Several preparations of Cremophor E1, several of other non-ionic detergents and several components of Cremophor E1 were tested for their histamine-releasing capacity in dogs. Lutensol AP 10 and a derivative of 1,2-propylenglycol were ineffective, but showed excellent properties as detergents. Thus the histamine-releasing capacity was not necessarily combined with the tenside effect of the surfactants. Oleic acid found in Tween 80 as well as in Cremophor E1 seems to be the most effective constituent, but the alcohol seems also to be important for the histamine-releasing capacity. The development of a non-toxic solubilizer for lipophilic drugs seems of considerable clinical interest.

ing anaesthesia with both substances led us to undertake this investigation. To demonstrate, however, that the increased concentration of plasma histamine was actually free, pharmacologically active histamine, we studied gastric acid secretion, heart or pulse rate, and peripheral arterial pressure in the subjects of the investigation.

improved method for the determination of histamine release in man: its application in studies with propanidid and thiopentone, European J. Pharmacol. 19 (1972) 180-190. tlistamine 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 rain after thiopentone, the plasma histamine level was increased by 350 and 4205~ 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, ttalfmaximum 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 rain, 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 145 ng/kg)/min, which induced a half-maximmn gaslric 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, histamine release by propanidid and thiopentone is without significant clinical consequences, but it is important in anaphylactoid incidents occurring during anesthesia with these substances.

No abstract

Summary. Histamine concentrations in plasma, whole blood and various tissues of human subjects, monkeys, pigs and dogs were determined by fluorometric methods before, during and after surgical operations. Following intraabdominM surgery in 6 of 22 patients elevated plasma histamine levels were found several hours after the end of operation. Some of the causes of histamine release in surgery were found to be premeditation by atropine, intravenously administered anaesthetics, infusion of plasma substitutes and manipulation on the gut. Acute blood losses were without effect on the plasma histamine levels. Clinical symptoms and pathophysiological reactions, such as taehyeardia, hypotension, increased gastric secretion and anaphylactoid reactions could be related to the release of histamine in some circumstances.