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Minerva Anestesiologica May 2014Lung ultrasound can be used at bedside to assess initial lung morphology in hypoxemic patients. We hypothesized that blood flow in consolidated lung and therefore...
BACKGROUND
Lung ultrasound can be used at bedside to assess initial lung morphology in hypoxemic patients. We hypothesized that blood flow in consolidated lung and therefore effects of inhaled nitric oxide (iNO) and intravenous almitrine could be directly assessed using Doppler transesophageal echocardiography (TEE).
METHODS
We conducted a prospective study including 13 ALI patients with consolidated left lower lobe (LLL). Regional arterial and venous flow signals within the consolidation were recorded with TEE using Doppler at baseline, after iNO (5 ppm), almitrine (4 μg/kg/min) and their combination. Pulmonary shunt (Qs/Qt) was measured using a Swan-Ganz catheter. Arterial and venous velocity time integral (VTI), peak velocity (Vmax) and mean velocity (Vmean) were measured. Patients were responders if PaO2 basal value increased by 20% after iNO or almitrine.
RESULTS
In 7 NO responders, iNO decreased regional arterial VTI (8.1±1.9 vs. 6.7±1.6, P<0.05). In 8 almitrine responders, almitrine decreased regional arterial and venous VTI (from 6.7±2.0 to 4.5±2.3 cm and from 12.3±5.4 to 7.5±3.8 cm, respectively, P<0.05). For all patients, combination of iNO and almitrine decreased regional arterial and venous VTI (from 7.3±0.3 to 4.1±0.3 cm and from 12.6±0.7 to 6.7±0.8 cm, respectively, P<0.05). Arterial and venous Vmean and Vmax significantly decreased. Variations of arterial VTI and venous Vmean were correlated to variations of Qs/Qt (r=.71, P<.001 and r=.62, P<.01, respectively).
CONCLUSION
Doppler of consolidated LLL allows assessment of regional pulmonary circulation in ICU settings. It detects changes in flow profiles resulting from the administration of NO and/or almitrine. Further applicability remains to be determined.
Topics: Acute Lung Injury; Administration, Inhalation; Aged; Almitrine; Bronchodilator Agents; Echocardiography, Transesophageal; Female; Humans; Injections, Intravenous; Male; Middle Aged; Nitric Oxide; Pulmonary Circulation; Respiratory Distress Syndrome; Respiratory System Agents
PubMed: 24299918
DOI: No ID Found -
British Journal of Anaesthesia Jan 2023Intrapulmonary shunt is a major determinant of oxygenation in thoracic surgery under one-lung ventilation. We reviewed the effects of available treatments on shunt,... (Meta-Analysis)
Meta-Analysis
Impact of pharmacological interventions on intrapulmonary shunt during one-lung ventilation in adult thoracic surgery: a systematic review and component network meta-analysis.
BACKGROUND
Intrapulmonary shunt is a major determinant of oxygenation in thoracic surgery under one-lung ventilation. We reviewed the effects of available treatments on shunt, Pao/FiO and haemodynamics through systematic review and network meta-analysis.
METHODS
Online databases were searched for RCTs comparing pharmacological interventions and intrapulmonary shunt in thoracic surgery under one-lung ventilation up to March 30, 2022. Random-effects (component) network meta-analysis compared 24 treatments and 19 treatment components. The Confidence in Network Meta-Analysis (CINeMA) framework assessed evidence certainty. The primary outcome was intrapulmonary shunt fraction during one-lung ventilation.
RESULTS
A total of 55 RCTs were eligible for systematic review (2788 participants). The addition of NO (mean difference [MD]=-15%; 95% confidence interval [CI], -25 to -5; P=0.003) or almitrine (MD=-13%; 95% CI, -20 to -6; P<0.001) to propofol anaesthesia were efficient at decreasing shunt. Combined epidural anaesthesia (MD=3%; 95% CI, 1-5; P=0.005), sevoflurane (MD=5%; 95% CI, 2-8; P<0.001), isoflurane (MD=6%; 95% CI, 4-9; P<0.001), and desflurane (MD=9%; 95% CI, 4-14; P=0.001) increased shunt vs propofol. Almitrine (MD=147 mm Hg; 95% CI, 58-236; P=0.001), dopexamine (MD=88 mm Hg; 95% CI, 4-171; P=0.039), and iloprost (MD=81 mm Hg; 95% CI, 4-158; P=0.038) improved Pao/FiO. Certainty of evidence ranged from very low to moderate.
CONCLUSIONS
Adding NO or almitrine to propofol anaesthesia reduced intrapulmonary shunt during one-lung ventilation. Halogenated anaesthetics increased shunt in comparison with propofol. The effects of NO, iloprost, and dexmedetomidine should be investigated in future research. NO results constitute a research hypothesis currently not backed by any direct evidence. The clinical availability of almitrine is limited.
SYSTEMATIC REVIEW PROTOCOL
PROSPERO CRD42022310313.
Topics: Adult; Humans; Almitrine; Iloprost; Network Meta-Analysis; One-Lung Ventilation; Propofol; Thoracic Surgery
PubMed: 36939497
DOI: 10.1016/j.bja.2022.08.039 -
Pharmaceutics Aug 2022is a protozoan that infects up to a third of the world's population. This parasite can cause serious problems, especially if a woman is infected during pregnancy, when...
is a protozoan that infects up to a third of the world's population. This parasite can cause serious problems, especially if a woman is infected during pregnancy, when toxoplasmosis can cause miscarriage, or serious complications to the baby, or in an immunocompromised person, when the infection can possibly affect the patient's eyes or brain. To identify potential drug candidates that could counter toxoplasmosis, we selected 13 compounds which were pre-screened in silico based on the proteome of to be evaluated in vitro against the parasite in a cell-based assay. Among the selected compounds, three demonstrated in vitro anti- activity in the nanomolar range (almitrine, bortezomib, and fludarabine), and ten compounds demonstrated anti- activity in the micromolar range (digitoxin, digoxin, doxorubicin, fusidic acid, levofloxacin, lomefloxacin, mycophenolic acid, ribavirin, trimethoprim, and valproic acid). Almitrine demonstrated a Selectivity Index (provided by the ratio between the Half Cytotoxic Concentration against human foreskin fibroblasts and the Half Effective Concentration against tachyzoites) that was higher than 47, whilst being considered a lead compound against . Almitrine showed interactions with the Na/K ATPase transporter for and , indicating a possible mechanism of action of this compound.
PubMed: 36015260
DOI: 10.3390/pharmaceutics14081634 -
Anesthesiology Oct 1998Intravenous almitrine, which augments hypoxic pulmonary vasoconstriction, is used for short-term improvement of arterial oxygenation. However, recent research has... (Clinical Trial)
Clinical Trial
BACKGROUND
Intravenous almitrine, which augments hypoxic pulmonary vasoconstriction, is used for short-term improvement of arterial oxygenation. However, recent research has suggested a potentially harmful effect on lactate metabolism and hepatic function.
METHODS
Arterial oxygenation, hemodynamic parameters, plasma lactate, and hepatic function were monitored prospectively in 25 patients with acute lung injury (defined as a ratio of arterial oxygen pressure to inspiratory oxygen fraction < or = 150 mmHg) who where treated with intravenous almitrine. In 21 of 25 patients, acute lung injury was related to primary lung lesions, including pneumonia, postcardiosurgical atelectasis, and lung contusions.
RESULTS
Intravenous almitrine increased the ratio of arterial oxygen pressure to inspiratory oxygen fraction from 93 +/- 33 mmHg to 207 +/- 107 mmHg (mean +/- SD). In eight patients (three men), the plasma lactate concentration increased by an average of +3.5 +/- 1.8 mM, and the pH and bicarbonate concentration both decreased during the first 24 h of treatment. In this group of patients, the total bilirubin concentration was elevated before almitrine administration, and the results of other hepatic function tests, such as aspartate aminotransferase, alanine aminotransferase, and prothrombin time, were altered by almitrine administration. Therefore, intravenous almitrine was discontinued. Lactic acidosis and hepatic dysfunction improved. In the other 17 patients (14 men), the plasma lactate concentration and the hepatic function tests remained unaltered during intravenous almitrine therapy for > 60 h. Univariate and multivariate analyses revealed that an abnormal plasma concentration of total bilirubin before almitrine administration and female gender were the two factors significantly linked with lactic acidosis during almitrine infusion.
CONCLUSIONS
This study confirms that intravenous almitrine greatly improves arterial oxygenation in patients with acute lung injury but may also induce lactic acidosis and hepatic dysfunction. The coexistence of lactic acidosis and hepatic dysfunction in the same patients strongly suggests that the liver is the primary source of intravenous almitrine-induced lactic acidosis.
Topics: Acidosis, Lactic; Acute Disease; Adolescent; Adult; Aged; Almitrine; Analysis of Variance; Bilirubin; Chemical and Drug Induced Liver Injury; Female; Humans; Injections, Intravenous; Lactic Acid; Lung Diseases; Male; Middle Aged; Oxygen; Partial Pressure; Respiratory System Agents
PubMed: 9777998
DOI: 10.1097/00000542-199810000-00005 -
Journal of the Royal Society of Medicine Jan 1985
Review
Topics: Albuterol; Almitrine; Ampicillin; Bronchitis; Carbon Dioxide; Humans; Hypoxia; Oxygen Inhalation Therapy; Partial Pressure; Piperazines; Pulmonary Emphysema; Pulmonary Gas Exchange; Respiration, Artificial; Respiratory Insufficiency; Terbutaline
PubMed: 3918168
DOI: 10.1177/014107688507800112 -
Anesthesiology Nov 1998The partition of pulmonary blood flow between normal and shunting zones is an important determinant of oxygen tension in arterial blood (PaO2). The authors hypothesized... (Clinical Trial)
Clinical Trial
BACKGROUND
The partition of pulmonary blood flow between normal and shunting zones is an important determinant of oxygen tension in arterial blood (PaO2). The authors hypothesized that the combination of inhaled nitric oxide (iNO) and almitrine infusion might have additional effects related to their pharmacologic properties to improve PaO2. Such a combination was tested in patients with hypoxia caused by focal lung lesions, distinct from the acute respiratory distress syndrome.
METHODS
Fifteen patients with hypoxic focal lung lesions despite optimal therapy were included and successively treated with (1) 5 ppm iNO, (2) low-dose almitrine infusion (5.5 +/- 1.7 microg x kg(-1) min(-1)) during iNO, and (3) almitrine infusion alone (with NO turned off). Then iNO was reintroduced and we studied the effect of the coadministration in reducing the fractional concentration of oxygen in inspired gas (FI(O2)) and positive end-expiratory pressure (PEEP) levels. Changes in blood gases and pulmonary and systemic hemodynamics were measured.
RESULTS
Systemic hemodynamic variables remained stable in all protocol conditions. Use of iNO improved arterial oxygenation and decreased intrapulmonary shunt. Almitrine similarly improved PaO2 but increased pulmonary artery pressure and right atrial pressure. Coadministration of iNO and almitrine improved PaO2 compared with each drug alone and with control. All patients responded (that is, they had at least a +30% increase in PaO2) to this coadministration. When the drug combination was continued, FI(O2) and PEEP could be reduced over 8 h. The hospital mortality rate was 33% and unrelated to hypoxia.
CONCLUSIONS
In hypoxemic focal lung lesions, iNO or low-dose almitrine markedly improved PaO2 to a similar extent. Furthermore, the coadministration amplified the PaO2 increase at a level that allowed reductions in FI(O2) and PEEP levels.
Topics: Administration, Inhalation; Adult; Aged; Almitrine; Blood Pressure; Cardiac Catheterization; Female; Humans; Hypoxia; Infusions, Intravenous; Lung Diseases; Male; Middle Aged; Nitric Oxide; Pulmonary Gas Exchange; Respiratory Function Tests; Respiratory System Agents
PubMed: 9822004
DOI: 10.1097/00000542-199811000-00016 -
Pharmaceuticals (Basel, Switzerland) Feb 2024Leishmaniasis, a neglected tropical disease, poses a significant global health challenge, necessitating the urgent development of innovative therapies. In this study, we...
Leishmaniasis, a neglected tropical disease, poses a significant global health challenge, necessitating the urgent development of innovative therapies. In this study, we aimed to identify compounds from the COVID Box with potential efficacy against two species, laying the foundation for future chemical development. Four promising molecules were discovered, demonstrating notable inhibitory effects against and . Our study revealed that bortezomib, almitrine, and terconazole induced a significant decrease in mitochondrial membrane potential, while the above compounds and ABT239 induced plasma permeability alterations, chromatin condensation, and reactive oxygen species accumulation, indicating early apoptosis in promastigotes, preventing inflammatory responses and tissue damage, thereby improving patient outcomes. Furthermore, ADME predictions revealed favorable pharmacokinetic profiles for all compounds, with bortezomib and ABT239 standing out as potential candidates. These compounds exhibited intestinal absorption, blood-brain barrier penetration (excluding bortezomib), and good drug-likeness for bortezomib and ABT239. Toxicity predictions for CYP-inhibition enzymes favored bortezomib as the safest candidate. In conclusion, our study identifies bortezomib as a promising aspirant for leishmaniasis treatment, demonstrating potent antiparasitic activity, favorable pharmacokinetics, and low toxicity. These findings emphasize the potential repurposing of existing drugs for neglected diseases and highlight the importance of the COVID Box in drug discovery against tropical diseases.
PubMed: 38543052
DOI: 10.3390/ph17030266 -
British Medical Journal (Clinical... Nov 1984
Topics: Adrenergic beta-Agonists; Almitrine; Bronchitis; Humans; Hypertension, Pulmonary; Nifedipine; Piperazines; Pulmonary Emphysema; Pulmonary Heart Disease; Smoking; Vasodilator Agents
PubMed: 6149785
DOI: 10.1136/bmj.289.6456.1398 -
The Journal of Physiology Mar 19921. In four awake dogs we measured EMG activity of three inspiratory and four expiratory muscles during sustained central chemoreceptor stimulation (CO2 inhalation), and... (Comparative Study)
Comparative Study
1. In four awake dogs we measured EMG activity of three inspiratory and four expiratory muscles during sustained central chemoreceptor stimulation (CO2 inhalation), and peripheral chemoreceptor stimulation (intravenous infusion of almitrine bismesylate (almitrine)). By using this selective pharmacological stimulation of the peripheral chemoreceptors and reversibly cold-blocking pulmonary stretch receptors, we were able to determine the effects of each type of stimulation on respiratory muscle recruitment in the absence of such complicating influences as pulmonary stretch receptor feedback, cerebral hypoxia or hypocapnia, and differences in breathing pattern. 2. During 10 min of steady-state hyperpnoea (minute ventilation VI, approximately twice eupnoea) caused by either hypercapnia or isocapnic stimulation of the carotid bodies with almitrine, all three inspiratory and all four expiratory muscles demonstrated significant and sustained elevations in EMG activity. 3. With both types of chemoreceptor stimulation, as tidal volume, VT, increased, so did the mean electrical activities of the crural diaphragm (r = 0.88), costal diaphragm (r = 0.93), parasternals (r = 0.82), triangularis sterni (r = 0.74), transversus abdominis (r = 0.77), external obliques (r = 0.68) and internal intercostals (r = 0.75). 4. In each dog, the response of ventilation and of the diaphragmatic EMG to a given level of central or peripheral chemoreceptor stimulation is highly reproducible from one test day to the next. On the other hand, accessory inspiratory and expiratory abdominal and rib cage muscles in two of the four dogs showed highly significant changes from day to day in the amount of their EMG activity at any given VT. 5. During steady-state ventilatory stimulation, 2 min intervals were chosen during which the two types of chemoreceptor stimulation had caused hyperpnoeas with similar values for VT, total time per breath (TTOT) and inspiratory time divided by the total time (TI/TTOT). Comparison of EMG activities during these matched hyperpnoeas revealed that there were no differences in the activities of any of the muscles between the two forms of stimulation. We conclude that peripheral chemoreceptor stimulation causes significant and sustained recruitment of expiratory muscles even in the absence of pulmonary feedback and that both expiratory and inspiratory muscles are recruited to the same extent during peripheral chemoreceptor stimulation as they are during an identical hyperpnoea caused by central chemoreceptor stimulation.
Topics: Almitrine; Animals; Carbon Dioxide; Chemoreceptor Cells; Dogs; Electromyography; Female; Respiratory Muscles; Tidal Volume; Time Factors
PubMed: 1593481
DOI: 10.1113/jphysiol.1992.sp019061 -
Anesthesiology Nov 1995Inhaled nitric oxide, a selective pulmonary vasodilator, in combination with intravenous almitrine, a selective pulmonary vasoconstrictor, markedly improves arterial... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
BACKGROUND
Inhaled nitric oxide, a selective pulmonary vasodilator, in combination with intravenous almitrine, a selective pulmonary vasoconstrictor, markedly improves arterial oxygenation in 50-60% of patients with acute lung injury. The goal of this study was to assess dose response of inhaled nitric oxide with and without almitrine in patients with acute respiratory distress syndrome responding to nitric oxide.
METHODS
Six critically ill patients (aged 44 +/- 7 yr) were studied during early stage of their acute respiratory failure (Murray score: 2.6 +/- 0.1). All responded to 15 parts per million (ppm) of inhaled nitric oxide by an increase in Pao2 of at least 40 mmHg at FIo2 1. Hemodynamic and respiratory parameters were recorded continuously from pulmonary artery and systemic catheters. Inspiratory, expiratory, and mean intratracheal nitric oxide concentrations were monitored continuously using a fast response time chemiluminescence apparatus (NOX 4000, Sérès, Aix-en-provence, France). On day 1, 6 inspiratory concentrations of nitric oxide were randomly administered: 0.15, 0.45, 1.5, 4.5, 15, and 45 ppm to determine the dose response of inhaled nitric oxide on Pao2, pulmonary shunt, mean pulmonary artery pressure, and pulmonary vascular resistance index. On day 2, a continuous intravenous infusion of almitrine at a dose of 16 micrograms.kg-1.min-1 was administered and dose response to inhaled nitrix oxide was repeated according to the same protocol as during day 1. A constant FIo2 of 0.85 was used throughout the study.
RESULTS
Nitric oxide induced a dose-dependent increase in Pao2 for inspiratory nitric oxide concentrations ranging between 0.15 and 1.5 ppm. Almitrine increased Pao2/FIo2 from 161 +/- 30 to 251 +/- 45 mmHg (P < 0.001) and pulmonary vascular resistance index from 455 +/- 185 to 527 +/- 176 dyn.s.cm-5.m2 (P < 0.05), and decreased pulmonary shunt (Qs/QT) from 35 +/- 2 to 33 +/- 3% (P < 0.001). During almitrine combined with nitric oxide, a dose-dependent increase in Pao2 was observed for inspiratory nitric oxide concentrations ranging between 0.15 and 1.5 ppm. Almitrine plus nitric oxide 1.5 ppm increased Pao2/FIo2 from 161 +/- 30 to 355 +/- 36 mmHg (P < 0.001), decreased Qs/QT from 35 +/- 2 to 24 +/- 2% (P < 0.001), pulmonary vascular resistance index from 455 +/- 185 to 385 +/- 138 dyn.s.cm-5.m2 (P < 0.05), and mean pulmonary artery pressure from 31 +/- 4 to 28 +/- 4 mmHg (P < 0.001).
CONCLUSIONS
In 6 patients with early acute respiratory distress syndrome and highly responsive to inhaled nitrix oxide, the administration of intravenous almitrine at a concentration of 16 micrograms.kg-1.min-1 induced an additional increase in Pao2. Dose response of nitric oxide was not changed by the administration of almitrine and a plateau effect was observed at inspiratory nitric oxide concentrations of 1.5 ppm.
Topics: Administration, Inhalation; Adult; Almitrine; Critical Care; Dose-Response Relationship, Drug; Drug Therapy, Combination; Hemodynamics; Humans; Infusions, Intravenous; Male; Middle Aged; Nitric Oxide; Positive-Pressure Respiration; Respiration; Respiratory Distress Syndrome; Respiratory System Agents
PubMed: 7486178
DOI: 10.1097/00000542-199511000-00005