Histamine concentrations in canine whole blood and plasma were determined under several pharmacological, pathophysiological, and clinical conditions using fluorometric methods.The specificity of the assay for whole-blood histamine was investigated by comparing 3 purification procedures for the isolation of histamine from whole blood including butanol extraction (Shore), ion-exchange chromatography on Dowex 50 W-X 8, and the combination of these 2 methods (Lorenz). Histamine in whole blood was identified in analytical and preparative samples by fluorescence spectra, thin-layer chromatography, degradation by diamine oxidase from pig kidney and inactivation by histamine methyltransferase from guinea-pig brain as well as by biological tests on the isolated guinea-pig ileum. Since butanol extraction resulted in significantly higher 'histamine' values than the other two purification procedures, ionexchange chromatography on Dowex 50 was recommended as the method of choice for the specific determination of histamine in doffs whole blood.Normal values of histamine concentrations in canine plasma were tentatively estimated. They depended on the time between pretreatment of the animals (anaesthesia, operation) and the collection of blood and showed an approximately logarithmic normal distribution. The median, the lower/upper quartiles and the range of the plasma histamine levels obtained 30 minutes after the end of pretreatment were 0.2, 0-0.4 and 0-1.2 ng/ml, respectively. Nearly 50 % of the values were zero (below 0.1 ng according to the sensitivity of the method), only 1 ~ of them exceeded slightly 1 ng/ml. Thus histamine release by drugs or by other medical treatments was only stated, when plasma histamine levels exceeded 1 ng/ml and decreased in a way to give an elimination carve of approximately first-order kinetics (Bateman function).Histamine concentrations in dog's whole blood showed approximately a logarithmic normal distribution. The median, lower/upper quartiles and range were 47, 34/75 and 13-209 ng/ml respectively.

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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.

The subject of histamine release was investigated in 16 volunteers by means of plasma histamine determination after the administration of etomidate, Althesin, propanidid, and Cremophor EL. Althesin and propanidid caused release of histamine in various degrees of frequency. Blood pressure changes were rather pronounced with both anaesthetic agents; tachycardia reached its mavimiim in the first and second minute, which seems to be an argument against histaminp release as the underlying cause of this reaction. Histamine was, indeed, only released to such an extent (with the exception of one borderline case) that no clinical symptoms other than secretion of gastric juice and erythema were to be expected. After the application of etomidate and Cremophor EL an increase in plasma histamine was not detectable. Changes in the differential Wood picture in terms of a decrease in basophils only occurred after Althesin and propanidid; not, however, after etomidate and Cremophor EL. Etomidate is, therefore, the first hypnotic drug for intravenous application which is unlikely to cause chemical histaminp release.