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European Journal of Clinical... Mar 2024Brown adipose tissue (BAT) has emerged as a potential therapeutic target for metabolic disorders due to its thermogenic and anti-obesity properties. β3-adrenergic... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Brown adipose tissue (BAT) has emerged as a potential therapeutic target for metabolic disorders due to its thermogenic and anti-obesity properties. β3-adrenergic receptor (β3-AR) agonists have also gained attention as potential agents for BAT activation and metabolic regulation. Mirabegron, a selective β3-AR-agonist used clinically for overactive bladder syndrome, has been explored for its utility in metabolic disorders. However, the controversy surrounding the ability of mirabegron to activate BAT to accelerate metabolism requires further investigation. The aim of this systematic review is to characterize comprehensively the impact of mirabegron on human BAT and its metabolism.
METHODS
We searched PubMed Central, Web of Science, Embase, and Cochrane Library databases for relevant papers published from the date of database inception to March 2023 for systematic reviews and meta-analyses. We extracted data on primary outcome indicators such as BAT volume, BAT activity, body temperature, and resting energy expenditure (REE), as well as secondary outcome indicators such as heart rate (HR), diastolic blood pressure (DBP), systolic blood pressure (SBP), non-esterified fatty acids (NEFA), blood glucose, and blood insulin from relevant studies. For studies that did not provide suitable data for meta-analysis, we used narrative data synthesis. For studies that provided suitable data for meta-analysis, we conducted meta-analysis using RevMan 5.4 software.
RESULTS
We reviewed 10 papers and included 6 in our meta-analysis. Our findings revealed no significant changes in BAT volume (p = 0.72) or blood glucose (p = 0.52) with mirabegron when compared to the placebo or pre-dose population. However, patients showed significant increases in BAT activity (p < 0.01), blood NEFA (p < 0.01), body temperature (p < 0.01), REE (p < 0.01), HR (p < 0.01), DBP (p < 0.01), SBP (p = 0.25), and blood insulin (p < 0.01).
CONCLUSION
Through our meta-analysis of 6 papers, we found that mirabegron has the potential to increase human BAT activity, REE, NEFA content, body temperature, HR, blood pressure, and blood insulin content. These effects may lead to reductions in blood glucose levels in obese/overweight and diabetic patients. Additionally, the activation of BAT by mirabegron could represent a novel approach for treating obesity, diabetes, and cardiovascular disease.
TRIAL REGISTRATION NUMBER AND DATE
CRD42023413446, 04/11/2023.
Topics: Humans; Acetanilides; Adipose Tissue, Brown; Blood Glucose; Diabetes Mellitus; Fatty Acids, Nonesterified; Insulins; Obesity; Thiazoles
PubMed: 38159219
DOI: 10.1007/s00228-023-03614-0 -
Cureus Nov 2023Autonomic responses elicited by myocardial infarction vary depending on the site of injury, but accurate assessment using heart rate variability during the acute phase... (Review)
Review
Autonomic responses elicited by myocardial infarction vary depending on the site of injury, but accurate assessment using heart rate variability during the acute phase is limited. We systematically searched PubMed without language restrictions throughout July 2023. We reviewed studies reporting autonomic indices separately for anterior and inferior infarcts, followed by a meta-analysis of those reporting the standard deviation of the inter-beat interval between normal sinus beats during the initial 24 hours after the onset of symptoms. Six studies were included, comprising 341 patients (165 anterior, 176 inferior infarcts), all with satisfactory scores on the Newcastle-Ottawa quality scale. The estimated average of the standardized mean difference (based on the random-effects model) was -0.722 (95% confidence intervals: -0.943 to -0.501), which differed from zero (z=-6.416, p<0.0001). This finding indicates sympathetic and vagal dominance during acute anterior and inferior infarcts, respectively, with excessive responses likely contributing to early arrhythmogenesis. Despite the amelioration of autonomic dysfunction by revascularization, infarct location should be considered when commencing β-adrenergic receptor blockade, especially after delayed procedures.
PubMed: 38106761
DOI: 10.7759/cureus.48893 -
The Cochrane Database of Systematic... Dec 2023Management of chronic obstructive pulmonary disease (COPD) commonly involves a combination of long-acting bronchodilators including beta2-agonists (LABA) and muscarinic... (Review)
Review
BACKGROUND
Management of chronic obstructive pulmonary disease (COPD) commonly involves a combination of long-acting bronchodilators including beta2-agonists (LABA) and muscarinic antagonists (LAMA). LABA and LAMA bronchodilators are now available in single-combination inhalers. In individuals with persistent symptoms or frequent exacerbations, inhaled corticosteroids (ICS) are also used with combination LABA and LAMA inhalers. However, the benefits and risks of adding ICS to combination LABA/LAMA inhalers as a triple therapy remain unclear.
OBJECTIVES
To assess the effects of adding an ICS to combination LABA/LAMA inhalers for the treatment of stable COPD.
SEARCH METHODS
We searched the Cochrane Airways Group Register of Trials, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Embase up to 30 November 2022. We also searched ClinicalTrials.gov and the WHO ICTRP up to 30 November 2022.
SELECTION CRITERIA
We included parallel-group randomised controlled trials of three weeks' duration or longer that compared the treatment of stable COPD with ICS in addition to combination LABA/LAMA inhalers against combination LABA/LAMA inhalers alone.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methodological procedures. The primary outcomes were acute exacerbations of COPD, respiratory health-related quality of life, pneumonia and other serious adverse events. The secondary outcomes were symptom scores, lung function, physical capacity, and mortality. We used GRADE to assess certainty of evidence for studies that contributed data to our prespecified outcomes.
MAIN RESULTS
Four studies with a total of 15,412 participants met the inclusion criteria. The mean age of study participants ranged from 64.4 to 65.3 years; the proportion of female participants ranged from 28% to 40%. Most participants had symptomatic COPD (COPD Assessment Test Score ≥ 10) with severe to very severe airflow limitation (forced expiratory volume in one second (FEV1) < 50% predicted) and one or more moderate-to-severe COPD exacerbations in the last 12 months. Trial medications differed amongst studies. The duration of follow-up was 52 weeks in three studies and 24 weeks in one study. We assessed the risk of selection, performance, and detection bias to be low in the included studies; one study was at high risk of attrition bias, and one study was at high risk of reporting bias. Triple therapy may reduce rates of moderate-to-severe COPD exacerbations compared to combination LABA/LAMA inhalers (rate ratio (RR) 0.74, 95% confidence interval (CI) 0.67 to 0.81; n = 15,397; low-certainty evidence). Subgroup analysis stratifying by blood eosinophil counts showed there may be a greater reduction in rate of moderate-to-severe COPD exacerbations with triple therapy in participants with high-eosinophils (RR 0.67, 95% CI 0.60 to 0.75) compared to low-eosinophils (RR 0.87, 95% CI 0.81 to 0.93) (test for subgroup differences: P < 0.01) (high/low cut-offs: 150 eosinophils/µL in three studies; 200 eosinophils/µL in one study). However, moderate-to-substantial heterogeneity was observed in both high- and low-eosinophil subgroups. These subgroup analyses are observational by nature and thus results should be interpreted with caution. Triple therapy may be associated with reduced rates of severe COPD exacerbations (RR 0.75, 95% CI 0.67 to 0.84; n = 14,131; low-certainty evidence). Triple therapy improved health-related quality of life assessed using the St George's Respiratory Questionnaire (SGRQ) by the minimal clinically important difference (MCID) threshold (4-point decrease) (35.3% versus 42.4%, odds ratio (OR) 1.35, 95% CI 1.26 to 1.45; n = 14,070; high-certainty evidence). Triple therapy may result in fewer symptoms measured using the Transition Dyspnoea Index (TDI) (OR 1.33, 95% CI 1.13 to 1.57; n = 3044; moderate-certainty evidence) and improved lung function as measured by change in trough FEV1 (mean difference 38.68 mL, 95% CI 22.58 to 54.77; n = 11,352; low-certainty evidence). However, these benefits fell below MCID thresholds for TDI (1-unit decrease) and trough FEV1 (100 mL), respectively. Triple therapy is probably associated with a higher risk of pneumonia as a serious adverse event compared to combination LABA/LAMA inhalers (3.3% versus 1.9%, OR 1.74, 95% CI 1.39 to 2.18; n = 15,412; moderate-certainty evidence). In contrast, all-cause serious adverse events may be similar between groups (19.7% versus 19.7%, OR 0.95, 95% CI 0.87 to 1.03; n = 15,412; low-certainty evidence). All-cause mortality may be lower with triple therapy (1.4% versus 2.0%, OR 0.70, 95% CI 0.54 to 0.90; n = 15,397; low-certainty evidence).
AUTHORS' CONCLUSIONS
The available evidence suggests that triple therapy may reduce rates of COPD exacerbations (low-certainty evidence) and results in an improvement in health-related quality of life (high-certainty evidence) compared to combination LABA/LAMA inhalers, but probably confers an increased pneumonia risk as a serious adverse event (moderate-certainty evidence). Triple therapy probably improves respiratory symptoms and may improve lung function (moderate- and low-certainty evidence, respectively); however, these benefits do not appear to be clinically significant. Triple therapy may reduce the risk of all-cause mortality compared to combination LABA/LAMA inhalers (low-certainty evidence). The certainty of the evidence was downgraded most frequently for inconsistency or indirectness. Across the four included studies, there were important differences in inclusion criteria, trial medications, and duration of follow-up. Investigation of heterogeneity was limited due to the small number of included studies. We found limited data on the effects of triple therapy compared to combination LABA/LAMA inhalers in patients with mild-moderate COPD and those without a recent exacerbation history.
Topics: Humans; Female; Middle Aged; Aged; Muscarinic Antagonists; Bronchodilator Agents; Adrenergic beta-2 Receptor Agonists; Quality of Life; Pulmonary Disease, Chronic Obstructive; Adrenal Cortex Hormones; Dyspnea; Pneumonia; Disease Progression
PubMed: 38054551
DOI: 10.1002/14651858.CD011600.pub3 -
Archivos de Bronconeumologia Jan 2024
Comparative Study
Efficacy and Safety of Single-inhaler Triple Therapy Containing Dual Bronchodilator With Corticosteroids Compared to Monotherapy, Dual Therapy, or Open Triple Therapy in Moderate/Severe COPD: A Systematic Literature Review.
Topics: Humans; Administration, Inhalation; Adrenal Cortex Hormones; Adrenergic beta-2 Receptor Agonists; Bronchodilator Agents; Drug Therapy, Combination; Muscarinic Antagonists; Nebulizers and Vaporizers; Pulmonary Disease, Chronic Obstructive; Treatment Outcome
PubMed: 37985278
DOI: 10.1016/j.arbres.2023.10.006 -
Arerugi = [Allergy] 2023Long-acting beta2-agonists (LABA) are preferred add-on treatment for adult asthmatic patients whose symptoms cannot be controlled with inhaled corticosteroids (ICS)...
[CQ IN THE LONG-TERM MANAGEMENT OF ADULT ASTHMATIC PATIENTS WHO ARE NOT ADEQUATELY CONTROLLED WITH INHALED CORTICOSTEROIDS MONOTHERAPY, WHICH IS MORE BENEFICIAL: ADDING A LONG ACTING BETA2 AGONIST OR A LONG ACTING MUSCARINIC ANTAGONIST?].
Long-acting beta2-agonists (LABA) are preferred add-on treatment for adult asthmatic patients whose symptoms cannot be controlled with inhaled corticosteroids (ICS) alone. However, over the last decade, long-acting muscarinic antagonists (LAMA) have gained approval for use in treating asthma, and their efficacy is anticipated. Therefore, we conducted a systematic review to investigate whether the addition of LABA or LAMA is more beneficial for the long-term management of adult asthmatic patients poorly controlled on ICS monotherapy. We extracted eight relevant randomized controlled trials (represented in 18 articles) conducted by June 2022 form the corresponding Cochrane review and additional searches through medical databases (CINAHL, Cochrane Library, EMBASE, MEDLINE, PsycINFO, and ICHUSHI (https://www.jamas.or.jp/)). While the LAMA add-on group showed a significantly better improvement in some respiratory function tests, the difference between groups did not exceed the minimum clinically important difference (MCID). On the other hand, the Asthma Quality of Life Questionnaire, a quality of life metric, was significantly higher in the LABA add-on group, but the difference also did not surpass the MCID. Because no outcomes exceeded the MCID, we could not determine whether adding LABA or LAMA on ICS is more beneficial in the long-term management of adult asthmatic patients. Given that no significant differences were found in the incidence of adverse events (including serious ones), when specific adverse events associated with one treatment occur, switching to the other treatment (from LABA to LAMA, or vice versa) can be considered as an option.
Topics: Humans; Adult; Muscarinic Antagonists; Quality of Life; Drug Therapy, Combination; Administration, Inhalation; Asthma; Adrenal Cortex Hormones; World Health Organization; Adrenergic beta-2 Receptor Agonists; Pulmonary Disease, Chronic Obstructive
PubMed: 37967963
DOI: 10.15036/arerugi.72.1158 -
Human Psychopharmacology Nov 2023Oedema associated with psychotropics can impose a considerable burden, leading to increased morbidity and cost. Peripheral oedema is sometimes related to the use of... (Review)
Review
BACKGROUND
Oedema associated with psychotropics can impose a considerable burden, leading to increased morbidity and cost. Peripheral oedema is sometimes related to the use of antidepressants, which are among the most prescribed psychotropic medications. We reviewed the reported cases of antidepressant-associated oedema to understand the risk factors, aetiology and outcome.
METHODS
We searched the Medline, Web of Science and Embase databases to identify reported cases of peripheral oedema associated with antidepressant use. We included studies published in English and those with full-text availability. A systematic review of the reports was done to identify the antidepressants associated with oedema, explore possible risk factors, investigate potential mechanisms, and assess the outcome.
RESULTS
We identified a total of 45 cases (27 case reports and five case series) that reported oedema associated with antidepressant use. Almost all major classes of antidepressants were found to be associated with oedema. Among these drugs, trazodone, mirtazapine, and escitalopram were the most implicated. Older age and female gender were more commonly associated with oedema. Etiologically, antagonism of α adrenergic receptors and 5HT receptors, leading to vasodilation and oedema, emerged as the most prevalent mechanisms. In most cases, the oedema subsided following the discontinuation of the antidepressants.
CONCLUSIONS
Peripheral oedema associated with antidepressant use can represent a significant adverse drug reaction involving various classes of antidepressants. To ensure timely identification and proper management of oedema, regular monitoring is crucial.
Topics: Humans; Female; Antidepressive Agents; Mirtazapine; Risk Factors; Edema
PubMed: 37941526
DOI: 10.1002/hup.2884 -
Paediatric Anaesthesia Feb 2024During scoliosis surgery, motor evoked potentials (MEP), and somatosensory evoked potentials (SSEP) have been reported to be affected by the use of higher doses of... (Review)
Review
BACKGROUND
During scoliosis surgery, motor evoked potentials (MEP), and somatosensory evoked potentials (SSEP) have been reported to be affected by the use of higher doses of anesthetic agents. Dexmedetomidine, a sympatholytic agent, an alpha-2 receptor agonist, has been used as an adjunctive agent to lower anesthetic dose. However, there is conflicting evidence regarding the effects of dexmedetomidine on the intraoperative neurophysiological monitoring of MEP and SSEP during surgery, particularly among pediatric patients.
OBJECTIVES
This systematic review aimed to determine whether, during spinal fusion surgery in pediatric patients with scoliosis, dexmedetomidine alters MEP amplitude or SSEP latency and amplitude and, if so, whether different doses of dexmedetomidine display different effects (PROSPERO registration number CRD42022300562).
METHODS
We searched PubMed, Scopus, and Cochrane Library on January 1, 2022 and included randomized controlled trials, observational cohort and case-control studies and case series investigating dexmedetomidine in the population of interest and comparing against a standardized anesthesia regimen without dexmedetomidine or comparing multiple doses of dexmedetomidine. Animal and in vitro studies and conference abstracts were excluded.
RESULTS
We found substantial heterogeneity in the risk of bias (per Cochrane-preferred tools) of the included articles (n = 5); results are summarized without meta-analysis. Articles with the lowest risk of bias indicated that dexmedetomidine was associated with MEP loss and that higher doses of dexmedetomidine increased risk. In contrast, articles reporting no association between dexmedetomidine and MEP loss suffered from higher risk of bias, including suspected or confirmed problems with confounding, outcome measurement, participant selection, results reporting, and lack of statistical transparency and power.
CONCLUSION
Given the limitations of the studies available in the literature, it would be advisable to conduct rigorous randomized controlled trials with larger sample sizes to assess the effects of dexmedetomidine use of in scoliosis surgery in pediatric patients.
Topics: Humans; Child; Intraoperative Neurophysiological Monitoring; Dexmedetomidine; Scoliosis; Evoked Potentials, Somatosensory; Evoked Potentials, Motor; Adrenergic alpha-2 Receptor Agonists; Retrospective Studies
PubMed: 37927199
DOI: 10.1111/pan.14795 -
Journal of Perinatology : Official... Feb 2024Opioids and benzodiazepines have historically been employed for pain relief; however, they are associated with detrimental long-term neurodevelopmental consequences.... (Review)
Review
Opioids and benzodiazepines have historically been employed for pain relief; however, they are associated with detrimental long-term neurodevelopmental consequences. Dexmedetomidine, a highly selective alpha-2-adrenoreceptor agonist, has piqued interest as a viable alternative for neonates, owing to its potential analgesic and neuroprotective attributes. We conducted a systematic review to assess the efficacy and safety of dexmedetomidine utilization in neonates. We conducted a comprehensive search of Ovid, MEDLINE, EMBASE, PubMed, Cochrane, and CINAHL, spanning from January 2010 to September 2022. Our review encompassed six studies involving 252 neonates. Overall, dexmedetomidine may be effective in achieving sedation and analgesia. Furthermore, it may reduce the need for adjunctive sedation or analgesia, shorten the time to extubation, decrease the duration of mechanical ventilation, and accelerate the attainment of full enteral feeds. Notably, no significant adverse effects associated with dexmedetomidine were reported. Nevertheless, additional well-designed studies to establish both the efficacy and safety of dexmedetomidine in neonatal care are needed.
Topics: Infant, Newborn; Humans; Dexmedetomidine; Pain; Adrenergic alpha-2 Receptor Agonists; Pain Management; Analgesia
PubMed: 37845426
DOI: 10.1038/s41372-023-01802-5 -
The Cochrane Database of Systematic... Oct 2023Overactive bladder (OAB) is a common chronic and bothersome condition. Bladder training is widely prescribed as a first-line treatment for OAB, but the efficacy has been... (Review)
Review
BACKGROUND
Overactive bladder (OAB) is a common chronic and bothersome condition. Bladder training is widely prescribed as a first-line treatment for OAB, but the efficacy has been systematically evaluated for urinary incontinence rather than OAB alone.
OBJECTIVES
To evaluate the benefits and harms of bladder training for treating adults with OAB compared to no treatment, anticholinergics, β3-adrenoceptor agonists, or pelvic floor muscle training (PFMT) alone or in combination.
SEARCH METHODS
We used standard, extensive Cochrane search methods. The latest search date was 6 November 2022.
SELECTION CRITERIA
We included randomized controlled trials involving adults aged 18 years or older with non-neurogenic OAB. We excluded studies of participants whose symptoms were caused by factors outside the urinary tract (e.g. neurologic disorders, cognitive impairment, gynecologic diseases).
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. Our primary outcomes were 1. participant-reported cure or improvement, 2. symptom- and condition-related quality of life (QoL), and 3.
ADVERSE EVENTS
Secondary outcomes included 4. participant-reported satisfaction, 5. number of incontinence episodes, 6. number of urgency episodes, and 7. number of micturition episodes. For the purpose of this review, we considered two time points: immediately after the treatment (early phase) and at least two months after the treatment (late phase). We used GRADE to assess certainty of evidence for each outcome.
MAIN RESULTS
We included 15 trials with 2007 participants; participants in these trials were predominantly women (89.3%). We assessed the risk of bias of results for primary and secondary outcomes, which across all studies was similar and predominantly of high risk of bias, and none were at low risk of bias. The certainty of evidence was low to very low, with some moderate, across measured outcomes. Bladder training versus no treatment: three studies involving 92 participants compared bladder training to no treatment. The evidence is very uncertain about the effects of bladder training on cure or improvement at the early phase (risk ratio (RR) 17.00, 95% confidence interval (CI) 1.13 to 256.56; 1 study, 18 participants; very low-certainty evidence). Bladder training may reduce the number of incontinence episodes (mean difference (MD) -1.86, 95% CI -3.47 to -0.25; 1 study, 14 participants; low-certainty evidence). No studies measured symptom- and condition-related QoL, number of adverse events, participant-reported satisfaction, number of urgency episodes, or number of micturition episodes in the early phase. Bladder training versus anticholinergics: seven studies (602 participants) investigated the effects of bladder training versus anticholinergic therapy. Bladder training may be more effective than anticholinergics on cure or improvement at the early phase (RR 1.37, 95% CI 1.10 to 1.70; 4 studies, 258 participants; low-certainty evidence). The evidence is very uncertain about the effects of bladder training on symptom- and condition-related QoL (standardized mean difference (SMD) -0.06, 95% CI -0.89 to 0.77; 2 studies, 117 participants; very low-certainty evidence). Although the evidence is very uncertain, there were fewer adverse events in the bladder training group than in the anticholinergics group (RR 0.03, 95% CI 0.01 to 0.17; 3 studies, 187 participants; very low-certainty evidence). The evidence is very uncertain about the effects of the number of incontinence episodes per 24 hours (MD 0.36, 95% CI -0.27 to 1.00; 2 studies, 117 participants; very low-certainty evidence), the number of urgency episodes per 24 hours (MD 0.70, 95% CI -0.62 to 2.02; 2 studies, 92 participants; very low-certainty evidence), and the number of micturition episodes per 24 hours (MD -0.35, 95% CI -1.90 to 1.20; 3 studies, 175 participants; very low-certainty evidence). No studies measured participant-reported satisfaction in the early phase. Bladder training versus PFMT: three studies involving 203 participants compared bladder training to PFMT. The evidence is very uncertain about the different effects between bladder training and PFMT on symptom- and condition-related QoL at the early phase (SMD 0.10, 95% CI -0.19 to 0.40; 2 studies, 178 participants; very low-certainty evidence). There were no adverse events in either group at the early phase (1 study, 97 participants; moderate-certainty evidence). The evidence is uncertain about the effects of the number of incontinence episodes per 24 hours (MD 0.02, 95% CI -0.35 to 0.39, 1 study, 81 participants; low-certainty evidence) and very uncertain about the number of micturition episodes per 24 hours (MD 0.10, 95% CI -1.44 to 1.64; 1 study, 81 participants; very low-certainty evidence). No studies measured cure or improvement, participant-reported satisfaction, or number of urgency episodes in the early phase. Although we were interested in studies examining bladder training versus β3-adrenoceptor agonists, in combination with β3-adrenoceptor agonists versus β3-adrenoceptor agonists alone, and in combination with PFMT versus PFMT alone, we did not identify any eligible studies for these comparisons.
AUTHORS' CONCLUSIONS
This review focused on the effect of bladder training to treat OAB. However, most of the evidence was low or very-low certainty. Based on the low- or very low-certainty evidence, bladder training may cure or improve OAB compared to no treatment. Bladder training may be more effective to cure or improve OAB than anticholinergics, and there may be fewer adverse events. There may be no difference in efficacy or safety between bladder training and PFMT. More well-designed trials are needed to reach a firm conclusion.
Topics: Female; Adult; Humans; Male; Urinary Bladder, Overactive; Quality of Life; Electric Stimulation Therapy; Urinary Bladder; Pelvic Floor; Urinary Incontinence; Cholinergic Antagonists; Receptors, Adrenergic
PubMed: 37811598
DOI: 10.1002/14651858.CD013571.pub2 -
European Journal of Pharmacology Nov 2023Intestinal ischemia/reperfusion injury (IRI) is a multifactorial, complex pathophysiological process in clinical settings. In recent years, intestinal IRI has received... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Intestinal ischemia/reperfusion injury (IRI) is a multifactorial, complex pathophysiological process in clinical settings. In recent years, intestinal IRI has received increasing attention due to increased morbidity and mortality. To date, there are no effective treatments. Dexmedetomidine (DEX), a highly selective α-adrenergic receptor agonist, has been demonstrated to be effective against intestinal IRI. In this systematic review and meta-analysis, we evaluated the efficacy and potential mechanisms of DEX as a treatment for intestinal IRI in animal models.
METHODS
Five databases (PubMed, Embase, Web of Science, Cochrane Library, and Scopus) were searched until March 15, 2023. Using the SYRCLE risk bias tool, we assessed methodological quality. Statistical analysis was conducted using STATA 12 and R 4.2.2. We analyzed the related outcomes (mucosa damage-related indicators; inflammation-relevant markers, oxidative stress markers) relied on the fixed or random-effects models.
RESULTS
There were 15 articles including 18 studies included, and 309 animals were involved in the studies. Compared to the model groups, DEX improved intestinal IRI. DEX decreased Chiu's score and serum diamine oxidase (DAO) level. DEX reduced the level of inflammation-relevant markers (interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α). DEX also improved oxidative stress (decreased malondialdehyde (MDA), increased superoxide dismutase (SOD)).
CONCLUSIONS
DEX's effectiveness in ameliorating intestinal IRI has been demonstrated in animal models. Antioxidation, anti-inflammation, anti-apoptotic, anti-pyroptosis, anti-ferroptosis, enhancing mitophagy, reshaping the gut microbiota, and gut barrier protection are possible mechanisms. However, in light of the heterogeneity and methodological quality of these studies, further well-designed preclinical studies are warranted before clinical implication.
Topics: Rats; Animals; Dexmedetomidine; Rats, Sprague-Dawley; Adrenergic alpha-2 Receptor Agonists; Reperfusion Injury; Inflammation; Ischemia
PubMed: 37778612
DOI: 10.1016/j.ejphar.2023.176090