as 30 min. These studies showing that histamine increases significantly in the plasma during allergen-induced asthma in man suggest that histamine should be considered as at least one of the mediators of bronchospasm in allergic asthma. Bronchospasm induced by the cholinergic drug methacholine, unlike allergen-induced bronchospasm, is not associated with changes in plasma histamine.

An improved method for the determination of histamine release in man: Its application in studies with propanidid and thiopentone

Histamine release by propanidid and thiopentone was demonstrated with the use of a highly sensitive and specific method for determining histamine in human plasma. 5 min after i.v. administration of propanidid and 3 min after thiopentone, the plasma histamine level was increased by 350 and 420% respectively. In whole blood, histamine release could be demonstrated only when the basophil content remained constant. This was the case in about 50% of test persons after injection of propanidid, but not after administration of thiopentone where the basophil content decreased in all probands by about 35%. The increase of the histamine concentration in plasma was 3 ng/ml and in whole blood, 24 ng/ml. Half-maximum gastric acid secretion was elicited by injection of propanidid and thiopentone. It was increased by very rapid application of propanidid and diminished by premedication with atropine by about 30%. The changes in plasma histamine and gastric secretion were parallel over 30 min, whereas tachycardia and peripheral arterial hypotension lasted for only 3–4 min. During i.v. infusion of histamine a correlation could be shown between the doses infused, (15–90 ng/kg)/min, and the elevation of the plasma histamine concentration. 3 ng/ml plasma were measured at a dose of (45 ng/kg)/min, which induced a half-maximum gastric secretion, but was without effect on blood pressure and heart rate. It is concluded that only the increase of plasma histamine concentration, not that of whole blood, represented the release of free, pharmacologically active histamine. In normal test persons, hisramine release by propanidid and thiopentone is without significant clinical consequences, but it is important in anaphylactoid incidents occurring during anesthesia with these substances.