Dexamethasone and indomethacin modify endotoxin-induced respiratory failure in pigs

1985 ◽  
Vol 58 (1) ◽  
pp. 274-284 ◽  
Author(s):  
N. C. Olson ◽  
T. T. Brown ◽  
D. L. Anderson
Keyword(s):  
Respiratory Failure ◽  
Phase 1 ◽  
Dynamic Compliance ◽  
Nonsteroidal Antiinflammatory Drugs ◽  
Arachidonic Acid Metabolism ◽  
Antiinflammatory Drugs ◽  
Lung Water ◽  
Pulmonary Response ◽  
Flunixin Meglumine ◽  
Before And After

We studied the porcine pulmonary response to endotoxemia before and after administration of nonsteroidal antiinflammatory drugs (NSAID, i.e., indomethacin or flunixin meglumine) or dexamethasone (DEX). Escherichia coli endotoxin was infused intravenously into anesthetized 10- to 12-wk old pigs for 4.5 h. In endotoxemic pigs, the phase 1 (i.e., 0–2 h) increases in pulmonary arterial pressure, pulmonary vascular resistance (PVR), and alveolar-arterial O2 gradient and the decreases in cardiac index (CI) and lung dynamic compliance (Cdyn) were blocked by NSAID. Thus phase 1 changes were cyclooxygenase dependent. Furthermore, these effects were blocked or greatly attenuated by DEX. During phase 2 of endotoxemia (i.e., 2–4.5 h), the increased PVR and decreased CI and Cdyn were not blocked by NSAID but were attenuated by DEX, suggesting the presence of cyclooxygenase-independent metabolites. Both NSAID and DEX blocked the endotoxin-induced increases in lung water, bronchoalveolar lavage (BAL) neutrophil, and BAL albumin content. The fall in plasma proteins persisted in NSAID but not DEX-treated pigs. We conclude that endotoxemia in the pig causes severe acute respiratory failure largely mediated by cyclooxygenase and possibly lipoxygenase products of arachidonic acid metabolism.

Aspirin Synergistically Potentiates Isoflurane Minimum Alveolar Concentration Reduction Produced by Morphine in the Rat 

1998 ◽  
Vol 89 (6) ◽  
pp. 1489-1494 ◽  
Author(s):  
Ignacio A. Gomez de Segura ◽  
Ana B. Criado ◽  
Martin Santos ◽  
Francisco J. Tendillo
Keyword(s):  
Side Effects ◽  
Minimum Alveolar Concentration ◽  
Synergistic Effects ◽  
Objective Measure ◽  
Nonsteroidal Antiinflammatory Drugs ◽  
Antiinflammatory Drugs ◽  
Before And After ◽  
Male Wistar Rats ◽  
Clinically Significant ◽  
Analgesic Potency

Background The combination of opioids and nonsteroidal antiinflammatory drugs is more analgesic than the summed effect of each drug administered separately. This synergism has been used to obtain analgesia in the postoperative period at doses at which side effects are minimal. The aim of this study is to evaluate the analgesic interaction between aspirin and morphine in the rat during isoflurane anesthesia. The reduction in minimum alveolar concentration of isoflurane (MAC(ISO)) was used as an objective measure of the analgesic potency of individual drugs and their use in combination. Methods Thirty-seven male Wistar rats were anesthetized with isoflurane in oxygen, and the MAC(ISO) was determined before and after the intravenous administration of aspirin and morphine. Rats were administered morphine alone (1, 3, and 10 mg/kg) or morphine (1 and 3 mg/kg) and aspirin (30 mg/kg). The MAC(ISO) was determined from alveolar gas samples at the time of tail clamp. The duration of MAC(ISO) reduction was recorded. Results Aspirin did not have an effect on MAC(ISO), (average, 1.35+/-0.1%), whereas the combination of morphine (1 and 3 mg/kg) and aspirin (30 mg/kg) produced a reduction in the dose of morphine needed to produce the same degree of MAC(ISO) reduction. Actual MAC(ISO+drug) data were as follows: 1 mg/kg morphine, 1.17+/-0.14%; 3 mg/kg morphine, 0.98+/-0.15%; 1 mg/kg morphine plus aspirin, 0.90+/-0.04%; 10 mg/kg morphine, 0.63+/-0.13%; and 3 mg/kg morphine plus aspirin, 0.64+/-0.06%. Conclusions The synergistic effects of aspirin and morphine allow a clinically significant reduction in the requirements of isoflurane and isoflurane plus morphine, and these drug combinations may decrease the side effects associated with the use of single higher, equianalgesic doses of these drugs.

Canine pulmonary response to aerosol histamine: direct versus vagal effects

1977 ◽  
Vol 42 (6) ◽  
pp. 946-952 ◽  
Author(s):  
S. H. Loring ◽  
J. M. Drazen ◽  
R. H. Ingram
Keyword(s):  
Sulfur Hexafluoride ◽  
Dynamic Compliance ◽  
Minor Role ◽  
Small Airways ◽  
Pulmonary Response ◽  
Aerosol Generator ◽  
Vagal Blockade ◽  
Aerosol Exposure ◽  
Before And After ◽  
Dose Dependent

Histamine, a potent bronchoconstrictor, has been shown to produce bronchoconstriction both directly and by a vagal reflex. To define the relative roles of direct and reflex effects, we studied the pulmonary response of dogs exposed to increasing doses of aerosol histamine before and after vagal blockade or vagotomy. In addition, the relative contributions of aerodynamically large and small airways to the overall response were determined by the measurement of pulmonary resistance on sulfur hexafluoride-oxygen and helium-oxygen mixtures. Histamine aerosol caused a similar dose-dependent increase in resistance of aerodynamically large and small airways and fall in dynamic compliance. The dose-response relationships were not consistently altered by either vagal blockade or vagotomy. The following variables were found not to alter the experimental results: anesthesia, type of aerosol generator, control of breathing during aerosol exposure, spontaneous breathing vs. controlled ventilation after aerosol exposure, cold block of vagi vs. vagotomy. We conclude that 1) histamine aerosol in dogs causes a local dose-dependent constriction of bronchial smooth muscle, and 2) the vagus nerve played a relatively minor role in the pulmonary response to aerosol histamine in these experiments.

Dimethylthiourea attenuates endotoxin-induced acute respiratory failure in pigs

1987 ◽  
Vol 63 (6) ◽  
pp. 2426-2432 ◽  
Author(s):  
N. C. Olson ◽  
D. L. Anderson ◽  
M. K. Grizzle
Keyword(s):  
Respiratory Failure ◽  
Acute Respiratory Failure ◽  
Membrane Permeability ◽  
Phase 1 ◽  
Weight Ratio ◽  
Albumin Concentration ◽  
Phase 2 ◽  
Lung Water ◽  
Capillary Membrane ◽  
Alveolar Capillary

We hypothesized that toxic O2 radicals might be important mediators of endotoxin-induced acute respiratory failure in pigs. As a relatively specific scavenger of .OH, we infused dimethylthiourea (DMTU, 1 g/kg) before endotoxemia. Escherichia coli endotoxin (055-B5) was infused intravenously into anesthetized 10- to 14-wk-old pigs at 5 micrograms/kg the 1st h, followed by 2 micrograms.kg-1.h-1 for 3.5 h. During phase 1 (i.e., 0–2 h) and phase 2 (i.e., 2–4.5 h), endotoxin decreased cardiac index (CI) and increased mean pulmonary arterial pressure (Ppa), pulmonary vascular resistance (PVR), alveolar-arterial O2 gradient (AaDo2), and hematocrit (Hct). Endotoxemia also caused leukopenia and increased the postmortem bronchoalveolar lavage fluid (BALF) albumin concentration and wet weight-to-dry weight ratio of bloodless lung. Dimethylthiourea did not significantly modify the phase 1 response. However, during phase 2, DMTU attenuated the endotoxin-induced decrease in CI and increases in Ppa, PVR, Hct, AaDo2, lung water, and BALF albumin concentration. In separate groups of endotoxin- and DMTU + endotoxin-treated pigs, lung microvascular hydrostatic pressure was increased to approximately 16 Torr (by fluid overload) to assess alveolar-capillary membrane permeability. Under these conditions, DMTU markedly attenuated the endotoxin-induced increase in alveolar-capillary membrane permeability. Under these conditions, DMTU markedly attenuated the endotoxin-induced induced increase in alveolar-capillary membrane permeability. We conclude that .OH (and possibly H2O2) significantly contributes to endotoxin-induced lung injury in anesthetized pigs.

scholarly journals Off-label Use of Secukinumab: A Potential Therapeutic Option for SAPHO Syndrome

2021 ◽  
pp. jrheum.211155
Author(s):  
Gang Wang ◽  
Ning Zhuo ◽  
Jingyang Li
Keyword(s):  
Therapeutic Option ◽  
Skin Lesions ◽  
Nonsteroidal Antiinflammatory Drugs ◽  
Substantial Improvement ◽  
Sapho Syndrome ◽  
Whole Body ◽  
Antiinflammatory Drugs ◽  
Before And After ◽  
Body Magnetic Resonance Imaging ◽  
Clinical Conditions

We read the recent article by Wang et al with great interest.1 The authors described a cohort of 4 patients with SAPHO (synovitis, acne, pustulosis, hyperostosis, and osteitis) syndrome who showed substantial improvement in skin lesions, clinical conditions, and whole-body magnetic resonance imaging before and after treatment with secukinumab without concomitant conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), nonsteroidal antiinflammatory drugs (NSAIDs), or other biologics, and suggested a potential benefit of secukinumab in the treatment of SAPHO syndrome. However, there are some details that need further clarification.

scholarly journals CYPC19*17 POLYMORPHISM AS A RISK-FACTOR FOR NSAIDS-INDUCED ULCERS

2016 ◽  
Vol 3 ◽  
pp. 24-30
Author(s):  
Serhiy Tkach ◽  
Lyudmyla Onischuk ◽  
Alexandra Balabanseva
Keyword(s):  
Risk Factors ◽  
Helicobacter Pylori ◽  
Acid Metabolism ◽  
Upper Gastrointestinal Bleeding ◽  
Nonsteroidal Antiinflammatory Drugs ◽  
Arachidonic Acid Metabolism ◽  
Peptic Ulcers ◽  
Antiinflammatory Drugs ◽  
Nsaid Gastropathy ◽  
Upper Gastrointestinal

The new risk-factors for peptic ulcers induced by the use of nonsteroidal antiinflammatory drugs, such as polymorphism of different isoenzymes of cytochrome P450 were considered in the article. The aim of the research was to study different genetic polymorphism of several ferments CYP2C9 and CYP2C19 in inclination to NSAIDS-gastropathies by the way of estimation the risk of appearance of Helicobacter pylori (HP)-positive or Hp-negative NSAIDS- induced peptic ulcers, complicated or not with upper gastrointestinal bleeding. 124 persons were examined (76 men, 48 women in the age of 56,2+/–9,1 years) with Hp-positive or Hp-negative NSAIDS-induced peptic ulcers, that were performed genotyping of isoferments of cytochrome system (CYP2C9, CYP2C19). Based on investigations of 5 different isoenzymes (CYP 2C9*2, CYP 2C9*3, CYP 2C19*2, CYP 2C19*3 and CYP 2C19*17). It was founded that peptic ulcers are strictly associated only with CYP 2C19*17-genotype, possibly due to its involvement in arachidonic acid metabolism and gastroprotection. Thus, polymorphism CYP 2C19*17 can be considered as one of the risk factors for NSAID-gastropathy though the future researches are needed.

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