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Respiration; International Review of... 2002Diaphragm muscle force and fatigue are key factors in the development of respiratory failure. Almitrine is used to improve ventilatory drive and ventilation-perfusion... (Comparative Study)
Comparative Study
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.
Topics: Aging; Almitrine; Analysis of Variance; Animals; Animals, Newborn; Culture Techniques; Diaphragm; Female; Male; Models, Animal; Muscle Contraction; Muscle Fatigue; Probability; Rats; Rats, Wistar; Reference Values; Sensitivity and Specificity
PubMed: 11844967
DOI: 10.1159/000049374 -
Clinical Science (London, England :... Mar 19921. To test whether almitrine might improve the arterial partial pressure of O2 in patients with chronic obstructive airways disease by improvement of... (Comparative Study)
Comparative Study
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.
Topics: Almitrine; Animals; Blood Pressure; Chlorpheniramine; Cold Temperature; Diethylcarbamazine; Dose-Response Relationship, Drug; Hypoxia; In Vitro Techniques; Male; Oxygen; Propranolol; Pulmonary Artery; Rats; Rats, Inbred Strains; Vasoconstriction
PubMed: 1312410
DOI: 10.1042/cs0820265 -
Annals of Internal Medicine Jan 1987
Clinical Trial Randomized Controlled Trial
Topics: Almitrine; Humans; Oxygen; Oxyhemoglobins; Piperazines
PubMed: 3789561
DOI: 10.7326/0003-4819-106-1-164_1 -
Lancet (London, England) Sep 1988
Clinical Trial
Topics: Aged; Almitrine; Central Nervous System Stimulants; Clinical Trials as Topic; Double-Blind Method; Humans; Male; Peripheral Nervous System Diseases; Piperazines
PubMed: 2900954
DOI: 10.1016/s0140-6736(88)92695-5 -
Lancet (London, England) Nov 1985
Clinical Trial
Topics: Aged; Almitrine; Clinical Trials as Topic; Humans; Middle Aged; Neural Conduction; Peripheral Nervous System Diseases; Piperazines
PubMed: 2866330
DOI: 10.1016/s0140-6736(85)90784-6 -
Lancet (London, England) Nov 1985
Topics: Almitrine; Central Nervous System Stimulants; Humans; Peripheral Nervous System Diseases; Piperazines
PubMed: 2865544
DOI: 10.1016/s0140-6736(85)90936-5 -
Lancet (London, England) Jul 1982
Clinical Trial
Topics: Almitrine; Humans; Piperazines; Sleep Apnea Syndromes
PubMed: 6123901
DOI: 10.1016/s0140-6736(82)91050-9 -
British Journal of Anaesthesia Sep 2005Almitrine combined with inhaled nitric oxide (NO) can prevent hypoxia during one-lung ventilation (OLV). The optimal dose of almitrine that would provide therapeutic... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
BACKGROUND
Almitrine combined with inhaled nitric oxide (NO) can prevent hypoxia during one-lung ventilation (OLV). The optimal dose of almitrine that would provide therapeutic advantage with few side-effects during open-chest OLV has not been established.
METHODS
Forty-two patients undergoing thoracotomy were randomly allocated to three groups: placebo, almitrine 4 microg kg(-1) min(-1) and inhaled NO 10 p.p.m. (ALM4+NO), and almitrine 16 microg kg(-1) min(-1) and inhaled NO 10 p.p.m. (ALM16+NO). Gas exchange, haemodynamic and respiratory variables and plasma concentrations of almitrine and lactate were monitored. Measurements were obtained with the patient awake (baseline), after induction of anaesthesia with two-lung ventilation (control 2LV), 20 min after treatment (2LV+T), and then at 10, 20 and 30 min of OLV (OLV10', OLV20' and OLV30') with FI(O2)1.
RESULTS
In the placebo group, OLV impaired Pa(O2) and increased pulmonary shunt [16 (SD 7) kPa and 42 (10)% respectively]. These improved with ALM4+NO [26 (10) kPa and 31 (7)%; P<0.001]. ALM16+NO further improved PaO2) to 36 (13) kPa (P<0.0001) but gave no improvement in the shunt. Mean pulmonary artery pressure was similar in the placebo and ALM4+NO groups [20 (4) vs 23 (5) mm Hg], whereas it was increased in the ALM16+NO group to 28 (8) mm Hg (P<0.01). Plasma concentrations of almitrine and lactate were unaltered by the treatments.
CONCLUSIONS
Low-dose almitrine (4 microg kg(-1) min(-1)) together with inhaled NO significantly improves oxygenation during open-chest OLV, without modifying pulmonary haemodynamics. An increased dose of almitrine (16 microg kg(-1) min(-1)) with inhaled NO further improves arterial oxygenation, but also increases mean pulmonary artery pressure.
Topics: Adolescent; Adult; Aged; Almitrine; Anthropometry; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Female; Hemodynamics; Humans; Hypoxia; Intraoperative Complications; Male; Middle Aged; Nitric Oxide; Oxygen; Partial Pressure; Prospective Studies; Respiration, Artificial; Thoracotomy
PubMed: 16024585
DOI: 10.1093/bja/aei194 -
Clinical and Experimental Pharmacology... Jun 1986Ventilation to one lobe of lung was reduced in anaesthetized open-chest cats and dogs to simulate the ventilation/perfusion (V/Q) mismatching of chronic lung disease....
Ventilation to one lobe of lung was reduced in anaesthetized open-chest cats and dogs to simulate the ventilation/perfusion (V/Q) mismatching of chronic lung disease. Blood flow to this lobe fell less than ventilation; thus lobar V/Q diminished. In seven cats almitrine (0.5 mg/kg + 10 micrograms/kg per min, i.v.) caused a rise in pulmonary artery pressure (PPA), increased flow through the hypoventilated lobe in six out of seven cats and both increased or decreased lobar vascular resistance (PVR); the lobar V/Q ratio therefore fell. Arterial and lobar venous oxygen tension (PO2) fell. In five dogs almitrine caused a rise in PPA and PVR but lobar flow changes were variable. Arterial and lobar venous PO2 fell. With fixed ventilation, almitrine failed to improve V/Q matching; there was no improvement in gas exchange in the hypoventilated lobe. In eight dogs the hypoventilated lobe was perfused at constant flow with right atrial blood (i.e. while V/Q was held constant). Almitrine caused a rise in perfusion pressure, vasoconstriction, followed, in five out of eight dogs, by vasodilatation. In six similar cat preparations, vasoconstriction but not vasodilatation was clearly shown. In two cats dilatation after almitrine was demonstrated during ventilation with Nitrogen. In all experiments there was no significant effect of the solvent. Thus the dual action of almitrine seen in other species was seen in a proportion of cats and dogs. Results do not support the view that improved arterial gas tensions in patients after almitrine are attributable to diversion of blood flow away from hypoxic lung. Alternative mechanisms are discussed.
Topics: Almitrine; Animals; Cats; Dogs; Lung Diseases, Obstructive; Oxygen; Piperazines; Pulmonary Circulation; Species Specificity; Vascular Resistance; Ventilation-Perfusion Ratio
PubMed: 3757310
DOI: 10.1111/j.1440-1681.1986.tb00926.x -
Thorax Jul 1991The effects of oral almitrine bismesylate, a respiratory stimulant that acts on peripheral arterial chemoreceptors, was studied in patients with chronic obstructive... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
The effects of oral almitrine bismesylate, a respiratory stimulant that acts on peripheral arterial chemoreceptors, was studied in patients with chronic obstructive airways disease and hypoxaemic cor pulmonale. Twenty three patients admitted to hospital with an acute exacerbation of ventilatory failure were randomised to receive either almitrine 100 mg twice a day reducing to 50 mg twice a day over 48 hours or placebo in addition to conventional treatment. On admission the mean (SE) values for blood gas tensions were PaO2 4.8 (0.3) and PaCO2 7.7 (0.3) kPa in the 12 patients who received almitrine and PaO2 4.9 (0.1) and PaCO2 7.6 (0.3) kPa in the 11 who received placebo. After three hours of oxygen therapy at 1 1/min there was a similar rise in PaO2 in both groups, 6.4 (0.2) kPa in those receiving almitrine and 6.6 (0.4) kPa in those receiving placebo. After 24 hours of oxygen therapy values of PaO2 were again similar at 6.3 (0.8) kPa and 6.7 (2.2) kPa respectively. Arterial blood gas tensions improved during the study in those who survived but no significant differences were apparent between the two groups. There were six deaths, five in the almitrine group and one in the placebo group. There were no differences between the groups in respiratory rate, results of spirometry, oxygen requirement, or degree of dyspnoea (on visual analogue scale). The results did not show any benefit from oral almitrine in patients with acute respiratory failure secondary to chronic obstructive airways disease. Plasma almitrine concentrations, however, were often below the optimum therapeutic range, suggesting impaired drug absorption.
Topics: Administration, Oral; Aged; Aged, 80 and over; Almitrine; Carbon Dioxide; Double-Blind Method; Female; Forced Expiratory Volume; Humans; Lung Diseases, Obstructive; Male; Middle Aged; Oxygen; Pulmonary Heart Disease; Respiratory Insufficiency; Vital Capacity
PubMed: 1908604
DOI: 10.1136/thx.46.7.493