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BMC Neuroscience Mar 2018Labor subjects the fetus to an hypoxic episode and concomitant adrenomodullary catecholamine surge that may provide protection against the hypoxic insult. The...
BACKGROUND
Labor subjects the fetus to an hypoxic episode and concomitant adrenomodullary catecholamine surge that may provide protection against the hypoxic insult. The beta1-adrenergic agonist dobutamine protects against hypoxia/aglycemia induced neuronal damage. We aimed to identify the associated protective biological processes involved.
RESULTS
Hippocampal slices from 6 days old mice showed significant changes of gene expression comparing slices with or without dobutamine (50 mM) in the following two experimental paradigms: (1) control conditions versus lipopolysacharide (LPS) stimulation and (2) oxygen-glucose deprivation (OGD), versus combined LPS/OGD. Dobutamine depressed the inflammatory response by modifying the toll-like receptor-4 signalling pathways, including interferon regulatory factors and nuclear factor κ B activation in experimental paradigm 1. The anti-oxidant defense genes superoxide dismutase 3 showed an upregulation in the OGD paradigm while thioredoxin reductase was upregulated in LPS paradigm. The survival genes Bag-3, Tinf2, and TMBIM-1, were up-regulated in paradigm 1. Moreover, increased levels of SOD3 were verified on the protein level 24 h after OGD and control stimulation in cultures with or without preconditioning with LPS and dobutamine, respectively.
CONCLUSIONS
Neuroprotective treatment with dobutamine depresses expression of inflammatory mediators and promotes the defense against oxidative stress and depresses apoptotic genes in a model of neonatal brain hypoxia/ischemia interpreted as pharmacological preconditioning. We conclude that beta1-adrenoceptor activation might be an efficient strategy for identifying novel pharmacological targets for protection of the neonatal brain.
Topics: Animals; Antioxidants; Dobutamine; Gene Expression; Hippocampus; Inflammation; Mice, Inbred BALB C; Neurons; Neuroprotection; Neuroprotective Agents; Oxidants; Oxygen; Superoxide Dismutase; Up-Regulation
PubMed: 29523072
DOI: 10.1186/s12868-018-0415-2 -
American Journal of Veterinary Research May 2021To determine the in vitro effects of epinephrine, norepinephrine, and dobutamine on lipopolysaccharide (LPS)-stimulated production of tumor necrosis factor-α (TNF-α),...
In vitro effects of epinephrine, norepinephrine, and dobutamine on lipopolysaccharide-stimulated production of tumor necrosis factor-α, interleukin-6, and interleukin-10 in blood from healthy dogs.
OBJECTIVE
To determine the in vitro effects of epinephrine, norepinephrine, and dobutamine on lipopolysaccharide (LPS)-stimulated production of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-10 (IL-10) in blood from healthy dogs.
SAMPLES
Blood samples from 9 healthy dogs.
PROCEDURES
Blood samples were incubated with LPS from O127:B8 or PBSS (control) for 1 hour. Afterward, the samples were incubated with 10μM epinephrine, norepinephrine, or dobutamine or with saline (0.9% NaCl) solution (control) for 23 hours. Leukocyte viability was assessed by use of trypan-blue exclusion in blood from 2 dogs to ensure cell viability was not altered by the catecholamines. Tumor necrosis factor-α, IL-6, and IL-10 concentrations were measured in the supernatant in duplicate with a canine-specific multiplex bead-based assay. Blood samples from 2 dogs were used to create dose-response curves to evaluate whether the observed cytokine modulation was dependent on catecholamine concentration.
RESULTS
Incubation of blood with epinephrine and norepinephrine significantly increased LPS-stimulated production of IL-10, compared with the control. Epinephrine and norepinephrine significantly decreased LPS-stimulated production of TNF-α, compared with the control. Epinephrine and norepinephrine did not significantly alter LPS-stimulated production of IL-6. Dobutamine did not alter catecholamine production.
CONCLUSIONS AND CLINICAL RELEVANCE
Epinephrine and norepinephrine, but not dobutamine, had immunomodulatory effects on LPS-stimulated TNF-α and IL-10 production in blood from healthy dogs in this in vitro model of sepsis. Data suggested that dobutamine may have immune system-sparing effects in dogs with sepsis.
Topics: Animals; Dobutamine; Dogs; Epinephrine; Interleukin-10; Interleukin-6; Lipopolysaccharides; Norepinephrine; Tumor Necrosis Factor-alpha
PubMed: 33904806
DOI: 10.2460/ajvr.82.5.374 -
BMC Infectious Diseases Nov 2021The use of dobutamine in patients with sepsis is questionable currently. As the benefit of dobutamine in septic patients is unclear, we aimed to evaluate whether the use...
BACKGROUND
The use of dobutamine in patients with sepsis is questionable currently. As the benefit of dobutamine in septic patients is unclear, we aimed to evaluate whether the use of dobutamine was associated with decreased hospital mortality in sepsis patients.
METHODS
Based on the analysis of MIMIC III public database, we performed a big-data, real world study. According to the use of dobutamine or not, patients were categorized as the dobutamine group or non dobutamine group.We used propensity score matched (PSM) analysis to adjust for confoundings. The primary outcome was hospital mortality.
RESULTS
In the present study, after screening 38,605 patients, 2826 patients with sepsis were included. 121 patients were in dobutamine group and 2165 patients were in non dobutamine group. Compared with patients in non-dobutamine group, patients in dobutamine group had a lower MAP, higher HR, higher RR, higher severity of illness scores. 72 of 121 patients (59.5%) in the dobutamine group and 754 of 2165 patients (34.8%) in the non-dobutamine group died in the hospital, which resulted in a significant between-group difference (OR 1.56, 95% CI 1.01-2.40; P = 0.000). For the secondary outcomes, patients in dobutamine group received more MV use, more renal replacement therapy use, had longer ICU stay durations and more cardiac arrhythmias than those in non-dobutamine group. After adjusting for confoundings between groups by PSM analysis, hospital mortality was consistently higher in dobutamine group than that in non-dobutamine group (60.2% vs. 49.4%, OR 1.55, 95% CI 1.01-2.37; P = 0.044).
CONCLUSIONS
Among patients with sepsis, our study showed that the use of dobutamine was not associated with decreased hospital mortality. Further large scale, randomized controlled studies are warrented to confirm our findings.
Topics: Dobutamine; Hospital Mortality; Humans; Intensive Care Units; Propensity Score; Renal Replacement Therapy; Sepsis
PubMed: 34758739
DOI: 10.1186/s12879-021-06852-8 -
Brazilian Journal of Cardiovascular... Jul 2023Fuziline is one of the many antioxidants currently being tested to treat cardiac damage. In our study, histopathological and biochemical effects of fuziline were...
INTRODUCTION
Fuziline is one of the many antioxidants currently being tested to treat cardiac damage. In our study, histopathological and biochemical effects of fuziline were investigated in mice with dobutamine-induced heart damage in vitro.
METHODS
Thirty-two adult male BALB/c mice, average weight of 18-20 g, were randomly divided into four groups - Group 1 (sham, n=8), Group 2 (control, dobutamine, n=8), Group 3 (treatment 1, dobutamine + fuziline, n=8), and Group 4 (treatment 2, fuziline, n=8). Biochemical parameters and total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI) values were measured. Interleukin 1 beta (IL-1β), NLR family, pyrin domain containing protein 3 (NLRP3), 8-hydroxy-deoxyguanosine (8-OHDG), gasdermin D (GSDMD), and galectin 3 (GAL-3) levels were analyzed by enzyme-linked immunosorbent assay method, and histopathological examination of heart tissues was performed.
RESULTS
When dobutamine + fuziline and fuziline groups were compared, troponin-I (P<0.05), NLRP3 (P<0.001), GSDMD (P<0.001), 8-OHDG (P<0.001), IL-1β (P<0.001), and GAL-3 (P<0.05) were found to be statistically significant. TOS level was the highest in the dobutamine group (P<0.001) and TAS level was the highest in the fuziline group (P<0.001). OSI level was statistically significant between the groups (P<0.001). In histopathological examination, focal necrosis areas were smaller in the dobutamine + fuziline group than in the dobutamine group, and cardiac myocytes were better preserved.
CONCLUSION
Fuziline markedly reduced cardiac damage and pyroptosis in mice with dobutamine-induced heart damage by lowering the levels of GSDMD, 8-OHDG, IL-1β, and GAL-3. It also prevented necrosis of cardiac myocytes in histopathological evaluation.
Topics: Mice; Male; Animals; Dobutamine; NLR Family, Pyrin Domain-Containing 3 Protein; Oxidative Stress; Antioxidants; Necrosis; Heart Injuries
PubMed: 37402273
DOI: 10.21470/1678-9741-2022-0251 -
British Journal of Clinical Pharmacology Sep 2022To determine whether the known single nucleotide polymorphisms in adrenoreceptor associated genes affect the haemodynamic response to dobutamine in critically ill...
AIMS
To determine whether the known single nucleotide polymorphisms in adrenoreceptor associated genes affect the haemodynamic response to dobutamine in critically ill neonates.
METHODS
Alleles in the known genetic single nucleotide polymorphisms in β1- and β2-adrenoceptor (AR) genes and Gs protein α-subunit gene (GNAS) possibly affecting inotropic effect were identified in patients of neonatal dobutamine pharmacokinetic-pharmacodynamic study. Linear mixed-effect models were used to describe the effect of genetic polymorphisms to heart rate (HR), left ventricular output (LVO) and right ventricular output (RVO) during dobutamine treatment.
RESULTS
Twenty-six neonates (5 term, 21 preterm) were studied. Dobutamine plasma concentration and exposure time respective HR (adjusted to gestational age) is dependent on β1-AR Arg389Gly polymorphism so that in G/G (Gly) homozygotes and G/C heterozygotes dobutamine increases HR more than in C/C (Arg) homozygotes, with parameter estimate (95% CI) of 38.3 (15.8-60.7) beats/min per AUC of 100 μg L h, P = .0008. LVO (adjusted to antenatal glucocorticoid administration and illness severity) and RVO (adjusted to gestational age and illness severity) is dependent on GNAS c.393C > T polymorphism so that in T/T homozygotes and C/T heterozygotes but not in C/C homozygotes LVO and RVO increase with dobutamine treatment, 24.5 (6.2-42.9) mL kg min per AUC of 100 μg L h, P = .0095 and 33.2 (12.1-54.3) mL kg min per AUC of 100 μg L h, P = .0025, respectively.
CONCLUSION
In critically ill neonates, β1-AR Arg389Gly and GNAS c.393C > T polymorphisms may play a role in the haemodynamic response to dobutamine during the first hours and days of life.
Topics: Critical Illness; Dobutamine; Female; Heart Rate; Humans; Infant, Newborn; Pharmacogenetics; Polymorphism, Single Nucleotide; Pregnancy
PubMed: 35437830
DOI: 10.1111/bcp.15357 -
PloS One 2014Although dobutamine is widely used in neonatal clinical practice, the evidence for its use in this specific population is not clear. We conducted a systematic review of... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Although dobutamine is widely used in neonatal clinical practice, the evidence for its use in this specific population is not clear. We conducted a systematic review of the use of dobutamine in juvenile animals to determine whether the evidence from juvenile animal experiments with dobutamine supported the design of clinical trials in neonatal/paediatric population.
METHODS
Studies were identified by searching MEDLINE (1946-2012) and EMBASE (1974-2012). Articles retrieved were independently reviewed by three authors and only those concerning efficacy and safety of the drug in juvenile animals were included. Only original articles published in English and Spanish were included.
RESULTS
Following our literature search, 265 articles were retrieved and 24 studies were included in the review: 17 focused on neonatal models and 7 on young animal models. Although the aims and design of these studies, as well as the doses and ages analysed, were quite heterogeneous, the majority of authors agree that dobutamine infusion improves cardiac output in a dose dependent manner. Moreover, the cardiovascular effects of dobutamine are influenced by postnatal age, as well as by the dose used and the duration of the therapy. There is inadequate information about the effects of dobutamine on cerebral perfusion to draw conclusions.
CONCLUSION
There is enough preclinical evidence to ensure that dobutamine improves cardiac output, however to better understand its effects in peripheral organs, such as the brain, more specific and well designed studies are required to provide additional data to support the design of clinical trials in a paediatric population.
Topics: Adrenergic beta-1 Receptor Agonists; Age Factors; Animals; Animals, Newborn; Cardiotonic Agents; Cardiovascular System; Dobutamine; Drug Evaluation, Preclinical; Humans; Models, Animal
PubMed: 24755688
DOI: 10.1371/journal.pone.0095644 -
Beta blocker therapy, decompensated heart failure, and inotropic interactions: current perspectives.The Israel Medical Association Journal... Mar 2012Beta blockers are a fundamental treatment in chronic heart failure (HF), yet concern and disagreement regarding their role in the treatment of decompensated HF and... (Review)
Review
Beta blockers are a fundamental treatment in chronic heart failure (HF), yet concern and disagreement regarding their role in the treatment of decompensated HF and during hospitalization are common in clinical practice. This review summarizes the literature on various aspects of beta blocker treatment during acute and chronic decompensated HF. In recent years evidence has accumulated concerning the efficacy and tolerability of beta blockers in decompensated HF. Clinical analyses show that withdrawal of chronic beta blockade should be avoided when possible during hospitalization and that beta blockertherapy be initiated as soon as hemodynamic stability and a euvolemic state are achieved. This strategy may increase adherence to beta blockers after discharge and lower rehospitalization and mortality rates. We also discuss the various positive inotrope regimens (phosphodiesterase inhibitors, levosimendan, dobutamine) and their interactions with beta blockers in decompensated HF.
Topics: Acute Disease; Adrenergic beta-Antagonists; Cardiotonic Agents; Chronic Disease; Dobutamine; Drug Interactions; Drug Therapy, Combination; Heart Failure; Hospitalization; Humans; Hydrazones; Phosphodiesterase Inhibitors; Practice Guidelines as Topic; Pyridazines; Simendan
PubMed: 22675861
DOI: No ID Found -
Anaesthesia Oct 2009In view of the controversy over the use of inotropes in free tissue transfer surgery, we assessed the effect of different intra-operative dobutamine infusion rates on... (Randomized Controlled Trial)
Randomized Controlled Trial
In view of the controversy over the use of inotropes in free tissue transfer surgery, we assessed the effect of different intra-operative dobutamine infusion rates on blood flow in the anastomosed recipient artery. Twenty patients undergoing head and neck tumour resection and immediate reconstructive surgery with free tissue transfer were recruited. After completion of the microvascular anastomoses, patients received dobutamine infusions of 2, 4 and 6 microg x kg(-1) x min(-1) in a randomised order. After steady state dobutamine concentration was achieved, mean and maximum blood flow in the arterial anastomosis was measured at each concentration, using the Medi-Stim Butterfly Flowmeter system. Systemic haemodynamic parameters were simultaneously recorded using a pulse contour cardiac output system. Both mean and maximum blood flow increased significantly in the anastomosed artery at dobutamine infusions of 4 and 6 microg x kg(-1) x min(-1) and this was accompanied by increased cardiac output. This may improve free flap perfusion.
Topics: Adult; Aged; Cardiotonic Agents; Dobutamine; Dose-Response Relationship, Drug; Female; Head and Neck Neoplasms; Hemodynamics; Humans; Intraoperative Care; Male; Microcirculation; Microsurgery; Middle Aged; Plastic Surgery Procedures; Surgical Flaps
PubMed: 19735400
DOI: 10.1111/j.1365-2044.2009.06055.x -
Arquivos Brasileiros de Cardiologia Feb 2013Several studies have reported the benefits of beta-blockers (BB) for patients presenting with systolic heart failure. however, many patients hospitalized as a result of... (Review)
Review
Several studies have reported the benefits of beta-blockers (BB) for patients presenting with systolic heart failure. however, many patients hospitalized as a result of acute heart failure are already using BB and require dobutamine for arterial hypotension and low cardiac output. Therefore, a decision must be made regarding whether BB should be maintained or even started in such cases. The aim of this study was to establish whether there is evidence supporting the safety andyeffectiveness of BB together with dobutamine for patients presenting with acute decompensated heart failure (ADHF). We conducted a search of the English-language literature in the databases MEDLINE, ISI Web of Science, Virtual Health Library, Cochrane Library and the CAPES Portal of Scientific Journals to identify related studies. Additional literature was obtained through the review of relevant references in the identified articles. The expected outcomes included information on the prognosis (in-hospital and on follow-up mortality, number of days of hospitalization and readmission),yeffectiveness and safety (worsening of symptoms, shock, intolerance) of the concomitant use of these drugs in hospitalized patients with ADHF and low cardiac output. This review included nine studies. however, no randomized clinical trials on this subject were found. Most studies include a low number of patients, and no studies addressing the safety of the concomitant use of these drugs were found. The resulting data suggest that a careful literature review did not supply evidence for the systematic use of BB in patients with low cardiac output syndrome who require dobutamine for inotropic support.
Topics: Acute Disease; Adrenergic beta-Antagonists; Cardiotonic Agents; Dobutamine; Heart Failure; Humans
PubMed: 23503830
DOI: 10.5935/abc.20130034 -
Anesthesiology Aug 2023Conflicting evidence exists regarding the risks and benefits of inotropic therapies during cardiac surgery, and the extent of variation in clinical practice remains... (Observational Study)
Observational Study
BACKGROUND
Conflicting evidence exists regarding the risks and benefits of inotropic therapies during cardiac surgery, and the extent of variation in clinical practice remains understudied. Therefore, the authors sought to quantify patient-, anesthesiologist-, and hospital-related contributions to variation in inotrope use.
METHODS
In this observational study, nonemergent adult cardiac surgeries using cardiopulmonary bypass were reviewed across a multicenter cohort of academic and community hospitals from 2014 to 2019. Patients who were moribund, receiving mechanical circulatory support, or receiving preoperative or home inotropes were excluded. The primary outcome was an inotrope infusion (epinephrine, dobutamine, milrinone, dopamine) administered for greater than 60 consecutive min intraoperatively or ongoing upon transport from the operating room. Institution-, clinician-, and patient-level variance components were studied.
RESULTS
Among 51,085 cases across 611 attending anesthesiologists and 29 hospitals, 27,033 (52.9%) cases received at least one intraoperative inotrope, including 21,796 (42.7%) epinephrine, 6,360 (12.4%) milrinone, 2,000 (3.9%) dobutamine, and 602 (1.2%) dopamine (non-mutually exclusive). Variation in inotrope use was 22.6% attributable to the institution, 6.8% attributable to the primary attending anesthesiologist, and 70.6% attributable to the patient. The adjusted median odds ratio for the same patient receiving inotropes was 1.73 between 2 randomly selected clinicians and 3.55 between 2 randomly selected institutions. Factors most strongly associated with increased likelihood of inotrope use were institutional medical school affiliation (adjusted odds ratio, 6.2; 95% CI, 1.39 to 27.8), heart failure (adjusted odds ratio, 2.60; 95% CI, 2.46 to 2.76), pulmonary circulation disorder (adjusted odds ratio, 1.72; 95% CI, 1.58 to 1.87), loop diuretic home medication (adjusted odds ratio, 1.55; 95% CI, 1.42 to 1.69), Black race (adjusted odds ratio, 1.49; 95% CI, 1.32 to 1.68), and digoxin home medication (adjusted odds ratio, 1.48; 95% CI, 1.18 to 1.86).
CONCLUSIONS
Variation in inotrope use during cardiac surgery is attributable to the institution and to the clinician, in addition to the patient. Variation across institutions and clinicians suggests a need for future quantitative and qualitative research to understand variation in inotrope use affecting outcomes and develop evidence-based, patient-centered inotrope therapies.
Topics: Humans; Male; Female; Adolescent; Adult; Middle Aged; Aged; Aged, 80 and over; Myocardial Contraction; Cardiotonic Agents; Cardiac Surgical Procedures; Epinephrine; Dopamine; Dobutamine; Milrinone; Intraoperative Care
PubMed: 37094103
DOI: 10.1097/ALN.0000000000004593