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Chest Nov 2020
Topics: Aged; Almitrine; Betacoronavirus; Blood Gas Analysis; COVID-19; Coronavirus Infections; Extracorporeal Membrane Oxygenation; Female; Humans; Hypoxia; Male; Middle Aged; Oxygen; Oxygen Inhalation Therapy; Pandemics; Partial Pressure; Patient Positioning; Pneumonia, Viral; Positive-Pressure Respiration; Prone Position; Respiration, Artificial; Respiratory Distress Syndrome; Respiratory System Agents; Retrospective Studies; SARS-CoV-2; Treatment Outcome
PubMed: 32512007
DOI: 10.1016/j.chest.2020.05.573 -
The European Respiratory Journal May 1994The aim of this double-blind, placebo-controlled study was to determine whether acute administration of almitrine enhances hypoxic pulmonary vasoconstriction in patients... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
The aim of this double-blind, placebo-controlled study was to determine whether acute administration of almitrine enhances hypoxic pulmonary vasoconstriction in patients with chronic obstructive pulmonary disease (COPD). Haemodynamics and blood gases were studied at various inspiratory fractional concentrations of oxygen (FIO2): 0.15, 0.21, 0.30 and 1.0, randomly administered for 20 min periods under constant infusion of either placebo or almitrine (8 micrograms.kg-1.min-1) in 20 patients with COPD. The almitrine group exhibited a significant increase in mean pulmonary artery pressure, pulmonary vascular resistance and arterial oxygen tension (PaO2) at FIO2 0.15, 0.21 and 0.30. During hypoxia, the increase in mean pulmonary pressure and pulmonary vascular resistance was three times greater in the almitrine group than the placebo group. No significant difference in cardiac output and systemic haemodynamics was found. These results suggest that almitrine at the dose used, enhances pulmonary vasoconstriction in COPD patients.
Topics: Almitrine; Carbon Dioxide; Double-Blind Method; Female; Hemodynamics; Humans; Lung Diseases, Obstructive; Male; Middle Aged; Oxygen; Oxygen Consumption; Pulmonary Circulation; Vasomotor System
PubMed: 8050541
DOI: No ID Found -
Thorax Mar 1983The respiratory effects of intravenously infused almitrine were evaluated in healthy volunteers. In the dose range 0.25-1.0 mg/kg/hour it caused large and dose-dependent...
The respiratory effects of intravenously infused almitrine were evaluated in healthy volunteers. In the dose range 0.25-1.0 mg/kg/hour it caused large and dose-dependent increases in hypoxic chemosensitivity, which were longlasting and more persistent than the drug's retention in the plasma. Increases in sensitivity to hypercapnia were much less and were detected only when the plasma almitrine exceeded 200 ng/ml. Small increases in resting ventilation and metabolic rate with a decrease in mixed venous carbon dioxide tension occurred only at the highest infusion rate. The findings accord with an action of almitrine in the peripheral chemoreceptors, which may be of therapeutic value in managing some cases of respiratory failure.
Topics: Adult; Almitrine; Central Nervous System Stimulants; Dose-Response Relationship, Drug; Double-Blind Method; Female; Humans; Infusions, Parenteral; Male; Piperazines; Respiration; Respiratory Function Tests
PubMed: 6134350
DOI: 10.1136/thx.38.3.200 -
The Tohoku Journal of Experimental... Feb 1989The purpose of this study is to test how almitrine bismesylate (Alm) affects the function of pulmonary vasculature during normoxic ventilation, and whether low doses of...
The purpose of this study is to test how almitrine bismesylate (Alm) affects the function of pulmonary vasculature during normoxic ventilation, and whether low doses of Alm not causing detectable vasoconstriction during normoxic ventilation potentiate hypoxic pulmonary vasoconstriction (HPVC). Isolated Wistar male rat lungs were perfused with homologous blood at constant flow, and venous and ventilatory pressure. In the first experiment, after equilibration, dose-response curves to Alm (from 0 to 1000 ng/ml, n = 10) were measured under the ventilation with normoxic gas mixture (21% O2, 5% CO2, 74% N2). It was found that Alm causes a dose-dependent pulmonary vasoconstriction. In the second experiment, low doses of Alm (125 mg/ml) or diluent of Alm (malic acid) was injected to the blood reservoir. This doses of Alm did not cause significant vasoconstriction during normoxic gas ventilation compared with malic acid. After stabilization of pulmonary arterial pressure, the lungs were exposed to three cycles of normoxia (10 min) and hypoxia (10 min) through ventilation with gas containing 21% or 2% O2 and 5% CO2. It was observed that low doses of Alm significantly reduce HPVC (p less than 0.05) on the later periods of the first and the second hypoxic challenges. However, no significant difference was revealed among two groups in the third hypoxic challenge. Directly measured blood Alm concentration was significantly lower in the third challenge than in the first challenge. Responses to angiotensin II were not decreased by Alm. In conclusion, high doses of Alm constrict pulmonary vasculature dose-dependently, and low doses of the drug not causing vasoconstriction during normoxia reduce HPVC in rat.
Topics: Almitrine; Animals; Body Weight; Hemodynamics; In Vitro Techniques; Lung; Male; Oxygen; Piperazines; Rats; Rats, Inbred Strains; Vasoconstriction
PubMed: 2711381
DOI: 10.1620/tjem.157.119 -
Biochimica Et Biophysica Acta Mar 1995Autonomous cell growth may result from interactions of cellular growth factors with their receptors leading to the establishment of external or internal autocrine loops...
Autonomous cell growth may result from interactions of cellular growth factors with their receptors leading to the establishment of external or internal autocrine loops which can induce tumor formation. Tumor progression above a small volume also requires an increase in blood supply. This is achieved by the release from the tumor of angiogenic growth factors which diffuse toward preexisting capillaries. The search for compounds interfering with growth factors and their receptors represents a field of investigation of increasing importance. In this report we show that almitrine interferes with the binding of basic fibroblast growth factor and vasculotropin/vascular endothelial growth factor to their receptors present on vascular endothelial cells, smooth muscle cells or retinal pigment epithelium. This molecule inhibits reversibly serum and basic growth factors stimulated cell growth and motility without affecting epidermal growth factor-stimulated proliferation.
Topics: Almitrine; Animals; Aorta; Cattle; Cells, Cultured; Endothelium, Vascular; Fibroblast Growth Factor 2; Growth Substances; Muscle, Smooth, Vascular; Pigment Epithelium of Eye; Receptors, Cytokine; Receptors, Fibroblast Growth Factor; Receptors, Growth Factor; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors
PubMed: 7696345
DOI: 10.1016/0167-4889(94)00215-z -
Experimental Physiology Jan 1992The contribution of almitrine bismesylate to the occurrence and pattern of augmented breaths was studied in fifteen spontaneously breathing, anaesthetized cats....
The contribution of almitrine bismesylate to the occurrence and pattern of augmented breaths was studied in fifteen spontaneously breathing, anaesthetized cats. Breathing was via a tracheostomy, while the laryngeal resistance to airflow was measured with the larynx isolated in situ. Almitrine bismesylate at a dose of 0.5 mg kg-1 of body weight was injected intravenously in the intact animals and following bilateral vagotomy which spared the right recurrent laryngeal nerve. Almitrine injected intravenously elicited augmented breaths within the first 45 s in thirteen cats and within 1 min in the remaining two cats. During augmented breaths inspiratory and expiratory airflows rose, the mean increases being 385.2 and 159.6% respectively above the controls (P less than 0.01). The inspiratory laryngeal resistance declined to 77.7% of the control (P less than 0.01) and expiratory laryngeal resistance increased by 95.4% above the control level (P less than 0.01). The inspiratory and expiratory times were prolonged by 56 and 58% compared with baseline breathing. Following the augmented breaths the respiratory airflows exceeded baseline values, the respiratory timing was slightly reduced, and the inspiratory laryngeal resistance was significantly lowered below the control level (P less than 0.01). The expiratory laryngeal resistance showed the same trend without statistical significance. Bilateral vagotomy abolished the occurrence of augmented breaths following almitrine injection.
Topics: Airway Resistance; Almitrine; Animals; Cats; Chemoreceptor Cells; Female; Larynx; Male; Respiration; Respiratory Mechanics; Vagotomy; Vagus Nerve
PubMed: 1543580
DOI: 10.1113/expphysiol.1992.sp003565 -
Thorax Apr 1989A double blind prospective study of the effect of almitrine bismesylate and placebo on peripheral-nerve function was carried out in 12 patients with chronic bronchitis... (Clinical Trial)
Clinical Trial
A double blind prospective study of the effect of almitrine bismesylate and placebo on peripheral-nerve function was carried out in 12 patients with chronic bronchitis and arterial hypoxaemia (mean (SD) FEV1% predicted 38 (16), arterial oxygen tension (PaO2) 7.56 (0.76) kPa). Of the seven patients who took placebo, none developed symptoms or signs of peripheral neuropathy. One patient who had abnormal lower limb sensory nerve conduction initially showed improvement of sensory conduction but deterioration in motor conduction during the 12 month study period. Two further patients developed some slowing of motor conduction velocities in their right lateral popliteal nerve. Five patients received almitrine and all showed an improvement in PaO2 (mean from 7.0 to 7.9 kPa). None had symptoms or signs of peripheral neuropathy on entry to the study; one patient had evidence of impaired nerve conduction on electrophysiological testing. Three patients developed symptoms and signs of peripheral neuropathy during the 12 months of the study and a fourth developed peripheral neuropathy at 18 months, having continued to receive almitrine. Studies of nerve physiology showed abnormalities in the lower limbs of all four patients. Recovery was poor, possibly because of the long half life of almitrine. The studies suggest that almitrine may precipitate peripheral neuropathy in patients with chronic obstructive pulmonary disease. Patients should be warned of this potential complication so that the drug can be stopped as soon as symptoms develop.
Topics: Aged; Almitrine; Bronchitis; Chronic Disease; Double-Blind Method; Female; Humans; Male; Middle Aged; Peripheral Nervous System Diseases; Piperazines; Prospective Studies
PubMed: 2548299
DOI: 10.1136/thx.44.4.292 -
Quarterly Journal of Experimental... Oct 1985It has been suggested that avian vagal intrapulmonary CO2-sensitive receptors (i.p.c.) may be capable of monitoring the rate and extent of CO2 wash-out from the lung...
It has been suggested that avian vagal intrapulmonary CO2-sensitive receptors (i.p.c.) may be capable of monitoring the rate and extent of CO2 wash-out from the lung during spontaneous breathing. The purpose of this study was to record i.p.c. discharge activity in spontaneously breathing domestic fowl when minute volume (VI) was elevated from resting levels. This was accomplished by administration of almitrine (2 mg X kg-1 I.V.), a respiratory stimulant drug that has been shown to have a specific long-lasting stimulatory action on carotid body chemoreceptors. Unanaesthetized decerebrate fowl were tracheotomized and single-unit activity was recorded from sixteen vagal i.p.c. When ventilation was elevated 2.2-fold by almitrine (initially by increases in tidal volume (VT)) i.p.c. discharge was increased in both inspiration and expiration, and the delay period before the onset of i.p.c. discharge in inspiration was markedly shortened. Within 5-10 min after the administration of almitrine, the breathing pattern changed to one of rapid, shallow breathing, although the 2.2-fold elevation of the rate of gas flow through the parabronchi (V) and mean inspiratory flow rate (VT/TI) were maintained. The i.p.c. continued to fire phasically, with peaks of discharge in both inspiration and expiration, though there were fewer spikes per breath and mean inspiratory peak discharge rate returned to control (eupnoeic) levels. It is concluded that i.p.c. discharge is increased when VI is elevated in the spontaneously breathing fowl and that the pattern of discharge is dependent on the pattern of breathing. I.p.c. show high dynamic sensitivity to changes in the PCO2 of their microenvironment and it is possible to explain the changes in discharge pattern observed in terms of the PCO2 changes in the lungs and air sacs. These results support proposals that the pattern of breathing is to some extent dependent upon the intensity and timing of i.p.c. activity.
Topics: Almitrine; Animals; Carbon Dioxide; Carotid Body; Chemoreceptor Cells; Chickens; Electrophysiology; Female; Hyperventilation; Lung; Piperazines; Respiration; Tidal Volume
PubMed: 3936110
DOI: 10.1113/expphysiol.1985.sp002937 -
Respiration; International Review of... 2003
Topics: Almitrine; Humans; Oxygen; Respiration; Respiratory Muscles; Respiratory System Agents
PubMed: 14665766
DOI: 10.1159/000074197 -
Anesthesiology Jun 1997Enhancement of hypoxic pulmonary vasoconstriction (HPV) in nonventilated lung areas by almitrine increases the respiratory response to inhaled nitric oxide (NO) in... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
BACKGROUND
Enhancement of hypoxic pulmonary vasoconstriction (HPV) in nonventilated lung areas by almitrine increases the respiratory response to inhaled nitric oxide (NO) in patients with acute respiratory distress syndrome (ARDS). Therefore the authors hypothesized that inhibition of HPV in nonventilated lung areas decreases the respiratory effects of NO.
METHODS
Eleven patients with severe ARDS treated by venovenous extracorporeal lung assist were studied. Patients' lungs were ventilated at a fraction of inspired oxygen (F[I(O2)]) of 1.0. By varying extracorporeal blood flow, mixed venous oxygen tension (P[O2]; partial oxygen pressure in mixed venous blood [PV(O2)]) was adjusted randomly to four levels (means, 47, 54, 64 and 84 mmHg). Extracorporeal gas flow was adjusted to prevent changes in mixed venous carbon dioxide tension [PV(CO2)]). Hemodynamic and gas exchange variables were measured at each level before, during, and after 15 ppm NO.
RESULTS
Increasing PV(O2) from 47 to 84 mmHg resulted in a progressive decrease in lung perfusion pressure (PAP-PAWP; P < 0.05) and pulmnonary vascular resistance index (PVRI; P < 0.05) and in an increase in intrapulmonary shunt (Q[S]/Q[T]; P < 0.05). PV(CO2) and cardiac index did not change. Whereas the NO-induced reduction in PAP-PAWP was smaller at high PV(O2), NO-induced decrease in Q(S)/Q(T) was independent of baseline PV(O2). In response to NO, arterial P(O2) increased more and arterial oxygen saturation increased less at high compared with low PV(O2).
CONCLUSION
In patients with ARDS, HPV in nonventilated lung areas modifies the hemodynamic and respiratory response to NO. The stronger the HPV in nonventilated lung areas the more pronounced is the NO-induced decrease in PAP-PAWP. In contrast, the NO-induced decrease in Q(S)/Q(T) is independent of PV(O2) over a wide range of PV(O2) levels. The effect of NO on the arterial oxygen tension varies with the level of PV(O2) by virtue of its location on the oxygen dissociation curve.
Topics: Administration, Inhalation; Adult; Extracorporeal Membrane Oxygenation; Female; Hemodynamics; Humans; Hypoxia; Lung; Male; Middle Aged; Nitric Oxide; Oxygen; Perfusion; Pulmonary Circulation; Pulmonary Gas Exchange; Respiratory Distress Syndrome; Vasoconstriction
PubMed: 9197293
DOI: 10.1097/00000542-199706000-00005