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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 -
Minerva Anestesiologica May 2014
Topics: Acute Lung Injury; Almitrine; Bronchodilator Agents; Female; Humans; Male; Nitric Oxide; Pulmonary Circulation; Respiratory System Agents
PubMed: 24280828
DOI: No ID Found -
Chest Feb 2000Sleep has well-recognized effects on breathing, including changes in central respiratory control, airways resistance, and muscular contractility, which do not have an... (Review)
Review
Sleep has well-recognized effects on breathing, including changes in central respiratory control, airways resistance, and muscular contractility, which do not have an adverse effect in healthy individuals but may cause problems in patients with COPD. Sleep-related hypoxemia and hypercapnia are well recognized in COPD and are most pronounced in rapid eye movement sleep. However, sleep studies are usually only indicated in patients with COPD when there is a possibility of sleep apnea or when cor pulmonale and/or polycythemia are not explained by the awake PaO(2) level. Management options for patients with sleep-related respiratory failure include general measures such as optimizing therapy of the underlying condition; physiotherapy and prompt treatment of infective exacerbations; supplemental oxygen; pharmacologic treatments such as bronchodilators, particularly ipratropium bromide, theophylline, and almitrine; and noninvasive positive pressure ventilation.
Topics: Adrenergic beta-Agonists; Almitrine; Carbon Dioxide; Cholinergic Antagonists; Humans; Lung Diseases, Obstructive; Oxygen; Positive-Pressure Respiration; Sleep Apnea, Obstructive; Sleep, REM; Theophylline; Ventilation-Perfusion Ratio
PubMed: 10673475
DOI: 10.1378/chest.117.2_suppl.48s -
Respiration Physiology Dec 1988The interaction between almitrine bismesylate, a pharmacological stimulant of peripheral chemoreceptors, and varying levels of oxygen (PO2 50-600 Torr) and carbon...
The interaction between almitrine bismesylate, a pharmacological stimulant of peripheral chemoreceptors, and varying levels of oxygen (PO2 50-600 Torr) and carbon dioxide (PCO2 10-65 Torr) on steady state carotid chemoreceptor discharge was investigated in pentobarbitone-anaesthetised cats. Almitrine was given as constant intravenous (50 micrograms/kg per min for 4 min) and intracarotid infusions (4-16 micrograms/kg per min) at different levels of alveolar PO2 and PCO2. Almitrine always excited discharge. The intracarotid infusions at the lower infusion rate (4-8 micrograms/kg per min) and the i.v. infusions increased the slope of the isoxic response to CO2. This effect could be reversed by raising PO2 to high levels. Higher infusion rates of almitrine (16 micrograms/kg per min) displaced the CO2 response curve upwards but did not increase its slope above that obtained in control conditions at end-tidal PO2 of 50 Torr. However, as these higher infusion rates caused levels of discharge greater than those achieved during control conditions, their effects on control CO2 sensitivity could not be ascertained. Our results suggest that almitrine excites carotid body chemoreceptors by a mechanism similar to that of hypoxia and not like that of carbon dioxide.
Topics: Almitrine; Animals; Carbon Dioxide; Cats; Central Nervous System Stimulants; Chemoreceptor Cells; Female; Hypercapnia; Hypoxia; Male; Oxygen; Piperazines
PubMed: 2906165
DOI: 10.1016/0034-5687(88)90036-9 -
Revue Du Rhumatisme Et Des Maladies... 1990
Review
Topics: Aged; Aged, 80 and over; Almitrine; Diagnosis, Differential; Electromyography; Female; Humans; Male; Middle Aged; Peripheral Nervous System Diseases
PubMed: 2177917
DOI: No ID Found -
The New England Journal of Medicine Dec 2007
Topics: Administration, Inhalation; Almitrine; Extracorporeal Membrane Oxygenation; Humans; Neuromuscular Blocking Agents; Nitric Oxide; Positive-Pressure Respiration; Respiration, Artificial; Respiratory Distress Syndrome; Respiratory System Agents; Tidal Volume
PubMed: 18077819
DOI: 10.1056/NEJMc072900 -
Journal of Applied Physiology... Jul 1989We hypothesized that the temporary blunted ventilatory response to hypoxia seen in chronically hypoxic rats could be related to the increased amount of dopamine found in...
We hypothesized that the temporary blunted ventilatory response to hypoxia seen in chronically hypoxic rats could be related to the increased amount of dopamine found in their carotid bodies. Rats, kept 2-3 wk in 10% O2, showed reduced nonisocapnic ventilatory responses to 21-12% inspiratory O2 fraction compared with control rats. Stimulus-response curves to almitrine, which simulates the action of hypoxia on the carotid body, were also depressed in chronically hypoxic rats. Responses to hypoxia and almitrine were significantly correlated in the two groups of rats. Dopamine depressed ventilation during normoxia, hypoxia, and almitrine stimulation in both groups, an action abolished by the dopamine-2 antagonist domperidone. Domperidone slightly increased responses to hypoxia and almitrine in control rats but had a greater enhancing effect in chronically hypoxic rats, such that there was no longer a difference between the responses of the two groups.
Topics: Almitrine; Animals; Central Nervous System Stimulants; Chronic Disease; Domperidone; Dopamine Antagonists; Hypoxia; Male; Piperazines; Rats; Rats, Inbred Strains; Respiration
PubMed: 2569453
DOI: 10.1152/jappl.1989.67.1.186 -
Presse Medicale (Paris, France : 1983) Oct 1984Animal studies performed in various species have shown that the compound induces different effects depending on dosage: At high doses, almitrine bismesylate specifically... (Review)
Review
Animal studies performed in various species have shown that the compound induces different effects depending on dosage: At high doses, almitrine bismesylate specifically stimulates the aortic and carotid chemoreceptors, with subsequent increase in ventilation and improvement in arterial blood gases. At low doses, almitrine bismesylate increases arterial oxygen pressure (PaO2) in the anaesthetized dog without any ventilatory change. The only effect occurring simultaneously with the increase in PaO2 is transient vasoconstriction of the pulmonary vascular bed. Dissociation between PaO2 and ventilation has also been observed in clinical trials performed in patients with chronic bronchitis and has been attributed to a normalization of ventilation/perfusion (VA/Q) ratios. Animal pharmacological studies were undertaken in order to elucidate the mechanism underlying the improvement of the VA/Q ratios by almitrine bismesylate. Results suggested that both redistribution of ventilation and perfusion concurred to improve alveolar gas and pulmonary circulation matching and thus alveolar blood-gas exchanges.
Topics: Administration, Oral; Almitrine; Animals; Central Nervous System Stimulants; Chemoreceptor Cells; Hemodynamics; Humans; Injections, Intravenous; Pentobarbital; Piperazines; Time Factors; Ventilation-Perfusion Ratio
PubMed: 6149533
DOI: No ID Found -
The European Respiratory Journal Jan 1989To better define the dose-effect relationship and the pharmacokinetics of almitrine, sixteen stable hypoxaemic COPD patients received random single oral administrations... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
To better define the dose-effect relationship and the pharmacokinetics of almitrine, sixteen stable hypoxaemic COPD patients received random single oral administrations of almitrine bismesylate 50, 100 and 150 mg or placebo at two-week intervals in a double-blind manner. Resting ventilation, arterial blood gases and plasma almitrine levels were measured. No significant changes were seen after placebo administration. Almitrine 50 and 100 mg caused a significant dose-related improvement in arterial oxygen tension (PaO2) in thirteen of the sixteen patients. Almitrine 150 mg caused little if any additional PaO2 increment. PaO2 returned to near basal values after 24 h. Two patients responded to almitrine 100 and 150 mg only, whereas one patient did not respond at all. Mean PaO2 increases in the sixteen patients were 0.9 kPa (7 mmHg), 1.5 kPa (11 mmHg) and 1.6 kPa (12 mmHg) 3 h after 50, 100 and 150 mg, respectively. A significant mean 0.9 kPa (7 mmHg) decrease in arterial carbon dioxide tension (PaCO2) and a l.min-1 increase in ventilation were observed after almitrine 150 mg. Mean maximum almitrine plasma concentration and area under the curve correlated linearly with dose. The relationship between mean PaO2 improvement and mean almitrine plasma level was curvilinear with a flattening of the curve over plasma levels of 150 ng.ml-1. Almitrine plasma half-life was found to be 116-140 h.
Topics: Aged; Almitrine; Carbon Dioxide; Dose-Response Relationship, Drug; Half-Life; Humans; Hypoxia; Lung Diseases, Obstructive; Male; Middle Aged; Oxygen; Piperazines
PubMed: 2495983
DOI: No ID Found -
Journal of Applied Physiology... Aug 1987Almitrine increases ventilation by stimulating the peripheral arterial chemoreceptors. This study assessed the effects of acute and chronic almitrine treatments on the...
Almitrine increases ventilation by stimulating the peripheral arterial chemoreceptors. This study assessed the effects of acute and chronic almitrine treatments on the dopamine (DA) and norepinephrine (NE) contents and utilization rates in the rat carotid body. Almitrine (5 mg/kg ip) caused a 34% reduction in DA content after 30 min. Extending the almitrine treatment for 15 days (one daily ip injection) produced a further progressive diminution in DA stores (-55%; P less than 0.01). The utilization rate of DA measured after inhibiting catecholamine biosynthesis by alpha-methyl-p-tyrosine was strongly reduced by almitrine (-98% after 15 days; P less than 0.01). The effects of almitrine were dose dependent. The noradrenergic activity was much less altered by the drug. The data showed that almitrine can modify the dynamics of DA in rat carotid body producing a decrease in both content and utilization rate.
Topics: Almitrine; Animals; Carotid Body; Dopamine; Dopamine Antagonists; Dose-Response Relationship, Drug; Male; Norepinephrine; Piperazines; Rats; Rats, Inbred Strains; Respiration
PubMed: 3654437
DOI: 10.1152/jappl.1987.63.2.746