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Nature Communications Apr 2017The β1-adrenergic-receptor (ADRB1) antagonist metoprolol reduces infarct size in acute myocardial infarction (AMI) patients. The prevailing view has been that...
The β1-adrenergic-receptor (ADRB1) antagonist metoprolol reduces infarct size in acute myocardial infarction (AMI) patients. The prevailing view has been that metoprolol acts mainly on cardiomyocytes. Here, we demonstrate that metoprolol reduces reperfusion injury by targeting the haematopoietic compartment. Metoprolol inhibits neutrophil migration in an ADRB1-dependent manner. Metoprolol acts during early phases of neutrophil recruitment by impairing structural and functional rearrangements needed for productive engagement of circulating platelets, resulting in erratic intravascular dynamics and blunted inflammation. Depletion of neutrophils, ablation of Adrb1 in haematopoietic cells, or blockade of PSGL-1, the receptor involved in neutrophil-platelet interactions, fully abrogated metoprolol's infarct-limiting effects. The association between neutrophil count and microvascular obstruction is abolished in metoprolol-treated AMI patients. Metoprolol inhibits neutrophil-platelet interactions in AMI patients by targeting neutrophils. Identification of the relevant role of ADRB1 in haematopoietic cells during acute injury and the protective role upon its modulation offers potential for developing new therapeutic strategies.
Topics: Adrenergic beta-1 Receptor Antagonists; Animals; Cell Movement; Hematopoietic Stem Cells; Humans; Metoprolol; Mice; Myocardial Infarction; Myocardial Reperfusion Injury; Neutrophils; Platelet Aggregation; RNA, Messenger; Receptors, Adrenergic, beta-1
PubMed: 28416795
DOI: 10.1038/ncomms14780 -
The Cochrane Database of Systematic... Jan 2015People undergoing major vascular surgery have an increased risk of postoperative cardiac complications. Beta-adrenergic blockers represent an important and established... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
People undergoing major vascular surgery have an increased risk of postoperative cardiac complications. Beta-adrenergic blockers represent an important and established pharmacological intervention in the prevention of cardiac complications in people with coronary artery disease. It has been proposed that this class of drugs may reduce the risk of perioperative cardiac complications in people undergoing major non-cardiac vascular surgery.
OBJECTIVES
To review the efficacy and safety of perioperative beta-adrenergic blockade in reducing cardiac or all-cause mortality, myocardial infarction, and other cardiovascular safety outcomes in people undergoing major non-cardiac vascular surgery.
SEARCH METHODS
The Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (January 2014) and the Cochrane Central Register of Controlled Trials (CENTRAL; 2013, Issue 12). We searched trials databases and checked reference lists of relevant articles.
SELECTION CRITERIA
We included prospective, randomised controlled trials of perioperative beta-adrenergic blockade of people over 18 years of age undergoing non-cardiac vascular surgery.
DATA COLLECTION AND ANALYSIS
Two review authors independently performed study selection and data extraction. We resolved disagreements through discussion. We performed meta-analysis using a fixed-effect model with odds ratios (ORs) and 95% confidence intervals (CIs).
MAIN RESULTS
We included two studies in this review, both of which were double-blind, randomised controlled trials comparing perioperative beta-adrenergic blockade (metoprolol) with placebo, on cardiovascular outcomes in people undergoing major non-cardiac vascular surgery. We included 599 participants receiving beta-adrenergic blockers (301 participants) or placebo (298 participants). The overall quality of studies was good. However, one study did not report random sequence generation or allocation concealment techniques, indicating possible selection bias, and the other study did not report outcome assessor blinding and was possibly underpowered. It should be noted that several of the outcomes were only reported in a single study and neither of the studies reported on vascular patency/graft occlusion, which reduces the quality of evidence to moderate. There was no evidence that perioperative beta-adrenergic blockade reduced all-cause mortality (OR 0.62, 95% CI 0.03 to 15.02), cardiovascular mortality (OR 0.34, 95% CI 0.01 to 8.32), non-fatal myocardial infarction (OR 0.83, 95% CI 0.46 to 1.49; P value = 0.53), arrhythmia (OR 0.70, 95% CI 0.26 to 1.88), heart failure (OR 1.71, 95% CI 0.40 to 7.23), stroke (OR 2.67, 95% CI 0.11 to 67.08), composite cardiovascular events (OR 0.87, 95% CI 0.55 to 1.39; P value = 0.57) or re-hospitalisation at 30 days (OR 0.86, 95% CI 0.48 to 1.52). However, there was strong evidence that beta-adrenergic blockers increased the odds of intra-operative bradycardia (OR 4.97, 95% CI 3.22 to 7.65; P value < 0.00001) and intra-operative hypotension (OR 1.84, 95% CI 1.31 to 2.59; P value = 0.0005).
AUTHORS' CONCLUSIONS
This meta-analysis currently offers no clear evidence that perioperative beta-adrenergic blockade reduces postoperative cardiac morbidity and mortality in people undergoing major non-cardiac vascular surgery. There is evidence that intra-operative bradycardia and hypotension are more likely in people taking perioperative beta-adrenergic blockers, which should be weighed with any benefit.
Topics: Administration, Oral; Adrenergic beta-Antagonists; Adult; Cardiovascular Diseases; Cause of Death; Humans; Injections, Intravenous; Metoprolol; Postoperative Complications; Randomized Controlled Trials as Topic; Risk Reduction Behavior; Vascular Surgical Procedures
PubMed: 25879091
DOI: 10.1002/14651858.CD006342.pub2 -
Acta Poloniae Pharmaceutica 2006A procedure for simultaneous determination of metoprolol and hydrochlorothiazide in tablets by employing derivative spectrophotometry, "zero-crossing" method was...
A procedure for simultaneous determination of metoprolol and hydrochlorothiazide in tablets by employing derivative spectrophotometry, "zero-crossing" method was developed. The third order derivative absorption spectra at lambda approximately 281 nm were used for metoprolol and the first order derivative spectra at lambda approximately 282 nm were used for hydrochlorothiazide. No interferences were found between both determined constituents and those of matrix. A good accuracy and precision of simultaneous determination of metoprolol and hydrochlorothiazide were confirmed by statistical analysis. The recovery of individual constituents under established conditions is very high and ranges from 98.79% to 99.39%. Linearity is maintained within a wide concentration range from 100.0 microg mL(-1) to 300.0 microg mL(-1) and from 12.5 microg mL(-1) to 37.5 microg mL(-1) for metoprolol and hydrochlorothiazide, respectively. The detection limit is 5.0 microg mL(-1) for metoprolol and 1.5 microg mL(-1) for hydrochlorothiazide. The corresponding quantitation limits are 15.0 microg mL(-1) for metoprolol and 4.5 microg mL(-1) for hydrochlorothiazide.
Topics: Hydrochlorothiazide; Metoprolol; Signal Processing, Computer-Assisted; Spectrophotometry, Ultraviolet; Technology, Pharmaceutical
PubMed: 20085220
DOI: No ID Found -
Acta Pharmacologica Sinica May 2020Obstructive sleep apnea (OSA) is closely associated with central nervous system diseases and could lead to autonomic nerve dysfunction, which is often seen in...
Obstructive sleep apnea (OSA) is closely associated with central nervous system diseases and could lead to autonomic nerve dysfunction, which is often seen in neurodegenerative diseases. Previous studies have shown that metoprolol prevents several chronic OSA-induced cardiovascular diseases through inhibiting autonomic nerve hyperactivity. It remains unclear whether chronic OSA can lead to dendritic remodeling in the brain, and whether metoprolol affects the dendritic remodeling. In this study we investigated the effect of metoprolol on dendrite morphology in a canine model of chronic OSA, which was established in beagles through clamping and reopening the endotracheal tube for 4 h every other day for 12 weeks. OSA beagles were administered metoprolol (5 mg· kg· d). The dendritic number, length, crossings and spine density of neurons in hippocampi and prefrontal cortices were assessed by Golgi staining. And the protein levels of hypoxia-inducible factor-1α (HIF-1α) and brain-derived neurotrophic factor (BDNF) were measured by Western blotting. We showed that chronic OSA successfully induced significant brain hypoxia evidenced by increased HIF-1α levels in CA1 region and dentate gyrus of hippocampi, as well as in prefrontal cortex. Furthermore, OSA led to markedly decreased dendrite number, length and intersections, spine loss as well as reduced BDNF levels. Administration of metoprolol effectively prevented the dendritic remodeling and spine loss induced by chronic OSA. In addition, administration of metoprolol reversed the decreased BDNF, which might be associated with the metoprolol-induced neuronal protection. In conclusion, metoprolol protects against neuronal dendritic remodeling in hippocampi and prefrontal cortices induced by chronic OSA in canine.
Topics: Animals; Chronic Disease; Dendrites; Disease Models, Animal; Dogs; Dose-Response Relationship, Drug; Male; Metoprolol; Neurons; Sleep Apnea, Obstructive
PubMed: 31863057
DOI: 10.1038/s41401-019-0323-8 -
Water Research May 2011Electrochemical oxidation has been proposed for the elimination of pesticides, pharmaceuticals and other organic micropollutants from complex waste streams. However, the...
Electrochemical oxidation has been proposed for the elimination of pesticides, pharmaceuticals and other organic micropollutants from complex waste streams. However, the detrimental effect of halide ion mediators and the generation of halogenated by-products in this process have largely been neglected thus far. In this study, we investigated the electrochemical oxidation pathways of the β-blocker metoprolol in reverse osmosis concentrate (ROC) from a water reclamation plant using titanium anodes coated with Ru(0.7)Ir(0.3)O(2) or SnO(2)-Sb metal oxide layers. The results of liquid chromatography-mass spectrometry analysis indicated that irrespective of the electrode coating the same oxidant species participated in electrochemical transformation of metoprolol in ROC. Although Ti/SnO(2)-Sb exhibited higher oxidizing power for the same applied specific electrical charge, the generation of large fractions of chloro-, chloro-bromo- and bromo derivatives was observed for both electrode coatings. However, degradation rates of metoprolol and its degradation products were generally higher for the Ti/SnO(2)-Sb anode. Chemical analyses of metoprolol and its by-products were complemented with bioanalytical tools in order to investigate their toxicity relative to the parent compound. Results of the bioluminescence inhibition test with Vibrio fischeri and the combined algae test with Pseudokirchneriella subcapitata indicated a substantial increase in non-specific toxicity of the reaction mixture due to the formed halogenated by-products, while the specific toxicity (inhibition of photosynthesis) remained unchanged.
Topics: Adrenergic beta-Antagonists; Aliivibrio fischeri; Antimony; Biological Assay; Electricity; Electrochemical Techniques; Electrodes; Iridium; Metals, Heavy; Metoprolol; Osmosis; Oxidation-Reduction; Ruthenium; Spectrometry, Mass, Electrospray Ionization; Tin Compounds; Titanium
PubMed: 21496862
DOI: 10.1016/j.watres.2011.03.040 -
Computational and Mathematical Methods... 2022To investigate the effects of metoprolol succinate combined with Entresto (Sacubitril Valsartan Sodium Tablets) on cardiac function and coagulation function in patients...
OBJECTIVE
To investigate the effects of metoprolol succinate combined with Entresto (Sacubitril Valsartan Sodium Tablets) on cardiac function and coagulation function in patients with congestive heart failure (CHF).
METHODS
About 120 patients with CHF treated from April 2018 to April 2021 were enrolled in our hospital. The patients were arbitrarily assigned into control group and study group. The control group was cured with metoprolol succinate sustained-release tablets, and the study group was cured with metoprolol succinate sustained-release tablets combined with Entresto. The curative effect, cardiac function, vascular endothelial function, oxidative stress, and coagulation function were compared.
RESULTS
First of all, we compared the general data, and there exhibited no difference in age, sex, course of disease, hypertension, coronary heart disease, diabetes, atrial fibrillation, and other general data ( > 0.05). Second, we compared the clinical efficacy. The effective rate of the study group (98.33%) was higher (90.00%) ( < 0.05). There exhibited no significant difference in cardiac function indexes before treatment, but after treatment, LVEF increased, LVESD and LVEDD decreased, LVESD and LVEDD in the study group were lower, and LVEF in the study group was higher ( < 0.05). Before treatment, there exhibited no significant difference in vascular endothelial function. However, the levels of CGRP and ET increased and the level of NO decreased, and the level of NO in the study group was lower, while the levels of CGRP and ET in the study group were higher after treatment ( < 0.05). There exhibited no significant difference in oxidative stress indexes before treatment, however, the levels of GSH-Px and SOD increased and the levels of MDA decreased after treatment, while the level of MDA in the study group was lower, while the levels of GSH-Px and SOD in the study group were higher ( < 0.05). Finally, we compared the indexes of blood coagulation function. There exhibited no significant difference before treatment, but after treatment, the levels of APTT, PT, and FIB decreased, and the levels of APTT, PT, and FIB in the study group were lower ( < 0.05).
CONCLUSION
Clinical practice demonstrated that LVESD and LVEDD decreased and LVEF increased after treatment with Entresto combined with metoprolol in CHF patients, which can effectively facilitate cardiac function and vascular endothelial function, reduce oxidative stress reaction, and improve blood coagulation indexes, suggesting that Entresto combined with metoprolol can improve ventricular remodeling with good safety.
Topics: Aminobutyrates; Biphenyl Compounds; Blood Coagulation; Calcitonin Gene-Related Peptide; Delayed-Action Preparations; Drug Combinations; Heart Failure; Humans; Metoprolol; Superoxide Dismutase; Valsartan
PubMed: 35637842
DOI: 10.1155/2022/9765884 -
Canadian Association of Radiologists... Feb 2022Intravenous [IV] esmolol, an alternative to IV metoprolol for coronary computed tomography angiography [CCTA], has shorter half-life that decreases the risk of prolonged... (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
Intravenous [IV] esmolol, an alternative to IV metoprolol for coronary computed tomography angiography [CCTA], has shorter half-life that decreases the risk of prolonged hypotension. The primary aim was to prospectively compare IV esmolol alone to IV metoprolol alone for effectiveness in achieving heart rate [HR] of 60 beats per minute[bpm] during CCTA. The secondary aim was to compare hemodynamic response, image quality, radiation dose and cost.
MATERIALS AND METHODS
Institutional Review Board approved prospective randomized study of 28 CCTA patients medicated in a 1:1 blinded match with IV esmolol or IV metoprolol to achieve HR of 60 bpm. Serial hemodynamic response was measured at 6 specified times. Two cardiac radiologists independently scored the image quality.
RESULTS
Both IV esmolol and IV metoprolol achieved the target HR. IV esmolol resulted in significantly less profound and shorter duration of reduction in systolic blood pressure [BP] than IV metoprolol with a difference of -10, -14 and -9 mm Hg compared to -20, -26 and -25 mmHg at 2, 15 & 30 min respectively. No significant difference in HR at image acquisition, exposure window, radiation dose and image quality. Although IV esmolol was expensive, the overall cost of care was comparable to IV metoprolol due to shortened post CCTA observation period consequent to faster restoration of hemodynamic status.
CONCLUSION
Comparison of IV esmolol and IV metoprolol demonstrate that both are effective in achieving the target HR but significantly faster recovery of HR and BP in patients who receive IV esmolol was found.
Topics: Administration, Intravenous; Adrenergic beta-1 Receptor Antagonists; Computed Tomography Angiography; Coronary Angiography; Coronary Artery Disease; Cost-Benefit Analysis; Female; Heart Rate; Hemodynamics; Humans; Male; Metoprolol; Middle Aged; Propanolamines; Prospective Studies; Single-Blind Method
PubMed: 34293933
DOI: 10.1177/08465371211023947 -
Journal of the American Heart... Sep 2021Background Carvedilol may have favorable glycemic properties compared with metoprolol, but it is unknown if carvedilol has mortality benefit over metoprolol in patients...
Background Carvedilol may have favorable glycemic properties compared with metoprolol, but it is unknown if carvedilol has mortality benefit over metoprolol in patients with type 2 diabetes (T2D) and heart failure with reduced ejection fraction (HFrEF). Methods and Results Using Danish nationwide databases between 2010 and 2018, we followed patients with new-onset HFrEF treated with either carvedilol or metoprolol for all-cause mortality until the end of 2018. Follow-up started 120 days after initial HFrEF diagnosis to allow initiation of guideline-directed medical therapy. There were 39 260 patients on carvedilol or metoprolol at baseline (mean age 70.8 years, 35% women), of which 9355 (24%) had T2D. Carvedilol was used in 2989 (32%) patients with T2D and 10 411 (35%) of patients without T2D. Users of carvedilol had a lower prevalence of atrial fibrillation (20% versus 35%), but other characteristics appeared well-balanced between the groups. Totally 11 306 (29%) were deceased by the end of follow-up. We observed no mortality differences between carvedilol and metoprolol, multivariable-adjusted hazard ratio (HR) 0.97 (0.90-1.05) in patients with T2D versus 1.00 (0.95-1.05) for those without T2D, for difference =0.99. Rates of new-onset T2D were lower in users of carvedilol versus metoprolol; age, sex, and calendar year adjusted HR 0.83 (0.75-0.91), <0.0001. Conclusions In a contemporary clinical cohort of HFrEF patients with and without T2D, carvedilol was not associated with a reduction in long-term mortality compared with metoprolol. However, carvedilol was associated with lowered risk of new-onset T2D supporting the assertion that carvedilol has a more favorable metabolic profile than metoprolol.
Topics: Aged; Carvedilol; Denmark; Diabetes Mellitus, Type 2; Female; Heart Failure; Humans; Male; Metoprolol; Retrospective Studies; Stroke Volume
PubMed: 34533058
DOI: 10.1161/JAHA.121.021310 -
British Journal of Pharmacology Mar 19901. The beta-adrenoceptor affinity and blocking potency of the two enantiomers and the racemate of metoprolol were investigated in vitro, by use of a receptor-binding...
1. The beta-adrenoceptor affinity and blocking potency of the two enantiomers and the racemate of metoprolol were investigated in vitro, by use of a receptor-binding technique, and in vivo in the anaesthetized cat. 2. The enantiomeric purity of the S- and R-form was: greater than 99.2% and greater than 99.9%, respectively. 3. The beta 1- and beta 2-adrenoceptor affinity (-log equilibrium dissociation constant) of the enantiomers was determined from competition binding experiments (radioligand: [125I]-(S)-pindolol) performed in membranes prepared from the guinea-pig left ventricular free wall (predominantly beta 1) and soleus muscle (beta 2). The beta 1-adrenoceptor affinity was (means +/- s.d.): 7.73 +/- 0.10 and 5.00 +/- 0.06 for the S- and R-form of metoprolol, respectively. The corresponding values for beta 2-adrenoceptors were 6.28 +/- 0.06 (S) and 4.52 +/- 0.09 (R). Thus, the difference in affinity for the two enantiomers was greater on beta 1- (about 500) than on beta 2-adrenoceptors (about 50). The beta 1-adrenoceptor selectivity of the S-form (about 30) was similar to that of the racemic metoprolol, while the R-form was almost non-selective (3 fold beta 1-selective). 4. In the anaesthetized cat, the (-log) intravenous doses (mumol kg-1) of S- and R-metoprolol causing a 50% reduction (ED50) in the heart rate response to sympathetic nerve stimulation were determined. The doses inducing a 25% depression (DD25) of the basal myocardial contractility were also estimated. For the two enantiomers, the beta 1-blocking potency (-log ED50) was 7.04 +/- 0.16 (S) and 4.65 +/- 0.16 (R). A significant cardiodepressive effect was observed at high doses (-log DD25): 4.18 + 0.20 (S) and 4.08 + 0.10 (R). 5. It is concluded that the binding of metoprolol to beta 1-adrenoceptors has a stricter steric requirement than that for the binding of this beta l-blocker to beta 2-adrenoceptors. Furthermore, the non-specific cardiodepressive effect of metoprolol was observed at equally high doses for the two enantiomers.
Topics: Adrenergic beta-Antagonists; Anesthesia; Animals; Cats; Depression, Chemical; Guinea Pigs; Heart; In Vitro Techniques; Iodine Radioisotopes; Male; Metoprolol; Receptors, Adrenergic, beta; Stereoisomerism
PubMed: 1970503
DOI: 10.1111/j.1476-5381.1990.tb12974.x -
British Journal of Clinical Pharmacology Mar 19811 Plasma concentrations of metoprolol and a pharmacologically active metabolite, H119/66, have been measured in young and elderly volunteers after a single dose of 100...
1 Plasma concentrations of metoprolol and a pharmacologically active metabolite, H119/66, have been measured in young and elderly volunteers after a single dose of 100 mg metoprolol tartrate and after repeated administrated over a period of 1 week. Whilst concentrations of metoprolol are similar in each group, concentrations of H119/66 are approximately twice as high in the elderly. 2 Concentrations of unchanged metoprolol and of the major, but pharmacologically inactive, metabolite, H117/04, together with the two active metabolites of metoprolol have been determined in urine. Only the excretion of metoprolol was diminished in the elderly. 3 Areas under the plasma concentration curve for metoprolol after repeated administration are greater than would be predicted from single dose data, and possible explanations for this are discussed. Concentrations of the pharmacologically active metabolite, H119/66, remain unaltered during chronic dosing of metoprolol. 4 This study has shown that the effect of age on the pharmacokinetics of metoprolol and its metabolites is less pronounced than that observed for other drugs.
Topics: Adolescent; Adult; Aged; Aging; Chemical Phenomena; Chemistry; Female; Humans; Kinetics; Metoprolol; Middle Aged; Propanolamines
PubMed: 7213530
DOI: 10.1111/j.1365-2125.1981.tb00536.x