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SUMMARY We have investigated the effect of a bolus injection of atracurium 0.6mg kg−1 on the cardiovascular system in 16 patients undergoing aortocoronary bypass surgery. H1- and H2-receptor antagonists were administered to eight patients before the neuromuscular blocker. A standard anaesthetic was used comprising fentanyl, flunitrazepam, etomidate and enflurane. After administration of atracurium, haemodynamic changes and plasma histamine concentrations were measured at frequent intervals. In the first group, who received only atracurium, a brief but marked decrease in SVR and MAP occurred, accompanied by an increase in Cl, together with a marked increase in plasma concentration of histamine. In the second group, who received H1 and H2-receptor block, there was no decrease in MAP and only a small increase in plasma histamine concentration. However, there were significant changes in SVR and Cl similar to those in the atracurium group.

Clinical observations have shown histamine-typical cardiopulmonary reactions immediately after application of heparin. Heparin is produced from animal tissues, rich in mast cells which contain both heparin and histamine. Heparin in clinical use might therefore still contain considerable amounts of histamine. After mixing heparin with human blood,in vitro, an increase in plasma histamine concentration was observed. Additionally, histamine, in various concentrations, could be detected in different heparin batches and separations.

Essential hypertension and gastrointestinal disease are two of the most common diagnoses made in the doctor's office. Since they may occur simultaneously, the differential therapeutic aspects of the respective therapies are of importance for every general practitioner. However, complex interactions between hypertension and gastrointestinal diseases often make the choice of the most suitable drug difficult. The present article provides an overview of the most common therapeutic regimens, identifies possible interactions, and should help the doctor to select the optimal treatment for the individual patient.

Many hypertensive patients have other, usually long-term diseases. Antihypertensive therapy may interfere with these diseases and their therapies. In the present study, the possible interactions of the ACE-inhibitor perindopril with several of the most common long-term diseases was evaluated.In a multicenter, double-blind, randomized, placebo-controlled trial, the effect of perindopril was evaluated in 490 patients with mild essential hypertension and any one of the following concomitant diseases: hyperlipidemia, type II diabetes mellitus, ischemic heart disease, cardiac arrhythmia, peripheral arterial occlusive disease, nephropathy with proteinuria, chronic obstructive pulmonary disease, or degenerative joint disease treated with nonsteroidal anti-inflammatory drugs (NSAIDs). After a 3-week single-blind placebo run-in, the patients received either perindopril (4 mg/d) or matching placebo for 6 weeks.Blood pressure was effectively reduced by perindopril irrespective of the associated disease. The rate of spontaneously reported side effects was low. Treatment with perindopril was free from adverse interactions with the concomitant diseases and therapies. Moreover, favorable actions could be observed in patients with ischemic heart disease (reduction of maximal ST-segment depression during peak exercise and decrease in the number of angina attacks), in patients with proteinuria (decrease in albuminuria in patients with normal serum creatinine levels), and in patients with NSAID-treatment (increase in prostaglandin E2 concentration in gastric mucosa suggesting gastric cytoprotection).This trial shows that ACE-inhibition with perindopril represents a simple, safe, and effective short-term therapeutic option for the large proportion of patients with mild essential hypertension and concomitant diseases and therapies.

Side Effects of Water-Soluble Contrast Agents in Upper Gastrointestinal Tract J. GMEINWIESER;W. ERHARDT;H. REIMANN;R. BABIC;U. SPECK;B. WENZEL-HORA; Investigative Radiology

In patients in a surgical intensive care unit a controlled clinical trial was performed concerned with the pathophysiological functions of histamine in stress ulcer disease and with the influence of cimetidine prophylaxis on this complication. The commonly used organization of a controlled clinical trial was enforced to be changed by considerable theoretical, ethical and practical difficulties in designing and conducting the study: As a surprising and remarkable result of the study clinically manifest stress ulcers occurred exclusively in our patients in the intensive care unit and among them mainly in those with severy polytrauma and postoperative complications. Cimetidine was highly effective in preventing stress ulceration in severe polytrauma patients. But it seems absolutely unnecessary to distribute this drug in all patients of a surgical intensive care unit like from a cornucopia of happiness.

In a preliminary study high doses of the H1-antagonist clemastine (clem) and the H2-antagonist cimetidine (cim) were used in order to detect the side effects of both drugs on allergic reactions. After pretreatment with clem or clem/cim different guinea pigs were challenged with either OA or histamine. Bronchial obstruction was measured by body plethysmography using a new parameter ('compressed air'). Pretreatment with clem/cim in high doses protected guinea pigs against OA-induced bronchial obstruction much more effectively than H1-receptor antagonism alone; lower cim doses produced insignificant effects. In histamine-challenged animals cim showed no protective effects. In vitro clem/cim caused a marked reduction of histamine release measured in perfused lungs from 16.9 +/- 4.2 ng/ml (eight control cases) to 2.8 +/- 1.7 ng/ml (n = 8). Our preliminary data suggest that high doses of clem/cim can protect sensitized guinea pigs against allergen-induced bronchial obstruction by inhibiting histamine release.

Several preparations of Cremophor El®, several of other non-ionic detergents and several components of Cremophor El 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 El 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.

In fourteen patients with food allergy, intragastral provocation under endoscopical control (IPEC) was performed. In all patients positive immediate-type reactions of the gastric mucosa were observed consisting of oedema, erythema and petechial bleeding. Microscopically, mast cell degranulation was observed and measured by mast cell counts using the o-phthaldialdehyde technique. Concomitantly, tissue histamine content in gastric mucosa decreased significantly after allergen provocation, while there was no change in normal volunteers. Plasma histamine concentration increased in most patients; the increases were most evident in four patients showing mild systemic reactions (urticaria and bronchospasm). The technique described might prove to be useful in establishing the diagnosis in doubtful cases of food allergy.

Intravenous urography using Telebrix was performed on 500 patients. Two hundred patients (group I) received no pre-medication; 300 patients (group II) were premedicated with H1 and H2 receptor antagonists. All patients were examined for signs of contrast reactions, blood pressure, pulse rate and plasma histamine levels. These were measured before and three minutes after the administration of the antihistamine substances and/or the contrast medium, and also at the end of the examination. Following the administration of H1 and H2 receptor antagonists, a slight, transient and insignificant rise in plasma histamine could be demonstrated. Both groups showed a significant rise in plasma histamine levels after the injection of the contrast medium. Although the pre-medicated group contained a higher percentage of high risk patients, there were significantly fewer patients with contrast reactions. Pre-medication with H1 and H2 receptor antagonists in high risk patients is therefore advisable.

Prostaglandins have been shown to prevent the damage to the gastric and intestinal mucosa which has been induced by diverse necrotizing substances. These damaging stimuli increase the liberation of histamine from ast cells. Because of its well known effects on cellular permeability histamine may serve the initial stimulus for mediating cellular damage. The aim of our study was to investigate the effect of misoprostol, a synthetic PGE 1 analog, on tissue histamine concentration and mast cell counts after damage to the gastric mucosa induced by stress, histamine, aspirin and concentrated ethanol in guinea pigs. Misoprostol or its matching placebo were administered intragastrically 3 minutes prior to the ulcerogenic stimulus. After the induction of the injury, the animals were sacrificed, stomachs were examined for ulceration. Gastric and duodenal histamine concentrations were determined. Mast cells from these organs were stained and counted. All four ulcerogenic stimuli resulted in significant gastric ulcer formation. This ulcerogenic action was accompanied by a significant decrease in mucosal histamine concentration and mast cell counts. Misoprostol induced a dose-dependent inhibition of gastric damage, histamine depletion and mast cell destruction. These results indicate that the stabilization of mast cells by misoprostol is an important mechanism for its mucosal protective effects against ulcerogens.

In a double blind crossover experiment in 16 healthy male volunteers, the effects of oral FPL 52694 and a matching placebo upon pentagastrin stimulated gastric acid secretion, gastric mucosal histamine content, and gastric mucosal mast cell count were compared. There was a significant increase in acid secretion, and a fall in tissue histamine and the mast cell count after treatment with the placebo. All these changes were inhibited by FPL 52694, and there was a significant difference between the effects of this compound and the placebo in all three parameters. It is concluded that FPL 52694 caused significant inhibition of acid secretion, and that the likely mechanism of action is by stabilisation of mast cells and inhibition of histamine release.

The hypernephroid carcinoma is the most common tumour of the kidney in adults. Haematuria can occur, even in the early developmental stages. In investigations of 30 patients with-haematuria, radiological examinations were made and the plasma histamine levels were determined in both from the renal artery and vein, the vena cava and the aorta. After nephrectomy, the histamine content of various tissues in different regions of the kidney were investigated. Significant increases of plasma and tissue histamine levels were found in the veins of the tumour-riddled kidney and in the tissue surrounding the tumour. an experimental study on dogs investigated whether or not an injection of histamine into the renal artery would provoke haematuria. Dose-dependent haematuria occurred, which was most pronounced following intra-arterial injection of 25 micrograms/kg of histamine.

The specificity of the fluorometric assay of histamine was studied using three different isolation procedures. Histamine was identified by thin-layer chromatography, enzymatic degradation by diamine oxidase, fluorescence spectra and by two different biological tests. The histamine concentration of many tissues, the whole blood and plasma of young and adult pigs were determined. Especially high histamine contents were found in lung, stomach and small intestinum. The tissues of young animals contained smaller amounts of histamine than those of adult animals. Compound 48/80 and polymyxin B, but not the detergent chremophor E1, released histamine from tissues into the plasma. The gastric mucosa stored histamine, whereas some of the other tissues studied showed decreased histamine concentrations. The pharmacological actions of histamine, betazole, serotonin and kinins on the blood pressure, and the stimulation of exocrine glands in the digestive tract by histamine were studied. Histamine and betazole caused a biphasic blood pressure response in pigs which could explain the increase of blood pressure after injection of 48/80.

Using a specific fluorimetric and biological method, the occurrence and distribution of histamine was investigated in man, various mammals, birds, reptiles, amphibians, bony and cartilaginous fishes, lancelets, tunicates, echinoderms, molluscs, and crustaceans. The amine was identified by the fluorescence spectrum, by specific antihistaminics in the bioassay, by the comparison of the fluorimetric histamine values following three different isolation procedures, and in some tissues also by thin-layer chromatography. Histamine was found in all chordates in considerable concentrations with the exception of the stomachless carp. The distribution of histamine in the body, however, varied largely from species to species. Only the gastric mucosa of all vertebratesinvestigated was relatively rich in histamine. The amine was nearly uniformly distributed in amphibians and fishes, in which only the stomach and partly the intestinum showed higher histamine concentrations than all the numerous other tissues investigated. The distribution of histamine, however, in mammals, birds, and reptiles showed great variations from tissue.to tissue. Organs free from histamine were first found in fishes going backward in the phylogeny. Because of the great variabilities in the distribution of histamine in the body of numerous species which were studied in this investigation, only one hypothesis can be developed with respect to a common physiological significance of histamine: there is a selective accumulation of histamine in the gastric mucosa of all chordates possessing acid-secreting cells and a low concentration of histamine in the gastro-intestinal tract of stomachless fishes. The gastric acid secretion is stimulated by histamine in all vertebrates investigated, whereas in many fishes histamine has no effects on the circulation or on smooth muscles of the gastro-intestinal tract or on the uterus. Thus, stored histamine probably has a specific function in the gastric mucosa, but not a general function, such as the regulation of ubiquitous metabolic processes or the regulation of microcirculation.

The question, whether histamine release has a patho-physiological significance during orthotopic homologous liver transplantation in pigs, was investigated in 31 recipients and donors and in 7 isolated perfused livers. The acute arterial hypotension occurring in the revascularization phase of this operation was greatly diminished by the administration of 2 mg/kg chlorphenoxamine. A significant increase of the plasma histamine concentration during this phase of operation and a strong hypotensive effect of corresponding plasma histamine levels in pigs, as determined after injection of 48/80, also support the view, that histamine release may contribute to critical circulatory situations during liver transplantations. As causes of hsitamine release in various degress during this operation, anaesthesia, manipulations at the stomach and gut, passage of the blood through the extracorporeal by-pass and the ischaemia followed by a sudden warming of the liver were shown. The role of other vasoactive substances and biophysical mechanisms for the development of hypotension in the revascularization phase is discussed, but the significance cannot be determined at this time.

In a clinical study the participation of histamine in the allergenic response of patients with food allergy was investigated. The resting levels of gastric tissue and plasma histamines of 10 patients were slightly higher than the respective values of normal volunteers. 5 minutes after local intragastral allergenic provocation a decline of the mucosal histamine content of the allergen-treated area was noticed. Parallel investigations on the mast cell content of the stomach mucosa revealed a parallel decrease of the o-phthaldialdehyde stained cells, whereas the number of toluidine blue stained cells remained unchanged. These data are in accordance with an antigen-induced IgE-dependent liberation of the mast cell histamine stores.

Die nach Revascularisation eines allogenen Lebertransplantates auftretenden Schocksymptome sind eine Folge von Histaminfreisetzung aus Leber und Dunndarm bei fehlender Abbaufahigkeit des ischamisch geschadigten Transplantates. Die Kenntnis dieser Tatsache und Einleitung entsprechender Masnahmen ist von entscheidender Bedeutung fur den Erfolg einer Lebertransplantation am Schwein.

Bei 100 Patienten wurde das Plasmahistamin vor und nach Gabe von Rontgenkontrastmitteln zur Darstellung der ableitenden Harnwege gemessen. Von normalen Plasmahistaminbasiswerten kam es nach Kontrastmittelgabe im Mittel zu einem Anstieg auf 0,66 ng/ml. Am Ende der Untersuchung (nach 20 min) waren die Plasmahistaminwerte wieder normalisiert.

Fur die klinischen Folgen von Darmhypoxie und -ischamie wurden immer wieder „Darmtoxine“ verantwortlich gemacht, aber nur selten wurden sie chemisch identifiziert und ihre Wirksamkeit auch am gesunden Versuchstier nachgewiesen. Eine Ausnahme hierfur stellt das Histamin-Diaminoxidase-System dar, dessen Wirksamkeit im experimentellen A. mesenterica-Schock bei Hund und Kaninchen weitgehend gesichert werden konnte (4). Bei einem standardisierten Modell der intestinalen Ischamie des Kaninchens sollten nun die Fragen geklart werden, ob Histamin im Efluat des ischamischen Dunndarmes erscheint und ob Histamin und Diaminoxydase-Aktivitat im geschadigten Darm eine Veranderung erfahren.

The plasma histamine levels were reported to increase in early hours of the morning in asthmatic patients. It was supposed that this phenomenon would also be observed in normal volunteers. In this study using twelve normal healthy volunteers the plasma histamine levels were examined in a pharmacokinetic manner. It could be shown that plasma histamine levels flow biorhythmic changes with 3 maxima and 3 minima. The acrophases of the maxima are 12.77 +/- 0.61, 19.33 +/- 0.78 and 5.42 +/- 1.83 h. The most important rise in plasma histamine levels was found in the early hours of the morning representing about 55% of the total histamine available in plasma.

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 intraabdominal 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 premedication 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 tachycardia, hypotension, increased gastric secretion and anaphylactoid reactions could be related to the release of histamine in some circumstances.

Histamine release could be shown in 50% of the dogs suffering from acute haemorrhagic pancreatitis in Pfeffer's preparation. The survival time of these dogs was shorter by about 50% than that of animals without alteration of the plasma histamine levels. The powerful diamine oxidase blocker aminoguanidine diminished the incidence of severe pancreatitis in the dogs without influencing survival time. As in animals treated by saline histamine release could be shown in 50% of the aminoguanidine-treated dogs in which higher plasma histamine levels were determined than in saline-treated animals. The survival time of the dogs with histamine release, however, was not different from that of animals with normal plasma histamine levels throughtout the experiment. The actions of aminoguanidine in Pfeffer's preparation seemed to be rather complex. Contrasting effects on the development of pancreatitis and on histamine inactivation may have influenced the survival time in different directions.

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.

Various lymphocyte populations, dendritic cells and macrophages contribute to the intake of antigen. The transportation of antigen in the intestinal wall is possible with the help of receptive endocytosis, including extracellular protein in fluid droplets, bacterial and vegetable toxins, as well as certain viruses, which seem to be able to penetrate the cell membrane and enter directly into the cell. Own investigations: After endoscope controlled allergy-irritation of the gastro-intestinal tract, 20 people used in the clinical test showed acute signs of mucosal reaction with inflammation and swelling of the mucous membrane as well as haemorrhagic lesions. A histamine release from the mastcell was proved.

Tissue histamine determination in the urogenital tract showed that there are significant differences concerning tissue histamine content between intraoperative and postmortem tissue samples. The difference appeared to be most significant in the case of renal pelvis samples, where the decrease was about 90% in the autopsie material compared to intraoperative tissues. In comparing tissue histamine content in special organs of different animal species we discovered considerable differences; e.g. in the ureter of the dog we measured 30 micrograms/g tissue - where as against the values in man amounted to only 6 micrograms/g tissue. The physiological meaning of the different tissue histamine levels is unknown.

Prior to cannulation for extracorporeal circulation, 375 Units of Heparin/kg body weight were applied to 22 patients (group 1) into the right atrium. A few minutes later, characteristic changes in haemodynamics were observed. In a second group of 10 patients, the same amount of heparin was injected directly into the ascending aorta to avoid the passage of an undiluted bolus of heparin through the pulmonary vessels. In this group, the haemodynamic effects of heparin seemed to be slightly weakened. Immediately after administration of heparin, a significant increase of plasma histamine was measured (in 12 patients of group 1). This might be the main reason for the heparin-dependent haemodynamic effects.

Das ideale Nahtmaterial sollte folgende Eigenschaften haben: gleichbleibende Elastizitat, Inertheit im infizierten Gewebe, keinen negativen Einflus auf die Wundheilung sowie eine leichte Handhabung. Diesen Anforderungen entspricht am ehesten monofil rostfreier Stahl mit zwei Einschrankungen: steife Handhabung und Reizung durch Fadenenden. Seide, Baumwolle und Catgut haben folgende Nachteile: Einmal Abszesbildung und zum andern Epitheleinsprossungen. So hielt die Suche nach gewebefreundlichen Materialien an. Nach der Entdeckung des „Nylon“ 1938 wurde Polyamid 1960 in Form eines ungefarbten Fadens von 40 μm ∅ in die Ophthalmologie eingefuhrt. Seit 1963 wird ein schwarzgefarbter 30 μm ∅ starker Nylonfaden fur die Corneachirurgie von Harms und Mackensen (1966) empfohlen. Wie aus vielen Untersuchungen (Velhagen, 1956; Schmitt und Doden, 1972; Doden und Schmitt, 1974) hervorgeht, treten physikalisch Schrag-, Quer- und Langsbruche sowie Verdunnungen des Nylonfadens auf. Chemisch ist durch eine Hydrolyse eine Depolymerisierung und damit eine Schadigung durch Monomere moglich. Es wundert uns, das Polypropylen, das bereits 1961 in die Chirurgie eingefuhrt wurde und eine sehr gute Gewebevertraglichkeit mit hoher Knotenfestigkeit vereinte, erst 1970 am Musculus rectus superior des Kaninchenauges und an der palpebralen Conjunctiva verschiedener Versuchstiere angewendet wurde (Ulin, 1970). Chemisch ist es aus isotaktischem Polypropylen aufgebaut. Es gehort zu den hydrophobsten synthetischen Fasern und absorbiert weniger als 0,1% Wasser. Die Reisfestigkeit ist hoher als bei Nylon.

From a methodological point of view the relevance of clinical-biochemical trials depends on the answers to mainly four complexes of questions: (1) the reliability of the assays in the clinical situation to be tested, (2) the precision and accuracy of sample-taking, (3) the qualification of the design and the protocols in the clinical part of the trial and (4) the usefulness of the time concepts in the trial concerning biorhythms, seasonal influences, psychological trauma of diagnostic procedures and treatment. In this study mainly the second complex of questions was studied intensely. The precision of the fluorometric histamine assay in biopsy specimens from human gastric mucosa depended on several conditions: Biochemical technique, sample preparation and removal of biopsies from gastric mucosa via endoscopy. The CV% of the whole procedure was about 8-times higher than that of the biochemical technique. In clinical-biochemical studies on the significance of histamine or any other hormone (such as gastrin) in any disease (uch as duodenal ulcer) it seems therefore useless to describe the precision of an assay only by the variance of the biochemical technique. Calculation of the histamine content as mean of 3 samples reduced the CV% from 27.2 to 14.9% and should therefore be recommended.

This study demonstrates a very rapid and short-lasting elevation of plasma histamine concentrations after heparin injection prior to cannulation for extracorporeal circulation during cardiac surgery. Plasma histamine concentrations increased significantly for less than 1 min following bolus injection of heparin into the right atrium. Blood samples were taken from the distal pulmonary vascular bed, i.e. the pulmonary vein. The design of the study enabled us to observe the development of plasma histamine concentrations within very short time intervals and to detect the high peak plasma histamine concentration that may occur, primarily in the pulmonary outstream vessels. Therefore, the histamine found here could originate from intrathoracically located mast cells. It is more likely, however, that the histamine was administered together with the heparin in complex binding, due to purification problems. The amount of histamine found in this study was sufficient to produce mild to severe circulatory effects in all patients receiving a high dose of heparin.

Die Bedeutung von Histamin in der Stresulcuspathogenese des Menschen ist in letzter Zeit mehr und mehr erkannt worden. Nach schweren Belastungen des Organismus, wie Polytrauma, Verbrennung und ausgedehnten Operationen, kommt es zu solchen Erhohungen der Plasmahistaminkonzentration, wie sie auch bei i.v. Applikation des Amins im „augmented histamine test“ zu hamorrhagischen Erosionen der Magenschleimhaut fuhren (3, 3). Auserdem haben, sich Histamin-H2-Receptorenantagonisten in der Therapie des Stresulcus bereits in kontrollierten Studien bewahrt (3). Deshalb wurde gepruft, ob beim Immobilisationsstres, der zu akuten Magenlasionen bei der weiblichen Ratte fuhrt, die Histamingehalte der Magenschleimhaut und verschiedener anderer Organe sich signifikant verandern.

Stimulation tests (pentagastrin) induced significant changes in tissue histamine levels in the gastric mucosa within 30 minutes. Acid secretion and a decrease of histamine after application of antacids containing calcium could not be observed in our study; neither was application of antacids over a period of eight days followed by a change in gastric mucosal tissue histamine concentrations. Patients under non-steroidal antiphlogistic medication showed diminished histamine levels. Administration of antacids did not produce changes in histamine levels, but induced a rise of PGE2 levels in the fundal and corpus area of the stomach. This may be due to a cytoprotective effect of antacids containing calcium on the gastric mucosa.

In 1936 Selye et al. [1] defined stress as a state of being, whereby the tension upon the organism mobilizes its power of resistance in order to meet a threatening situation. Each factor that can produce such an effect is called a Stressor.

During intestinal ischemia in rabbits histamine concentration and diamine oxidase activity were altered in the intestinal wall and in the perfusate of mesenteric vessels. The results were interpreted as a histamine release and an increased catabolism of diamine oxidase. Thus, the combination of release of vasoactive histamine and partial elimination of a protective enzyme may contribute to the fatal outcome after mesenteric ischemia.

Several reports, dealing with typical cardiovascular reactions immediately after injection of heparin during cardiac surgery, have been presented. A possible reason for these reactions is a short-lasting elevation of plasma histamine concentration following heparin injection. As most types of heparin contain antibacterial preservatives such as benzyl alcohol, which can cause adverse reactions, both substances, heparin itself and the preservative, can theoretically be responsible for this reaction. Therefore, this study was carried out in order to measure the effects of preservative-free heparin on plasma-histamine levels and on hemodynamic parameters. It became evident that preservative-free heparin also entails characteristical hemodynamic effects, such as a decrease in arterial mean pressure and peripheral vascular resistance as well as an increase in cardiac output. A significant increase in plasma-histamine concentration could be shown 20-120 seconds after injection of heparin. We conclude that benzyl alcohol is not the major reason for the hemodynamic effects and elevation of plasma-histamine concentration, following heparin injection, but we cannot exclude that benzyl alcohol does in fact play a minor role. The results of this study suggest that the cardiovascular reactions and the elevation of plasma histamine concentration following heparin injection are heparin-specific phenomena.

Histamin kontrahiert den Ureter dosisabhangig, Histamin-HrAntagonisten schwachen kompetitiv die Ureterkontraktionen [1]. Wird nach Unterbindung der Ureter Histamin in die Arteria renalis appliziert, steigt der bereits erhohte Druck im gestauten Nierenbecken noch weiter an, umgekehrt wird er durch Histamin-H1- und vor allem H2-Rezeptorantagonisten gesenkt [3]. In der vorliegenden Studie wurde daher gepruft, ob Steinkoliken durch Antihistaminika unterbrochen und ein Steinabgang erleichtert werden kann.

In the glandular part of the stomach, the histamine content was significantly increased during stress by immobilization. Following 8 hours of restraint these alterations were observed only in lung tissue, but not in other organs investigated. Although the maximum of stress ulcer formation did not correspond with the maximum increase in gastric histamine content as far as the time course is concerned, a role of histamine in stress ulcer disease cannot be excluded.