Interactions between hypoxic and almitrine-induced vasoconstriction in the rat lung

1992 ◽  
Vol 82 (3) ◽  
pp. 265-272 ◽  
Author(s):  
P. C. Russell ◽  
C. J. Emery ◽  
J. Nicholl ◽  
G. R. Barer ◽  
P. Howard
Keyword(s):  
Chronic Obstructive ◽  
Response Curves ◽  
Stimulus Response ◽  
Pulmonary Vasoconstriction ◽  
Hypoxic Vasoconstriction ◽  
Small Doses ◽  
Sigmoid Curve ◽  
Obstructive Airways Disease ◽  
High Doses ◽  
Parallel Fashion

1. To test whether almitrine might improve the arterial partial pressure of O2 in patients with chronic obstructive airways disease by improvement of ventilation-perfusion matching, we looked at the interaction between hypoxic and almitrine-induced vasoconstriction in isolated rat lungs perfused with blood at constant flow. Increases in pressure represented increases in resistance. 2. Almitrine, given in increasing doses between challenges with 2% O2, enhanced hypoxic vasoconstriction at low doses but attenuated it at high doses. 3. Stimulus-response curves to hypoxia of increasing severity gave a sigmoid curve. 4. Almitrine solvent caused small changes in pulmonary artery pressure and shifted the stimulus-response curve slightly in a parallel fashion. 5. Small doses of almitrine enhanced the action of mild to moderate hypoxia, medium doses attenuated moderately severe hypoxia, whereas high doses depressed vasoconstriction due to all degrees of hypoxia. 6. These effects of almitrine on hypoxic vasoconstriction were compared with the effect of solvent by analysis of variance; the results substantiated significant enhancement of hypoxia by small doses and attenuation by large doses. 7. In patients, if similar effects apply, small doses of almitrine would assist ventilation-perfusion matching, but large doses might worsen it. 8. Almitrine-induced vasoconstriction was attenuated by a fall in perfusate temperature in a similar manner to hypoxic vasoconstriction. It was also attenuated by three drugs, chlorpheniramine, propanolol and diethylcarbamazine, all of which also decrease hypoxic vasoconstriction. The similarity between hypoxic and almitrine-induced pulmonary vasoconstriction is further confirmed.

Effects of indomethacin on estradiol-induced attenuation of hypoxic vasoconstriction in lamb lungs

1986 ◽  
Vol 61 (6) ◽  
pp. 2116-2121 ◽  
Author(s):  
J. B. Gordon ◽  
R. C. Wetzel ◽  
M. L. McGeady ◽  
N. F. Adkinson ◽  
J. T. Sylvester
Keyword(s):  
Steady State ◽  
Pulmonary Arterial Pressure ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Response Relationship ◽  
Stimulus Response ◽  
Pulmonary Vasoconstriction ◽  
Pulmonary Vasodilator ◽  
Hypoxic Vasoconstriction ◽  
Pulmonary Arterial ◽  
Isolated Lungs

To determine whether cyclooxygenase products mediated the attenuation of hypoxic pulmonary vasoconstriction induced by estradiol, we measured pulmonary arterial pressure at a flow of 50 ml X min-1 X kg-1 (Ppa50) during steady-state exposures to inspired O2 tensions (PIO2) between 0 and 200 Torr in isolated lungs of juvenile ewes. Intramuscular estradiol (10 mg) 44–60 h before study significantly decreased perfusate concentrations of 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha), the stable metabolite of the pulmonary vasodilator, prostacyclin, but did not significantly affect the stimulus-response relationship between PIO2 and Ppa50. Estradiol (20 mg) 3–5 days before study increased 6-keto-PGF1 alpha concentrations and decreased Ppa50 at PIO2 of 10, 30, and 50 Torr. Indomethacin added to the perfusate of these lungs reduced 6-keto-PGF1 alpha to undetectable levels and altered the estradiol-induced attenuation, increasing Ppa50 at PIO2 of 10 and 30 Torr, but decreasing Ppa50 at PIO2 of 200 Torr. Despite these effects, Ppa50 remained lower than the values measured in lungs not treated with estradiol. These results suggest that the estradiol-induced attenuation of the hypoxic stimulus-response relationship was mediated only in part by cyclooxygenase products, the net effects of which were vasodilation at PIO2 of 10 and 30 Torr, but vasoconstriction at PIO2 of 200 Torr.

Stimulus-response curves for hypoxic pulmonary vasoconstriction in piglets

1992 ◽  
Vol 26 (10) ◽  
pp. 944-949 ◽  
Author(s):  
D. D. Canniere ◽  
C. Stefanidis ◽  
R. Hallemans ◽  
M. Delcroix ◽  
S. Brimioulle ◽  
...  
Keyword(s):  
Hypoxic Pulmonary Vasoconstriction ◽  
Response Curves ◽  
Stimulus Response ◽  
Pulmonary Vasoconstriction

scholarly journals Current knowledge about the etiopathogenesis and therapy options for COVID-19

2020 ◽  
Vol 49 (3) ◽  
pp. 43-54
Author(s):  
Srđan Pešić ◽  
Hristina Jovanović ◽  
Hristina Trajković
Keyword(s):  
Vitamin C ◽  
Current Knowledge ◽  
Inflammatory Diseases ◽  
World Health ◽  
Chronic Obstructive ◽  
Biological Drugs ◽  
Multisystem Disease ◽  
The World ◽  
Small Doses ◽  
High Doses

Currently, over 35 million people in the world are infected with the COVID-19 and over a million have died. The pandemic character of the disease has imposed dynamic research both in the field of clarification of the etiopathogenetic mechanisms of the disease and in the field of possible therapy. The amount of scientific knowledge has increased dozens of times in the last nine months, but we are still not even close to define an effective and safe therapy. The knowledge that COVID-19 is not only a respiratory but also a multisystem disease, which affects almost all organs, gave us opportunities for therapeutic adjustments. Strong oxidative stress, silent chronic hypoxia, increased coagulability, and increased platelet aggregation are just some of the mechanisms in the development of the disease. Cardiovascular consequences and vascular endothelial dysfunction are thought to be mainly responsible for death with a dangerous cytokine storm and acute respiratory distress syndrome. Having all this in mind in the therapeutic sense, it is proposed to use antibiotics, high doses of vitamin C, blood transfusion, immunoglobulin, interferon, anti-IL-6 antibodies, small doses of Dexamethasone or other corticosteroids, specific antiviral drugs such as favipiravir and remdesivir. The use of chloroquine is excluded from the therapeutic protocols of the World Health Organization and the Centers for Disease Control and Prevention (United States of America). For preventive and supportive purposes, high doses of vitamin D, vitamin C, zinc, probiotics, Alpha-lipoic acid, and other supplements are recommended. The use of anti-inflammatory, analgo-antipyretics drugs is considered justified, as well as the use of small doses of acetylsalicylic acid. Over 70 other drugs are currently being tested in over 400 clinical studies. In patients who already use corticosteroids by inhalation or intranasally due to asthma, chronic obstructive pulmonary disease, allergic rhinitis, or biological drugs due to immunomodulatory inflammatory diseases, this therapy should not be changed and it is not a prerequisite condition for more severe forms of the disease. The specifics of the infection in special populations such as children or pregnant women must also be taken into consideration.

Stimulus-response curve of hypoxic pulmonary vasoconstriction in intact dogs: effects of ASA

1994 ◽  
Vol 77 (1) ◽  
pp. 476-480 ◽  
Author(s):  
S. Brimioulle ◽  
P. Lejeune ◽  
J. L. Vachiery ◽  
M. Delcroix ◽  
R. Hallemans ◽  
...  
Keyword(s):  
Response Curve ◽  
Intact Animal ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Severe Hypoxia ◽  
Response Curves ◽  
Cyclooxygenase Inhibition ◽  
Stimulus Response ◽  
Pulmonary Vasoconstriction ◽  
The Difference ◽  
Isolated Lungs

Hypoxic pulmonary vasoconstriction (HPV) has been reported to decrease during severe hypoxia in isolated lungs, but it remains unknown whether this decrease occurs in the intact animal and how it is affected by cyclooxygenase inhibition. We investigated the HPV stimulus-response relationship in eight pentobarbital sodium-anesthetized intact dogs with a naturally occurring response to hypoxia (“responders”). The pulmonary arterial minus wedge pressure difference (Ppa-Ppw) was measured at 11 inspired O2 fraction (FIO2) values between 0.40 and 0.04 while ventilation, cardiac output, and acid-base status were kept constant. Ppa-Ppw increased by 8 +/- 1 mmHg between FIO2 of 0.40 and 0.10 (alveolar PO2 of approximately 40 Torr) and decreased by 3 +/- 1 mmHg between FIO2 of 0.10 and 0.04. To assess the effects of cyclooxygenase inhibition, similar stimulus-response curves were obtained after administration of 20 mg/kg of acetylsalicylic acid (ASA) in 16 more dogs selected as either nonresponders or responders to hypoxia. ASA restored HPV in nonresponders and enhanced HPV in responders, with the difference between Ppa-Ppw at FIO2 of 0.10 and 0.40 increasing from 1 +/- 1 to 8 +/- 1 mmHg (P < 0.001) and from 7 +/- 1 to 10 +/- 1 mmHg (P < 0.05), respectively. In both groups, the shape of the stimulus-response curve after ASA was comparable to that of spontaneous HPV, with a maximum at FIO2 of 0.10 and a significant decrease at lower FIO2. We conclude that severe hypoxia attenuates HPV in the intact animal and that ASA restores or enhances HPV by affecting the magnitude of the hypoxic response and not the sensitivity to hypoxia.

Lauric Acid-Induced Thrombocytopenia and Thrombosis in Rabbits

1967 ◽  
Vol 18 (01/02) ◽  
pp. 057-065 ◽  
Author(s):  
G Zbinden
Keyword(s):  
Acid Solution ◽  
Intravenous Injection ◽  
Lauric Acid ◽  
Repeated Administration ◽  
Intravenous Dose ◽  
Acid Injection ◽  
Small Doses ◽  
High Doses

SummaryIntravenous injection of 0.5% lauric acid solution into rabbits caused moderate to marked thrombocytopenia. With small doses (2.5 mg/kg) this thrombocyte decrease was reversible and microscopically demonstrable thrombosis in the lungs was only seen or suspected in a small number of rabbits 10 to 30 min after lauric acid injection. High doses were followed by partly reversible thrombocytopenia and by moderate to marked, sometimes lethal, thrombosis in the lungs still demonstrable 24 hrs after injection. Repeated administration of small doses of lauric acid did not lead to a depletion of the circulating thrombocytes. Thrombocytopenic response, however, appeared to be less pronounced after the second and subsequent injections. Studies with Cr51-labeled platelets indicate that during the reversible thrombocytopenia following a small intravenous dose of lauric acid platelets are retained in various organs, particularly the lungs.

scholarly journals Influence of N-acetylcysteine on chronic bronchitis or COPD exacerbations: a meta-analysis

2015 ◽  
Vol 24 (137) ◽  
pp. 451-461 ◽  
Author(s):  
Mario Cazzola ◽  
Luigino Calzetta ◽  
Clive Page ◽  
Josè Jardim ◽  
Alexander G. Chuchalin ◽  
...  
Keyword(s):  
Relative Risk ◽  
Airway Obstruction ◽  
Chronic Bronchitis ◽  
Meta Analysis ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Regular Treatment ◽  
Copd Exacerbations ◽  
Copd Patients ◽  
High Doses

In order to clarify the possible role of N-acetylcysteine (NAC) in the treatment of patients with chronic bronchitis and chronic obstructive pulmonary disease (COPD), we have carried out a meta-analysis testing the available evidence that NAC treatment may be effective in preventing exacerbations of chronic bronchitis or COPD and evaluating whether there is a substantial difference between the responses induced by low (≤600 mg per day) and high (>600 mg per day) doses of NAC.The results of the present meta-analysis (13 studies, 4155 COPD patients, NAC n=1933; placebo or controls n=2222) showed that patients treated with NAC had significantly and consistently fewer exacerbations of chronic bronchitis or COPD (relative risk 0.75, 95% CI 0.66–0.84; p<0.01), although this protective effect was more apparent in patients without evidence of airway obstruction. However, high doses of NAC were also effective in patients suffering from COPD diagnosed using spirometric criteria (relative risk 0.75, 95% CI 0.68–0.82; p=0.04). NAC was well tolerated and the risk of adverse reactions was not dose-dependent (low doses relative risk 0.93, 95% CI 0.89–0.97; p=0.40; high doses relative risk 1.11, 95% CI 0.89–1.39; p=0.58).The strong signal that comes from this meta-analysis leads us to state that if a patient suffering from chronic bronchitis presents a documented airway obstruction, NAC should be administered at a dose of ≥1200 mg per day to prevent exacerbations, while if a patient suffers from chronic bronchitis, but is without airway obstruction, a regular treatment of 600 mg per day seems to be sufficient.

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