Almitrine: A respiratory stimulant that enhances respiration by acting as an agonist of peripheral chemoreceptors located on the carotid bodies. The drug increases arterial oxygen tension while decreasing arterial carbon dioxide tension in patients with chronic obstructive pulmonary disease. It may also prove useful in the treatment of nocturnal oxygen desaturation without impairing the quality of sleep.Respiratory System Agents: Drugs used for their effects on the respiratory system.Pulmonary Heart Disease: Hypertrophy and dilation of the RIGHT VENTRICLE of the heart that is caused by PULMONARY HYPERTENSION. This condition is often associated with pulmonary parenchymal or vascular diseases, such as CHRONIC OBSTRUCTIVE PULMONARY DISEASE and PULMONARY EMBOLISM.Doxapram: A central respiratory stimulant with a brief duration of action. (From Martindale, The Extra Pharmocopoeia, 30th ed, p1225)Levorphanol: A narcotic analgesic that may be habit-forming. It is nearly as effective orally as by injection.Lung Diseases, Obstructive: Any disorder marked by obstruction of conducting airways of the lung. AIRWAY OBSTRUCTION may be acute, chronic, intermittent, or persistent.Vasoconstriction: The physiological narrowing of BLOOD VESSELS by contraction of the VASCULAR SMOOTH MUSCLE.Anoxia: Relatively complete absence of oxygen in one or more tissues.Ventilation-Perfusion Ratio: The ratio of alveolar ventilation to simultaneous alveolar capillary blood flow in any part of the lung. (Stedman, 25th ed)Marketing: Activity involved in transfer of goods from producer to consumer or in the exchange of services.Research Report: Detailed account or statement or formal record of data resulting from empirical inquiry.Dextroamphetamine: The d-form of AMPHETAMINE. It is a central nervous system stimulant and a sympathomimetic. It has also been used in the treatment of narcolepsy and of attention deficit disorders and hyperactivity in children. Dextroamphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulating release of monamines, and inhibiting monoamine oxidase. It is also a drug of abuse and a psychotomimetic.Foundations: Organizations established by endowments with provision for future maintenance.Dietetics: The application of nutritional principles to regulation of the diet and feeding persons or groups of persons.Acidosis, Lactic: Acidosis caused by accumulation of lactic acid more rapidly than it can be metabolized. It may occur spontaneously or in association with diseases such as DIABETES MELLITUS; LEUKEMIA; or LIVER FAILURE.Respiratory Distress Syndrome, Adult: A syndrome characterized by progressive life-threatening RESPIRATORY INSUFFICIENCY in the absence of known LUNG DISEASES, usually following a systemic insult such as surgery or major TRAUMA.Acute Lung Injury: A condition of lung damage that is characterized by bilateral pulmonary infiltrates (PULMONARY EDEMA) rich in NEUTROPHILS, and in the absence of clinical HEART FAILURE. This can represent a spectrum of pulmonary lesions, endothelial and epithelial, due to numerous factors (physical, chemical, or biological).Regional Blood Flow: The flow of BLOOD through or around an organ or region of the body.Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells, synthesized from ARGININE by NITRIC OXIDE SYNTHASE. Nitric oxide is one of the ENDOTHELIUM-DEPENDENT RELAXING FACTORS released by the vascular endothelium and mediates VASODILATION. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic GUANYLATE CYCLASE and thus elevates intracellular levels of CYCLIC GMP.Hepatitis, Infectious Canine: A contagious disease caused by canine adenovirus (ADENOVIRUSES, CANINE) infecting the LIVER, the EYE, the KIDNEY, and other organs in dogs, other canids, and bears. Symptoms include FEVER; EDEMA; VOMITING; and DIARRHEA.Nitric Oxide Synthase: An NADPH-dependent enzyme that catalyzes the conversion of L-ARGININE and OXYGEN to produce CITRULLINE and NITRIC OXIDE.Sepsis: Systemic inflammatory response syndrome with a proven or suspected infectious etiology. When sepsis is associated with organ dysfunction distant from the site of infection, it is called severe sepsis. When sepsis is accompanied by HYPOTENSION despite adequate fluid infusion, it is called SEPTIC SHOCK.Dog Diseases: Diseases of the domestic dog (Canis familiaris). This term does not include diseases of wild dogs, WOLVES; FOXES; and other Canidae for which the heading CARNIVORA is used.Free Radicals: Highly reactive molecules with an unsatisfied electron valence pair. Free radicals are produced in both normal and pathological processes. They are proven or suspected agents of tissue damage in a wide variety of circumstances including radiation, damage from environment chemicals, and aging. Natural and pharmacological prevention of free radical damage is being actively investigated.Nitric Oxide Synthase Type II: A CALCIUM-independent subtype of nitric oxide synthase that may play a role in immune function. It is an inducible enzyme whose expression is transcriptionally regulated by a variety of CYTOKINES.Metabolomics: The systematic identification and quantitation of all the metabolic products of a cell, tissue, organ, or organism under varying conditions. The METABOLOME of a cell or organism is a dynamic collection of metabolites which represent its net response to current conditions.Canada: The largest country in North America, comprising 10 provinces and three territories. Its capital is Ottawa.Alberta: A province of western Canada, lying between the provinces of British Columbia and Saskatchewan. Its capital is Edmonton. It was named in honor of Princess Louise Caroline Alberta, the fourth daughter of Queen Victoria. (From Webster's New Geographical Dictionary, 1988, p26 & Room, Brewer's Dictionary of Names, 1992, p12)British Columbia: A province of Canada on the Pacific coast. Its capital is Victoria. The name given in 1858 derives from the Columbia River which was named by the American captain Robert Gray for his ship Columbia which in turn was named for Columbus. (From Webster's New Geographical Dictionary, 1988, p178 & Room, Brewer's Dictionary of Names, 1992, p81-2)Genomics: The systematic study of the complete DNA sequences (GENOME) of organisms.Health Records, Personal: Longitudinal patient-maintained records of individual health history and tools that allow individual control of access.Academies and Institutes: Organizations representing specialized fields which are accepted as authoritative; may be non-governmental, university or an independent research organization, e.g., National Academy of Sciences, Brookings Institution, etc.Work: Productive or purposeful activities.Efficiency: Ratio of output to effort, or the ratio of effort produced to energy expended.Myiasis: The invasion of living tissues of man and other mammals by dipterous larvae.Genetic Code: The meaning ascribed to the BASE SEQUENCE with respect to how it is translated into AMINO ACID SEQUENCE. The start, stop, and order of amino acids of a protein is specified by consecutive triplets of nucleotides called codons (CODON).Drug Users: People who take drugs for a non-therapeutic or non-medical effect. The drugs may be legal or illegal, but their use often results in adverse medical, legal, or social consequences for the users.Work Capacity Evaluation: Assessment of physiological capacities in relation to job requirements. It is usually done by measuring certain physiological (e.g., circulatory and respiratory) variables during a gradually increasing workload until specific limitations occur with respect to those variables.Construction Industry: The aggregate business enterprise of building.Cromakalim: A potassium-channel opening vasodilator that has been investigated in the management of hypertension. It has also been tried in patients with asthma. (Martindale, The Extra Pharmacopoeia, 30th ed, p352)PyransBenzopyrans: Compounds with a core of fused benzo-pyran rings.Potassium Channels: Cell membrane glycoproteins that are selectively permeable to potassium ions. At least eight major groups of K channels exist and they are made up of dozens of different subunits.Calcium Channel Blockers: A class of drugs that act by selective inhibition of calcium influx through cellular membranes.Blood Pressure: PRESSURE of the BLOOD on the ARTERIES and other BLOOD VESSELS.Hypertension, Renal: Persistent high BLOOD PRESSURE due to KIDNEY DISEASES, such as those involving the renal parenchyma, the renal vasculature, or tumors that secrete RENIN.Plethysmography, Whole Body: Measurement of the volume of gas in the lungs, including that which is trapped in poorly communicating air spaces. It is of particular use in chronic obstructive pulmonary disease and emphysema. (Segen, Dictionary of Modern Medicine, 1992)Pulmonary Disease, Chronic Obstructive: A disease of chronic diffuse irreversible airflow obstruction. Subcategories of COPD include CHRONIC BRONCHITIS and PULMONARY EMPHYSEMA.Pulmonary Circulation: The circulation of the BLOOD through the LUNGS.Airway Resistance: Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow.Pulmonary Artery: The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs.

Inhaled NO and almitrine bismesylate in patients with acute respiratory distress syndrome: effect of noradrenalin. (1/32)

The combination of inhaled nitric oxide with almitrine bismesylate has been proposed for the management of acute respiratory distress syndrome in order to divert pulmonary blood flow away from poorly ventilated toward well-ventilated areas. The aims of this prospective and comparative study were to: 1) confirm the beneficial effects on oxygenation of this association; 2) evaluate the haemodynamic effects of this association; and 3) evaluate the influence of noradrenaline (a nonspecific vasoconstrictor) on the modification of gas exchange related to inhaled NO and/or almitrine bismesylate. Forty-one sedated paralysed and ventilated patients were investigated. Haemodynamic and blood gas measurements were performed in a fixed order: baseline; inhalation of NO for 30 min.; intravenous infusion of almitrine bismesylate; and concomitant administration of inhaled NO and almitrine bismesylate. Inhaled NO and almitrine bismesylate increased arterial oxygen tension (Pa,O2)/inspiratory oxygen fraction (FI,O2) (p<0.001). The association of inhaled NO with almitrine bismesylate resulted in a dramatic improvement in Pa,O2/FI,O2 (p<0.0001 versus almitrine bismesylate, p<0.05 versus inhaled NO). In patients receiving noradrenalin (n = 19), almitrine bismesylate had no effect on oxygenation. The present study confirmed that the combination of inhaled NO with almitrine bismesylate improved oxygenation, and demonstrated that almitrine bismesylate has no effect on oxygenation in patients receiving noradrenalin.  (+info)

Effect of inhaled prostacyclin in combination with almitrine on ventilation-perfusion distributions in experimental lung injury. (2/32)

BACKGROUND: Inhaled prostacyclin and intravenous almitrine have both been shown to improve pulmonary gas exchange in acute lung injury (ALI). This study was performed to investigate a possible additive effect of prostacyclin and almitrine on pulmonary ventilation-perfusion (VA/Q) ratio in ALI compared with inhaled prostacyclin or intravenous almitrine alone. METHODS: Experimental ALI was established in 24 pigs by repeated lung lavage. Animals were randomly assigned to receive either 25 inhaled prostacyclin alone, 1 almitrine alone, 25 inhaled prostacyclin in combination with 1 almitrine, or no specific treatment (controls) for 30 min. For each intervention, pulmonary gas exchange and hemodynamics were analyzed and VA/Q distributions were calculated using the multiple inert gas elimination technique. The data was analyzed within and between the groups by analysis of variance for repeated measurements, followed by the Student-Newman-Keuls test for multiple comparison when analysis of variance revealed significant differences. RESULTS: All values are expressed as mean +/- SD. In controls, pulmonary gas exchange, hemodynamics, and VA/Q distribution remained unchanged. With prostacyclin alone and almitrine alone, arterial oxygen partial pressure (PaO2) increased, whereas intrapulmonary shunt (QS/QT) decreased (P < 0.05). Combined prostacyclin and almitrine also increased PaO2 and decreased QS/QT (P < 0.05). When compared with either prostacyclin or almitrine alone, the combined application of both drugs revealed no additional effect in gas exchange or VA/Q distribution. CONCLUSIONS: The authors conclude that, in this experimental model of ALI, the combination of 25 prostacyclin and 1 almitrine does not result in an additive improvement of pulmonary gas exchange or VA/Q distribution when compared with prostacyclin or almitrine alone.  (+info)

Association of oral almitrine and medroxyprogesterone acetate: effect on arterial blood gases in chronic obstructive pulmonary disease. (3/32)

Almitrine (A) and medroxyprogesterone acetate (MA) given separately improve arterial blood gases in some patients with chronic obstructive pulmonary disease (COPD); the aim of this study was to assess the effect of the two drugs given together. Forty-eight patients with irreversible COPD and hypoxaemia were prospectively enrolled into a 14-day run-in period and received single-blind oral treatment with double placebo. Patients whose PaO2 remained stable (less than 10% change; n = 29, 25 males, mean age 65.6 years) were included in a 14-day active treatment period and randomly assigned to three groups. They received double-blind oral treatment with: A (50 mg bid, group A, n = 10); MA (20 mg tid, group MA, n = 9); A (50 mg bid) and MA (20 mg tid, group A+MA, n = 10). Anthropometric and spirometric measurements were similar in the three groups and so were the arterial blood gas values at the beginning and the end of the run-in period. At the end of the active treatment period, blood gas changes (mean+/-SE) were significantly different between groups (P<0.05, Kruskal-Wallis test), with improvement in both hypoxaemia and hypercapnia in group A+MA only: delta PaO2 = 7.4+/-1.9 mmHg, delta PaCO2 = -5.1+/-1.7 m mHg (P<0.05, Wilcoxon test). In short-term treatment, the association of A and MA is more efficient than either drug alone at improving arterial blood gases in COPD patients.  (+info)

Effects of almitrine on diaphragm contractile properties in young and old rats. (4/32)

BACKGROUND: Diaphragm muscle force and fatigue are key factors in the development of respiratory failure. Almitrine is used to improve ventilatory drive and ventilation-perfusion matching in respiratory failure. Recently, it has also been shown to improve diaphragm muscle force and endurance in young rats, but it is not known if this effect persists with ageing. OBJECTIVES: To determine the effects of almitrine on diaphragm contractile properties in young and old rats. METHODS: In young and old rats, isometric contractile properties were measured in strips of isolated diaphragm muscle in physiological saline solution at 30 degrees C with or without almitrine. RESULTS: In young animals, almitrine increased twitch tension, reduced half-relaxation time and increased endurance, but had no effect on tetanic tension, contraction time or tension-frequency relationship. Ageing had no effect on endurance, but did reduce twitch and tetanic tension and contraction and half-relaxation time. Almitrine had no effect on contractile tension and kinetics, tension-frequency relationship or on endurance in the old animals. CONCLUSIONS: Ageing negates the beneficial effects of almitrine on diaphragm muscle force and endurance.  (+info)

An investigation into the mechanism of action of almitrine on isolated rat diaphragm muscle fatigue. (5/32)

BACKGROUND: Previous studies have shown that almitrine bismesylate, a respiratory stimulant which acts on the mitochondrial electron transport chain, enhances recovery of rat diaphragm muscle from fatigue. OBJECTIVES: Our aim is to investigate if the enhanced recovery is due to an anti-oxidant property of almitrine, since the electron transport chain is a major site of intracellular free radical production. METHODS: A low-frequency fatigue protocol was used (30 Hz; 250 ms; delivered once every 2 s for 5 min), and the effects of almitrine before and after fatigue onset were compared to those of the anti-oxidant compound N-acetylcysteine (NAC). RESULTS: Almitrine (6 and 10 microg/ml) given before fatigue gave better recovery rates than postfatigue application. In contrast, NAC (100 microM) application before fatigue onset was not as effective as NAC given immediately after the cessation of the fatigue protocol. However, almitrine (6 microg/ml) completely reversed the reduction in baseline twitch tension brought about by a free-radical-producing mixture of FeCl(3) + ADP (1 mM + 2.5 mM, respectively). CONCLUSION: The results of this study confirm that almitrine enhances recovery from fatigue and, in contrast to NAC prefatigue application, is more effective. Also, almitrine was shown to have an anti-oxidant effect, but it does not act like a typical anti-oxidant.  (+info)

Effect of position, nitric oxide, and almitrine on lung perfusion in a porcine model of acute lung injury. (6/32)

In a porcine model of oleic acid-induced lung injury, the effects of inhaled nitric oxide (iNO) and intravenous almitrine bismesylate (ivALM), which enhances the hypoxic pulmonary vasoconstriction on the distribution of regional pulmonary blood flow (PBF), were assessed. After injection of 0.12 ml/kg oleic acid, 20 anesthetized and mechanically ventilated piglets [weight of 25 +/- 2.6 (SD) kg] were randomly divided into four groups: supine position, prone position, and 10 ppm iNO for 40 min followed by 4 microg x kg(-1) x min(-1) ivALM for 40 min in supine position and in prone position. PBF was measured with positron emission tomography and H(2)15O. The redistribution of PBF was studied on a pixel-by-pixel basis. Positron emission tomography scans were performed before and then 120, 160, and 200 min after injury. With prone position alone, although PBF remained prevalent in the dorsal regions it was significantly redistributed toward the ventral regions (P < 0.001). A ventral redistribution of PBF was also obtained with iNO regardless of the position (P = 0.043). Adjunction of ivALM had no further effect on PBF redistribution. PP and iNO have an additive effect on ventral redistribution of PBF.  (+info)

Effects of almitrine bismesylate on arterial blood gases in patients with chronic obstructive pulmonary disease and moderate hypoxaemia: a multicentre, randomised, double-blind, placebo-controlled study. (7/32)

BACKGROUND: Advanced chronic obstructive pulmonary disease (COPD) generates high costs, especially when patients require domiciliary long-term oxygen therapy (LTOT). Almitrine bismesylate has been shown to improve gas exchange in the lungs. Our hypothesis was that long-term treatment with almitrine might postpone the prescription of LTOT. OBJECTIVE: To evaluate the effects of almitrine sequential treatment on arterial blood gases in COPD patients with moderate hypoxaemia. METHODS: COPD patients with moderate hypoxaemia [partial oxygen tension in arterialised blood (PaO(2)) between 7.33 and 8.66 kPa (56-65 mm Hg)] were investigated. After a 1-month run-in period, patients were given either almitrine 100 mg per day or placebo for sequential treatment for a total of 12 months. RESULTS: 115 patients in a steady state (57 in the almitrine and 58 in the placebo group) were included. Mean age was 60 years, mean forced expiratory volume in 1 s was 34 +/- 13% of predicted and mean PaO(2) was 8.04 +/- 0.5 kPa (60.5 +/- 3.8 mm Hg). 38 patients were lost to follow-up, 23 in the almitrine and 15 in the placebo group. The majority of drop-outs were due to adverse events (AE; 16 in the almitrine and 9 in the placebo group). Almitrine treatment resulted in PaO(2) improvement of 0.43 +/- 0.88 kPa (3.2 +/- 6.6 mm Hg) (p = 0.003). The treatment effect between almitrine and placebo was 0.45 kPa (3.4 mm Hg) (p = 0.003). In the almitrine group, two distinct subgroups were observed: responders (n = 19) and non-responders (n = 38). Almitrine treatment in responders resulted in a clinically significant improvement in PaO(2) of 1.36 +/- 0.7 kPa (10.2 +/- 5.3 mm Hg) (p < 0.0001) and a reduction of partial carbon dioxide tension in arterialised blood. 31 patients experienced serious AE: 17 in the almitrine and 14 in the placebo group. Five patients died during the study (3 in the almitrine and 2 in the placebo group). Most AE occurring during the study were related to underlying disease. Clinical diagnosis of polyneuropathy resulted in the withdrawal of 5 patients in the almitrine group and 3 patients in the placebo group. Four patients in the almitrine group experienced weight loss. CONCLUSIONS: Almitrine treatment of patients with severe COPD and moderate hypoxaemia resulted in a small but significant improvement in PaO(2) over 12 months. A clinically important improvement in gas exchange was observed in 33% of treated patients. These patients may be candidates for long-term treatment.  (+info)

An analysis of the action of an analogue of almitrine bismesylate in the rat model of hypoxic lung disease. (8/32)

Chronically hypoxic (CH) and normoxic control rats were used to assess the action of S9581, a water-soluble analogue of almitrine bismesylate. S9581 increased ventilation (Ve) by 34% in control and 20% in CH rats. During acute hypoxia Ve was raised and S9581 caused a further increase of 20% in both groups. Low doses of S9581 and almitrine enhanced the hypoxic ventilatory response in CH rats while high doses depressed it in both groups. Effects of S9581 on the pulmonary circulation were assessed in the isolated perfused lung of rats. As with almitrine a complex relationship of dose-dependent vasoconstriction and dilatation was revealed. In low doses, S9581 enhanced the hypoxic pulmonary vasoconstrictor response to 2% O2 whilst this was attenuated by high doses in both control and CH rats. S9581 seemed to act like almitrine bismesylate on both the ventilation (peripheral chemoreceptor) and the pulmonary circulation. For studying almitrine-like activity the water solubility of S9581 provides considerable advantages for the researcher.  (+info)

  • 4. Almitrine solvent caused small changes in pulmonary artery pressure and shifted the stimulus-response curve slightly in a parallel fashion. (
  • ORAL almitrine bismesylate has been used for many years to improve gas exchange in patients with chronic obstructive pulmonary disease. (
  • [2,In addition, the association of weight loss and worsening pulmonary hypertension has reduced considerably the use of almitrine for the long-term treatment of patients with chronic obstructive pulmonary disease. (
  • These two side effects were reversed after almitrine was discontinued. (
  • Are peripheral nerve disorders associated with almitrine? (
  • We previously demonstrated that almitrine, a peripheral chemoreceptor stimulant, increased tidal volume (VT), expired minute ventilation (V̇E), and respiratory frequency (f) and decreased inspiratory (TI) and expiratory time (TE) in sleeping adult cats. (
  • Laubie, M., and Schmitt, H., 1980, Long lasting hyperventilation inducedby almitrine: Evidence for a specific effect on carotid and thoracic chemoreceptors Eur. (
  • 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. (
  • Recognizing that apnea is associated with inadequate ventilation and a prolonged TE (failure of the 'inspiratory on-switch'), these results, particularly the increase in f and decrease in TE, suggest that almitrine might be useful in treating apnea in preterm infants. (
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  • We found that a 7.5-mg/kg intraperitoneal dose of almitrine increased f to 135±9% (SE) of base line and decreased TE and TI to 72±8% and 79±8% of base line, respectively. (