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Journal of Applied Physiology... Jul 1997The effects of almitrine bimesylate and doxapram HCl on isometric force produced by in vitro rat diaphragm were studied during direct muscle activation at 37 degrees C....
The effects of almitrine bimesylate and doxapram HCl on isometric force produced by in vitro rat diaphragm were studied during direct muscle activation at 37 degrees C. Doxapram and almitrine ameliorate respiratory failure clinically by indirectly increasing phrenic nerve activity. This study was carried out to investigate possible direct actions of these agents on the diaphragm before and after fatigue of the fibers. Two age groups of animals were chosen [6-14 wk (group 1) and 50-55 wk (group 2)] because it is known that increasing age decreases a muscle fiber's resistance to fatigue. Muscle strips were isolated from both group 1 and group 2 and directly stimulated (2-ms pulse duration, 5-15 V) to produce twitch tensions of 1.3 and 2.1 N/cm2, respectively. At low concentrations, doxapram (=20 microg/ml) and almitrine (=12 microg/ml) had no effect on twitch contraction or 100-Hz tetanic tension. However, 40 microg/ml doxapram and 30 microg/ml almitrine increased twitch tension by 9.0 +/- 1.4 and 11.6 +/- 1.9%, respectively, in animals of group 2 (n = 5). A fatigue protocol consisting of low-frequency stimulation (30-Hz trains, 250-ms duration every 2 s for 5 min) caused a reduction of twitch tension in animals of group 1 (48 +/- 4% of control) and group 2 (28 +/- 4% of control). At 90 min postfatigue, the twitch tension recovered to 72 +/- 3 and 42 +/- 2% of control values in group 1 and group 2, respectively. In the presence of doxapram (20 microg/ml), there was a significant increase in the recovery of twitch tension at 90 min in group 1 and group 2 (84.5 +/- 3.2 and 80.1 +/- 2.8%, respectively) compared with controls at 90 min postfatigue. In the presence of almitrine (12 microg/ml), there was a full recovery from fatigue in group 1 animals (100% of control) and a recovery to 95.6 +/- 2.1% of control in group 2 animals at 90 min. These results demonstrate a significant improvement in the rapidity and magnitude of recovery from fatigue in the rat diaphragm muscle in the presence of both doxapram and, especially, almitrine. These effects may be due to changes in intracellular calcium, ADP/ATP ratios, or oxygen free radical scavenging.
Topics: Almitrine; Animals; Diaphragm; Doxapram; Electric Stimulation; In Vitro Techniques; Isometric Contraction; Male; Muscle Contraction; Muscle Relaxation; Rats; Rats, Wistar; Respiratory System Agents
PubMed: 9216944
DOI: 10.1152/jappl.1997.83.1.52 -
Anesthesia and Analgesia Aug 2019This single-center case series investigated the effect of almitrine infusion on PaO2/fraction of inspired oxygen (FIO2) in 25 patients on veno-venous extracorporeal... (Observational Study)
Observational Study
This single-center case series investigated the effect of almitrine infusion on PaO2/fraction of inspired oxygen (FIO2) in 25 patients on veno-venous extracorporeal membrane oxygenation for severe acute respiratory distress syndrome. A positive trial was defined as an increase of PaO2/FIO2 ratio ≥20%. Thirty-two trials were performed. Twenty (62.5%, 95% confidence interval, 37.5%-75%) trials in 18 patients were positive, with a median PaO2/FIO2 ratio increase of 35% (25%-43%). A focal acute respiratory distress syndrome and inhaled nitric oxide therapy were more frequent in patients with a positive response to almitrine. We observed no complications of almitrine use.
Topics: Adult; Almitrine; Extracorporeal Membrane Oxygenation; Female; Humans; Infusions, Intravenous; Male; Middle Aged; Recovery of Function; Respiration; Respiratory Distress Syndrome; Respiratory System Agents; Retrospective Studies; Time Factors; Treatment Outcome
PubMed: 29337729
DOI: 10.1213/ANE.0000000000002786 -
Biochimica Et Biophysica Acta Aug 1989At low concentrations, almitrine inhibits yeast cell multiplication by acting on oxidative metabolism. Studies on isolated mitochondria display the following features:...
At low concentrations, almitrine inhibits yeast cell multiplication by acting on oxidative metabolism. Studies on isolated mitochondria display the following features: (i) almitrine inhibits ATPase activity and decreases ATP/O ratio during oxidative phosphorylation; (ii) no direct effect on respiration can be evidenced; (iii) ATP/O value decreases without any change in the magnitude of delta p; (iv) the higher the ATP synthesis and respiratory fluxes, the larger is the decrease in ATP/O ratio induced by almitrine. These results indicate that almitrine does not act as a classical protonophoric uncoupler nor as previously studied non protonophoric uncouplers (e.g., general anesthetics). Our data show a direct inhibitory effect of almitrine on ATPase-ATP synthase complex. But, in contrast to the classical inhibitors of this complex, almitrine decreases the ATP/O ratio in a flux-dependent manner. Thus, almitrine could induce either an intrinsic uncoupling of H+/-ATPase (i.e., slip in this proton pump) or a change in the mechanistic H+/ATP stoichiometry at the ATPase level.
Topics: Adenosine Triphosphate; Almitrine; Cell Division; Energy Metabolism; Growth Inhibitors; Kinetics; Mitochondria; Oxidative Phosphorylation; Piperazines; Proton-Translocating ATPases; Saccharomyces cerevisiae; Uncoupling Agents
PubMed: 2527061
DOI: 10.1016/s0005-2728(89)80339-1 -
European Neurology 1995
Review
Topics: Aging; Almitrine; Animals; Brain; Cerebrovascular Disorders; Drug Combinations; Electroencephalography; Humans; Neuroprotective Agents; Rats; Secologanin Tryptamine Alkaloids; Yohimbine
PubMed: 8529728
DOI: 10.1159/000119497 -
Revue Des Maladies Respiratoires 1985
Topics: Almitrine; Bronchitis; Central Nervous System Stimulants; Humans; Kinetics; Paresthesia; Piperazines
PubMed: 2870541
DOI: No ID Found -
Revista Clinica Espanola Feb 1990Almitrine dimesylate is a peripheral respiratory stimulant which is effective both on long and short term treatment of chronic obstructive lung disease. The individual... (Review)
Review
Almitrine dimesylate is a peripheral respiratory stimulant which is effective both on long and short term treatment of chronic obstructive lung disease. The individual therapeutic response, however, is very variable and approximately 25% of patients might not respond to treatment. The recommended doses are 50-100 mg per day during two months, followed by a resting month. Higher doses or longer treatments could provoke high serum levels which in turn would increase the risk of pulmonary hypertension and peripheral neuropathies. Almitrine is not commercialized in Spain as a single drug or for the cited indications.
Topics: Almitrine; Humans; Lung Diseases, Obstructive; Peripheral Nervous System Diseases
PubMed: 2158666
DOI: No ID Found -
Journal of Applied Physiology... Oct 1990Almitrine bimesylate is a potent and long-lasting respiratory stimulant in adult species. It acts by stimulating the peripheral chemoreceptors, where it has been shown...
Almitrine bimesylate is a potent and long-lasting respiratory stimulant in adult species. It acts by stimulating the peripheral chemoreceptors, where it has been shown to accumulate specifically, although its exact mechanism of action is uncertain. In the fetal lamb, however, it produces a profound inhibition of breathing even after denervation of the peripheral chemoreceptors. In this respect its action is similar to hypoxia. To investigate whether almitrine is hypoxia mimetic, we examined the effect of almitrine in nine fetal lambs of 120-130 days gestation. Five had lesions in the lateral pons that changed the fetal depressive response to hypoxia to one of stimulation. In the remaining four fetuses, the lesions did not bilaterally encompass the appropriate area of the pons; thus they still showed the normal fetal depressive response to hypoxia and so acted as controls. Almitrine (10 mg iv) caused a pronounced stimulation of breathing that lasted 406 +/- 26 min in all five fetuses with lesions that caused a stimulatory response to hypoxia. However, in the remaining four fetuses, in which the response to hypoxia was inhibitory, almitrine caused an inhibition of breathing that lasted 184 +/- 28 min. We conclude that the action of almitrine is like that of hypoxia and that, because it acts specifically on the chemoreceptors, it may prove to be a useful tool in the study of possible central chemoreceptor mechanisms.
Topics: Almitrine; Animals; Chemoreceptor Cells; Denervation; Electrooculography; Female; Fetal Hypoxia; Pons; Pregnancy; Respiration; Sheep; Stimulation, Chemical
PubMed: 2262450
DOI: 10.1152/jappl.1990.69.4.1330 -
Revista de Igiena, Bacteriologie,... 1987
Review
Topics: Almitrine; Animals; Bronchitis; Central Nervous System Stimulants; Chronic Disease; Humans; Lung Diseases; Piperazines
PubMed: 2894713
DOI: No ID Found -
Revue Des Maladies Respiratoires 1985Almitrine bismesilate (Vectarion) is characterised by its specific activity on carotid and aortic chemoreceptors. A simultaneous study of the ventilatory and blood gas...
Almitrine bismesilate (Vectarion) is characterised by its specific activity on carotid and aortic chemoreceptors. A simultaneous study of the ventilatory and blood gas changes in the anaesthetised dog has shown a dissociation between these two effects. At a dose of 10 to 30 micrograms/kg IV Almitrine bismesilate induces a significant rise in the PaO2 whereas no change in the ventilatory output is observed. A significant transitory rise in the pulmonary arterial pressure also appears at these doses. The juxta position of these results suggests that a feeble doses Almitrine bismesilate improves the blood gases of the arterial blood by a re-distribution of the pulmonary blood flow. Clinical pharmacological studies carried out in bronchitic patients have shown an improvement in the distribution of ventilation perfusion ratios VA/Q by Almitrine bismesilate. These experiments were carried out in animals in order to determine whether the drug had a preferential action on one or other side of the VA/Q ratio. Whereas in an animal with intact lungs, Almitrine bismesilate potentiates hypoxia induced vaso-constriction, in animals whose lungs are ventilated in a heterozygous fashion in such a way as to reproduce zones with a shunt effect, the potentiation of hypoxic vasoconstriction was not again found. At low doses in the hypoxic rat Almitrine bismesilate increases alveolar ventilation (VH) by a significant rise in tidal volume and inspiratory output (VT/TI) without increasing external ventilation. Overall the rise of PaO2 induced by Almitrine bismesilate at low doses may be accompanied by a similar effect on the pulmonary circulation noted in the anaesthetised dog. In the hypoxic rat, it is changes in the alveolar ventilation that are observed.(ABSTRACT TRUNCATED AT 250 WORDS)
Topics: Almitrine; Animals; Bronchitis; Cats; Central Nervous System Stimulants; Chemoreceptor Cells; Dogs; Piperazines; Pulmonary Circulation; Pulmonary Gas Exchange; Rabbits; Rats; Ventilation-Perfusion Ratio
PubMed: 2870542
DOI: No ID Found -
The American Review of Respiratory... May 1988Almitrine improves ventilation/perfusion relationships (VA/Q) in COPD, but its effects in ARDS, in which VA/Q mismatching is the cause of severe hypoxemia, are not...
Almitrine improves ventilation/perfusion relationships (VA/Q) in COPD, but its effects in ARDS, in which VA/Q mismatching is the cause of severe hypoxemia, are not known. The effects of almitrine on pulmonary gas exchange and circulation were assessed in 9 patients with ARDS who were sedated, paralyzed, and mechanically ventilated at constant FlO2 (range, 0.48 to 0.74). Systemic and pulmonary hemodynamics, conventional gas exchange, and the VA/Q distribution by the multiple inert gas elimination technique (MIGT) were measured before (baseline), during (ALM 15), at the end of (ALM 30), and at 30-min intervals after (POSTALM 30, 60, and 90) the intravenous infusion of 0.5 mg/kg body weight of almitrine over 30 min. Almitrine significantly increased PaO2 from 78 +/- 15 mm Hg to 140 +/- 49 at ALM 15 and 138 +/- 52 at ALM 30. AaPO2 and QS/QT decreased during the administration of the drug. The MIGT showed that almitrine redistributed pulmonary blood flow from shunt areas (reduction from 29 +/- 11 to 17 +/- 11% of QT) to lung units with normal VA/Q ratios (increase from 63 +/- 9 to 73 +/- 6% of QT). The Ppa increased from 26 +/- 5 to 30 +/- 5 mm Hg without changes in QT. Changes were transient, returning toward baseline 30 min after stopping the infusion of the drug. Almitrine significantly reduced the VA/Q inequalities present in ARDS and may be useful in the management of those patients.
Topics: Adult; Aged; Almitrine; Cardiac Output; Female; Humans; Male; Middle Aged; Oxygen; Piperazines; Pulmonary Circulation; Pulmonary Gas Exchange; Respiratory Distress Syndrome; Vascular Resistance; Ventilation-Perfusion Ratio
PubMed: 3195804
DOI: 10.1164/ajrccm/137.5.1062