dinoprost and Anaphylaxis

Topics: Anaphylaxis; Animals; Asthma; Bronchi; Dinoprost; Dinoprostone; Dogs; Epoprostenol; Guinea Pigs; Humans; In Vitro Techniques; Lung; Lung Diseases; Models, Biological; Muscle, Smooth; Prostaglandin D2; Prostaglandins; Prostaglandins D; Prostaglandins E; Prostaglandins F; SRS-A; Thromboxane A2

Drugs can interfere with the immune system in two basically different ways: (1) they may interact with the specific recognition mechanisms of the immune system and thus induce an allergic response that is specific for the offending agent; (2) drugs may exert pharmacological effects on the immune systems which result in a response that is independent of its recognition structures or they may activate effector and amplification mechanisms that are normally triggered by specific immune processes. Allergic reactions to drugs are different from reactions that exhibit the same clinical symptoms but lack the specificity of an allergic reaction to the offending agent. It has been suggested that those non-specific reactions which mimic the signs and symptoms of allergic reactions should be classified as pseudo-allergic reactions (PAR). PAR are characterized by the following properties which differentiate them from allergic reactions. (1) The symptoms of PAR are qualitatively different from the pharmacological response of a drug and are not related to adverse reactions connected with its pharmacological and toxicological profile. (2) PAR are not specific with regard to the chemical structure of the triggering agent. (3) PAR lack transferability to other subjects of the same species. (4) In contrast to the allergic reactivity, the pseudo-allergic reactivity is not acquired but genetically predetermined. (5) Pseudo-allergic reactivity is often expressed upon the first contact with an eliciting agent. PAR are thus an expression of a pharmacological interaction of drugs or their metabolites in genetically predisposed individuals.

Topics: Anaphylaxis; Aspirin; Complement Activation; Complement System Proteins; Cyclooxygenase Inhibitors; Dinoprost; Dinoprostone; Drug Hypersensitivity; Epitopes; Female; Histamine; Histamine Release; Humans; Immunosuppression Therapy; Lupus Erythematosus, Systemic; Prostaglandins E; Prostaglandins F

Topics: Adenylyl Cyclases; Anaphylaxis; Animals; Asthma; Bronchi; Chemical Phenomena; Chemistry; Dinoprost; Guinea Pigs; Lung; Lung Diseases; Prostaglandin-Endoperoxide Synthases; Prostaglandins; Prostaglandins E; Prostaglandins F; Structure-Activity Relationship; Trachea

Topics: Adolescent; Anaphylaxis; Anti-Inflammatory Agents, Non-Steroidal; Dinoprost; Drug Hypersensitivity; Female; Humans; Leukotriene E4; Prostaglandin D2; Salicylamides

The role of arachidonic acid metabolites in NSAID-induced hypersensitivity has been studied in depth for NSAID-exacerbated respiratory disease (NERD) and NSAID-exacerbated cutaneous disease (NECD). However, no information is available for NSAID-induced urticarial/angioedema (NIUA), despite it being the most frequent clinical entity induced by NSAID hypersensitivity. We evaluated changes in leukotriene and prostaglandin metabolites for NIUA patients, using patients with NECD and single-NSAID-induced urticaria/angioedema or anaphylaxis (SNIUAA) for comparison.. Urine samples were taken from patients with confirmed NSAID-induced urticaria and healthy controls, at baseline and at various time intervals after ASA administration. Eicosanoid measurement was performed using high-performance liquid chromatography-tandem mass spectrometry and gas chromatography-mass spectrometry.. No differences were found between groups at baseline. Following ASA administration, LTE4 and 9α,11β-PGF2 levels were increased in both NIUA and NECD patients compared to baseline, rising initially, before decreasing toward initial levels. In addition, the levels of these metabolites were higher in NIUA and NECD when compared with the SNIUAA and control groups after ASA administration. No changes were found with respect to baseline values for SNIUAA and control groups.. We present for the first time data regarding the role of COX-1 inhibition in NIUA. Patients with this entity show a similar pattern eicosanoid levels following ASA challenge to those with NECD. Further studies will help ascertain the cell populations involved and the underlying molecular mechanisms.

Topics: Administration, Oral; Adolescent; Adult; Anaphylaxis; Angioedema; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Cyclooxygenase 1; Cyclooxygenase Inhibitors; Dinoprost; Drug Hypersensitivity; Eicosanoids; Female; Humans; Leukotriene E4; Male; Middle Aged; Phenotype; Young Adult

Topics: Abdominal Pain; Adult; Anaphylaxis; Angioedema; Anti-Asthmatic Agents; Biomarkers; Cromolyn Sodium; Diarrhea; Dinoprost; Female; Histamine Antagonists; Humans; Leukotriene E4; Male; Mast Cells; Mastocytosis; Middle Aged; Omalizumab; Prostaglandin D2; Treatment Outcome; Tryptases; Urticaria

Anaphylaxis is a life-threatening hypersensitivity reaction. To identify biomarkers for the condition, we assessed serum levels of apolipoprotein (Apo)A and ApoE. We found a reduction of both lipoproteins in anaphylactic mice as well as in orally challenged food allergic patients. We then compared patients after acute anaphylaxis with several control groups (nonallergic, history of allergen-triggered anaphylaxis, acute cardiovascular/febrile reactions). In this unpaired setting, ApoE levels were unaltered, while ApoA1 was reduced in the anaphylactic group. Although unable to discriminate between anaphylaxis and cardiovascular/febrile reactions, ROC curve analysis revealed a reasonably high area under the curve (AUC) of 0.91 for ApoA1. Serum 9α,11ß-PGF

Topics: Anaphylaxis; Animals; Apolipoprotein A-I; Area Under Curve; Biomarkers; Dinoprost; Humans; Mice; Predictive Value of Tests; ROC Curve

Topics: Anaphylaxis; Biomarkers; Cysteine; Dinoprost; Female; Histamine; Humans; Leukotrienes; Male; Tryptases

Anaphylactic shock is associated with severe hypotension. Potassium channel blockers, such as 4-aminopyridine, induce vasoconstriction. The objective of this study was to test the ability of 4-aminopyridine to restore blood pressure and increase survival in anaphylactic shock.. Experimental study.. Physiology laboratory.. Adult male Wistar rats.. Rats were sensitized with ovalbumin (1 mg SC), and anaphylactic shock was induced by IV injection of ovalbumin (1 mg). Experimental groups included non-allergic rats (NA) (n = 6); allergic rats (Controls) (n = 6); allergic rats treated with 4-aminopyridine (4-aminopyridine) (1 mg/kg) (n = 6); and allergic rats treated with epinephrine (EPI) (10 µg/kg) (n = 6). Treatments were administered 1 minute after induction of anaphylactic shock.. Mean arterial blood pressure, heart rate, and survival were measured for 60 minutes. Plasma levels of histamine, leukotriene B4, prostaglandin E2, prostaglandin F2, pH, and HCO3 were measured. Mean arterial blood pressure was normal in the NA group; severe hypotension and high mortality were observed in controls; normalization of mean arterial blood pressure, heart rate, and increased survival were observed in 4-aminopyridine and EPI groups. All allergic 4-aminopyridine-treated rats survived after the induction of anaphylactic shock. Histamine level was higher in controls and the 4-aminopyridine group but reduced in the EPI group. Prostaglandin E2 increased in controls and EPI group and decreased in 4-aminopyridine group; prostaglandin F2 increased in controls but decreased in 4-aminopyridine and EPI groups. Leukotriene B4 decreased in 4-aminopyridine and EPI groups. Metabolic acidosis was prevented in the 4-aminopyridine group.. Our data suggest that voltage-dependent K+ channel inhibition with 4-aminopyridine treatment restores blood pressure and increases survival in the Wistar rat model of anaphylactic shock. 4-aminopyridine or related voltage-dependent K channel blockers could be a useful additional therapeutic approach to treatment of refractory anaphylactic shock.

Topics: 4-Aminopyridine; Acidosis; Anaphylaxis; Animals; Blood Pressure; Dinoprost; Dinoprostone; Disease Models, Animal; Epinephrine; Heart Rate; Histamine; Leukotriene B4; Male; Potassium Channel Blockers; Rats, Wistar; Vasoconstrictor Agents

Allergens can induce anaphylactic shock and death due to serve hypotension. Potassium channel blockers (K(+)(ATP)) such as glyburide (GLY) induce vasoconstriction. The effect of (K(+)(ATP)) channel blockers on anaphylactic shock is poorly understood. Objective of the study was to test the hypothesis that GLY reduces hypotension induced in anaphylactic shock and increases survival. Rats were grouped into: G1-N=Naïve; G2-SC=Sensitized-Control; G3-SG=Sensitized-GLY (glyburide 40 mg/kg); G4-SE=Sensitized-EPI (epinephrine 10 mg/kg). G2 to G4 groups were sensitized with ovalbumin (OVA) and shock was induced by i.v. injection of OVA. Treatments were administered intravenously 5 min later. Mean arterial pressure (MAP), heart rate (HR), and mean survival time (MST) were measured for 60 min following OVA injection and treatments administration. At the end of the experiment, blood withdrawal was performed to measure plasma levels of histamine, leukotriene B(4) (LTB(4)), prostaglandin E(2) (PGE(2)) and prostaglandin F(2) (PGF(2)). Additionally blood gas (paO2, paCO2, SaO2) and electrolytes (Na(+), K(+) and Ca (++)) were measured. MAP was normal in G1-N; severe hypotension, negative inotropic and short MST were observed in G2-SC; normalization of MAP, with lesser negative inotropism and increased MST were observed in G3-SG; full recovery was observed in G4-SE. Histamine level was significantly higher in G2-SC; reduced in G3-SG and G4-SE. PGE(2) increased in G3-SG; PGF(2) increased in G2-SC and G3-SG. Na(+) and Ca (++) concentration decreased in sensitized rats but reversed in treated groups, without change in K(+) concentration. In conclusion, our data suggest that administration of GLY reduced hypotension and increases survival time in rat anaphylactic shock.

Topics: Allergens; Anaphylaxis; Animals; Arterial Pressure; Dinoprost; Dinoprostone; Glyburide; Heart Rate; Histamine; Hypotension; Leukotriene B4; Male; Ovalbumin; Potassium Channel Blockers; Rats; Rats, Wistar

It has recently demonstrated that a free radical-mediated pathway generates prostaglandins (PGs) and the corresponding prostaglandin enantiomers (ent-PGs). Aspirin-intolerant asthma and anaphylaxis accompany PGD(2) overproduction, possibly associated with mast cell activation via the COX pathway. However, free radical-mediated PG generation in the pathophysiology of these diseases, which can be demonstrated by measuring urinary ent-PGF(2)alpha, has not been reported.. To evaluate the characteristic profile of eicosanoid generation via the COX and/or free radical-mediated pathway underlying aspirin-intolerant asthma and anaphylaxis.. A comparative group analysis consisted of asthma (n = 17) and anaphylaxis (n = 8, none with aspirin-induced anaphylaxis) cases. Urinary eicosanoid concentrations were quantified as follows: 2,3-dinor-9alpha,11beta-PGF(2) by gas chromatography-mass spectrometry; leukotriene E(4), 9alpha,11beta-PGF(2), and PGs by enzyme immunoassay.. 2,3-Dinor-9alpha,11beta-PGF(2) is a more predominant PGD(2) metabolite in urine than 9alpha,11beta-PGF(2). At baseline, the aspirin-intolerant asthma group (n = 10) had significantly higher leukotriene E(4) and lower PGE(2) concentrations in urine than the aspirin-tolerant asthma group. During the reaction, the urinary concentrations of leukotriene E(4) and PGD(2) metabolites correlatively increased, but with markedly different patterns of the mediator release, in the aspirin-intolerant asthma group and the anaphylaxis group, respectively. The urinary PGD(2) metabolites and primary PGs were significantly decreased in the aspirin-tolerant asthma group. Urinary ent-PGF(2)alpha concentrations were significantly increased in the anaphylaxis group but not the aspirin-intolerant asthma group.. When assessed by urinary 2,3-dinor-9alpha,11beta-PGF(2), PGD(2) overproduction during aspirin-intolerant bronchoconstriction was clearly identified, regardless of COX inhibition. It is evident that free radical-mediated PG generation is involved in the pathophysiology of anaphylaxis.

Topics: Adult; Aged; Anaphylaxis; Aspirin; Asthma; Biomarkers; Bleeding Time; Cysteine; Dinoprost; Eicosanoids; Female; Humans; Leukotrienes; Male; Middle Aged; Young Adult

Anaphylaxis is a life-threatening syndrome resulting from the sudden release of mast cell- and basophil-derived mediators into the circulation. However, pathological evidence of the association between inflammatory mediators and human anaphylaxis is insufficient.. The aim of this study was to better understand the relationship between in vivo production of inflammatory mediators and the pathogenesis of anaphylaxis. We also sought to evaluate mast cell activation in anaphylaxis.. We measured the concentrations of various inflammatory mediators in urine samples, which were collected from 32 anaphylactic patients during the onset of anaphylaxis and during clinical remission, 21 patients with asthma on acute exacerbation and 15 healthy control subjects. Blood and urine specimens were collected from the patients after provocation test. Urinary leukotriene E4 (LTE4), 9alpha, 11beta-prostaglandin F2 (9alpha, 11beta-PGF2), eosinophil-derived neurotoxin (EDN) and leukotriene B4 glucuronide (LTBG) concentrations were determined by enzyme immunoassay, and the activity of plasma platelet-activating factor acetylhydrolase and serum tryptase concentration were measured using commercially available kits.. Significantly higher concentrations of urinary LTE4 and 9alpha, 11beta-PGF2, which immediately decreased during clinical remission, were observed in the anaphylactic patients than in asthmatic patients on acute exacerbation and healthy control subjects. Concentrations of EDN and LTBG were not significantly different among the anaphylactic patients, asthmatic patients on acute exacerbation and healthy subjects. There was a significant correlation between urinary LTE4 and 9alpha, 11beta-PGF2 concentrations in the anaphylactic patients (r=0.672, P=0.005, n=32). In addition, LTE4 concentration in patients with anaphylactic shock is significantly elevated compared with that in patients without anaphylactic shock.. This is a report on the significant increase in urinary LTE4 and 9alpha, 11beta-PGF2 concentrations during anaphylaxis. Urinary LTE4 and 9alpha, 11beta-PGF2 concentrations may be a reliable marker of endogenous production of inflammatory mediators associated with anaphylaxis.

Topics: Adolescent; Adult; Anaphylaxis; Asthma; Cysteine; Dinoprost; Female; Humans; Inflammation Mediators; Leukotriene E4; Leukotrienes; Male; Mast Cells; Middle Aged; Prostaglandin D2; Young Adult

8-Iso-prostaglandin F2alpha, release from isolated and perfused guinea-pig lung was measured by radioimmunoassay. 8-Iso-prostaglandin F2alpha release was detectable under basal conditions and increased 10-fold during antigen-induced bronchoconstriction, concomitant with the increase of thromboxane B2 and prostaglandin E2. The anti-8-iso-prostaglandin F2alpha serum used in the radioimmunoassay seems to be quite specific for this compound. Pretreatment of lungs with indomethacin (a non-selective inhibitor of cyclooxygenase) reduced 8-iso-prostaglandin F2alpha release under basal conditions and completely abolished the increase observed during lung anaphylaxis. Pretreatment of lungs with NS 398 (N-[2-cyclohexyl]-4-nitrophenyl methanesulphonamide), a selective inhibitor of cyclooxygenase-2, did not change basal or antigen-induced 8-iso-prostaglandin F2alpha release at all. We conclude that under basal conditions guinea-pig lung perfusates contain low levels of 8-iso-prostaglandin F2alpha-like immunoreactivity, which increase 10-fold during antigen-induced bronchoconstriction. This isoprostane seems to be derived from the cyclooxygenation of arachidonic acid via the constitutive form of cyclooxygenase.

Topics: Anaphylaxis; Animals; Bronchoconstriction; Cyclooxygenase Inhibitors; Dinoprost; Dinoprostone; F2-Isoprostanes; Guinea Pigs; In Vitro Techniques; Indomethacin; Lung; Male; Nitrobenzenes; Ovalbumin; Sulfonamides; Thromboxane B2

Isolated hearts from ovalbumin sensitized guinea-pigs were perfused according to Langendorff. Ovalbumin injection decreased coronary flow. Left ventricular pressure amplitude and heart rate increased initially and decreased thereafter. Concomitantly, the liberation of histamine, prostaglandin F2 alpha, as well as the sum of leukotrienes C4/D4/E4/F4, measured in the perfusate by radioimmunoassay, was augmented. Staurosporine (1 microM), an inhibitor of protein kinases, did not influence the liberation of mediators in response to antigen challenge, but inhibited all mechanical responses. Infusion of phorbol myristate acetate, an activator of protein kinase C, into non-sensitized hearts decreased coronary flow and left ventricular pressure amplitude, but did not liberate mediators. Staurosporine (1 microM) abolished these mechanical responses. The results indicate that staurosporine suppresses cardiac anaphylaxis by blockage of mediator effects rather than by inhibition of liberation or formation of mediators.

Topics: Alkaloids; Anaphylaxis; Animals; Arachidonic Acids; Coronary Circulation; Dinoprost; Female; Guinea Pigs; Heart; Heart Rate; Hemodynamics; Histamine Release; In Vitro Techniques; Leukotrienes; Male; Ovalbumin; Radioimmunoassay; Staurosporine; Tetradecanoylphorbol Acetate; Ventricular Pressure

A series of cases of sudden unexpected post-neonatal deaths from two centres in the UK have been investigated for evidence of mast cell activation using the biochemical markers tryptase and 9 alpha,11 beta-PGF2. Tryptase was selected as a possible marker because it is a component of mast cell secretory granules and, unlike histamine, it is not released from basophils. The prostaglandin 9 alpha,11 beta-PGF2 is an initial and pharmacologically active metabolite of PGD2, the major mast cell-derived cyclooxygenase product. This prostaglandin was chosen to serve as a marker of newly generated mediator release. In the study, unexplained infant deaths were associated with a higher concentration of tryptase in serum compared with cases of unexpected, but subsequently explained death. However, 9 alpha,11 beta-PGF2 was found to be an unsuitable post mortem marker in this situation. These results provide direct evidence that mast cell degranulation, possibly as a result of anaphylaxis, may be occurring around the time of death in some cases of cot death.

Topics: Anaphylaxis; Antibodies, Monoclonal; Biomarkers; Cell Degranulation; Child, Preschool; Chymases; Dinoprost; Humans; Immunoenzyme Techniques; Infant; Infant, Newborn; Mast Cells; Serine Endopeptidases; Sudden Infant Death; Tryptases

Our previous studies have shown that the inhibition of neutral endopeptidase, an enzyme which degrades tachykinins, increases anaphylactic contraction of guinea pig tracheal smooth muscle. Anaphylactic release of tachykinin-like substances was indicated. To investigate this observation further, we examined the effects of phosphoramidon, an inhibitor of a neutral endopeptidase, on contraction induced by mediators of anaphylaxis. Phosphoramidon significantly increased histamine- and leukotriene D4-induced contractions of tracheal rings from unsensitized animals (by 14 and 48%, respectively), but failed to alter the contractile responses to prostaglandins D2 and F2 alpha. In tracheal rings preincubated with tachykinin antagonist-[D-Pro4, D-Trp7,9]-substance P(4-11), or in capsaicin-desensitized tracheal rings, phosphoramidon did not change histamine- and leukotriene D4-induced contractions. In the second part of the study, performed on tracheal rings obtained from ovalbumin-sensitized guinea pigs, we examined the effects of phosphoramidon on contractile responses to histamine and leukotrienes which are released after antigen challenge. The incubation of tracheal rings with H1-histamine receptor antagonist (diphenhydramine HCl) or leukotriene receptor antagonist (ICI 198.615) prevented a phosphoramidon-dependent increase of antigen-induced contraction. These results indicate that histamine and leukotrienes may be involved in the anaphylactic release of tachykinin-like substances or other neutral endopeptidase substratum.

Topics: Anaphylaxis; Animals; Antigens; Dinoprost; Diphenhydramine; Glycopeptides; Guinea Pigs; Histamine; In Vitro Techniques; Indazoles; Leukotriene D4; Muscle Contraction; Muscle, Smooth; Neprilysin; Prostaglandin D2; SRS-A; Trachea

The symptoms and hemodynamic alterations that accompany episodes of systemic mast cell activation have been largely attributed to excessive prostaglandin (PG)D2 release. Quantification of the major urinary metabolite of PGD2 has been invaluable in elucidating a role for PGD2 in these clinical entities and in the biochemical evaluation of systemic mastocytosis. With the use of a modified mass spectrometric assay for the major urinary metabolite of PGD2, this metabolite was detected in plasma from 10 normal volunteers (3.5 +/- 1.4 pg/ml). Ingestion of niacin, which induces endogenous release of PGD2, increased plasma levels of this metabolite 6.3 to 33 times above the upper limit of normal by 2 hours. Thereafter, levels declined gradually but remained elevated for up to 6 to 8 hours. In contrast, circulating levels of 9 alpha, 11 beta-PGF2, the initial metabolite of PGD2, peaked by 30 minutes and returned to baseline by 2 hours. The clinical utility of measuring the major urinary metabolite in the circulation was demonstrated by detection of markedly increased levels in plasma and serum from patients with systemic mastocytosis and a patient with a severe type I allergic reaction. Thus in the biochemical evaluation of episodes of systemic mast cell activation and endeavors to further elucidate the role of PGD2 in human disease, there are kinetic advantages of measuring the major urinary metabolite of PGD2 in the circulation. One particular advantage is the evaluation of clinical events, which only in retrospect are suspected to be associated with excessive release of PGD2, yet plasma or serum was obtained proximate to the event.

Topics: Anaphylaxis; Dinoprost; Drug Stability; Drug Storage; Female; Humans; Kinetics; Male; Mastocytosis; Niacin; Prostaglandin D2; Prostaglandins D; Time Factors; Urticaria Pigmentosa

A middle-aged woman developed recurrent episodes of severe life-threatening anaphylaxis. All episodes were strikingly associated with the first day of menstrual bleeding. Temporary relief was achieved with indomethacin therapy. The patient fully recovered following abdominal hysterectomy and salpingoophorectomy. The possible role of sex hormones and prostaglandin F2 alpha in the pathogenesis of this problem is discussed.

Topics: Adult; Anaphylaxis; Dinoprost; Female; Humans; Menstruation; Progesterone

In this paper we report an inhibitory effect of (-)-baclofen on many models of bronchial hyperreactivity both in vivo and in vitro. (-)-Baclofen protects guinea-pigs from the anaphylactic bronchospasm induced in sensitized animals by an ovalbumin aerosol and from that induced by aerosols of histamine and PGF2 alpha. Moreover (-)-baclofen reduces the TXA2 and TXB2 output induced by ovalbumin from isolated sensitized guinea-pig lungs. On the other hand (-)-baclofen does not show antihistaminic, anticholinergic or antiprostaglandinic action on isolated tracheal preparations. It is concluded that baclofen can provide protection from bronchial hyperreactivity possibly through a modulation of autonomic nervous system activity.

Topics: Acetylcholine; Anaphylaxis; Animals; Baclofen; Bronchial Spasm; Dinoprost; Guinea Pigs; Histamine Antagonists; Lung; Male; Prostaglandins F; Thromboxane A2; Thromboxane B2

The relative activities of three bronchoconstrictive mediators of anaphylaxis, prostaglandin (PG) D2, PGF2 alpha and histamine, were investigated in anesthetized dogs using two different measures of peripheral lung reactivity: resistance to flow through collateral airways (Rcoll) and dynamic lung compliance (Cdyn). In the collateral system, the three agonists exhibited approximately 3-fold differences in their relative activities when administered by rapid injection into the superior vena cava, with PGD2 greater than PGF2 alpha greater than histamine. PGD2 was approximately three times more active than PGF2 alpha in reducing Cdyn, whereas responses to PGF2 alpha and histamine were equivalent. These relationships were unchanged in vagotomized animals. Pretreatment with atropine (1 mg/kg) significantly attenuated changes in Rcoll, but had only small and inconsistent effects on changes in Cdyn. Although the time to initial response in both measures of peripheral airways reactivity was similar, the time to maximal response in Rcoll was approximately twice that of Cdyn. In lung parenchymal strips, the rank order of contractile activity of the three mediators was opposite that observed in the peripheral airways in vivo. These data demonstrate that airflow through the collateral system can be modulated by mediators of anaphylaxis in the pulmonary circulation and suggest that such mediators may influence ventilation/perfusion relationships in the lung periphery through their differential effects on peripheral airways and other parenchymal contractile elements. The present study also indicates that the determinants of flow through the collateral system exhibit certain basic pharmacologic and physiologic differences from those of Cdyn and suggests that these two measures of peripheral airways reactivity are not equivalent.

Topics: Airway Resistance; Anaphylaxis; Animals; Dinoprost; Dogs; Dose-Response Relationship, Drug; Female; Histamine; In Vitro Techniques; Lung; Lung Compliance; Male; Muscle Contraction; Prostaglandin D2; Prostaglandins D; Prostaglandins F; Respiration; Vagotomy

Within the last few years intra-amniotic (i.a.) instillation of prostaglandin F2 alpha (PGF2 alpha) has become the predominant method of second-trimester abortion in Denmark. The method is employed by nearly all the gynecological departments, where approximately 500 such procedures are carried out annually. Our own investigations have demonstrated that it is necessary to be somewhat restrictive in the administration of supplementary intravenous infusion of oxytocin. It is pointed out, illustrated by four case histories, that there is a potential risk of greater or smaller quantities of i.a. PGF2 alpha accidentally passing during the procedure to the circulation of the patient. This may result in circulatory collapse, among other things, possibly as a result of acute pulmonary hypertension. A number of safety measures are suggested to minimize this risk and to ensure effective treatment should such complications occur.

Topics: Abortifacient Agents, Nonsteroidal; Abortion, Induced; Adult; Amnion; Anaphylaxis; Carboprost; Cardiovascular Diseases; Denmark; Dinoprost; Drug Evaluation; Female; Humans; Oxytocin; Pregnancy; Pregnancy Trimester, Second; Prostaglandins F; Saline Solution, Hypertonic

Topics: Alprostadil; Anaphylaxis; Animals; Dinoprost; Guinea Pigs; Lung; Male; Prostaglandins; Prostaglandins E; Prostaglandins F; Pulmonary Edema

Antigen challenge of passively sensitized chopped human lung resulted in the generation of several arachidonic acid cyclooxygenase metabolites (AACM): thromboxane A2 (TxA2) as measured by its stable metabolite TxB2, prostaglandin D2 (PgD2), prostacyclin (PgI2) as measured by its stable metabolite 6-keto-PgF1 alpha, prostaglandin F2 alpha (PgF2 alpha), and prostaglandin E (PgE). The kinetics of AACM release after antigen challenge paralleled histamine release. All AACM were released in an antigen dose-dependent manner and reached maximal release at antigen concentrations lower than those required for maximal histamine release. Quantitatively, of the AACM measured, PgD2 and PgI2 were found to predominate in anaphylactic reactions of human lung parenchyma. Generation of PgD2 and PgI2 were 3- to 7-fold greater than that of other AACM measured. Thromboxane B2 was generated in quantities comparable to PgE and PgF2 alpha. Studies were designed to test the hypothesis that lung smooth muscle contraction per se can account for the generated AACM that are released during anaphylaxis of the lung. The studies compared antigen-induced AACM generation with methacholine-induced (10(-4) M) AACM generation. The failure to confirm this hypothesis was especially evident for PgD2 where release was dependent on mast cell activation. Thromboxane A2, PgD2, and PgI2 have been reported to have potent effects on smooth muscle. Our data suggested that these AACM are generated in such sufficient quantities that they may function in important aspects of the modulation of hypersensitivity responses in human lungs.

Topics: Anaphylaxis; Antigens; Arachidonic Acid; Arachidonic Acids; Dinoprost; Epoprostenol; Histamine Release; Humans; In Vitro Techniques; Lung; Mast Cells; Methacholine Compounds; Muscle Contraction; Muscle, Smooth; Prostaglandins; Prostaglandins D; Prostaglandins E; Prostaglandins F; Thromboxane A2; Thromboxanes