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Circulation Research May 2024Loss or dysregulation of the normally precise control of heart rate via the autonomic nervous system plays a critical role during the development and progression of... (Review)
Review
Loss or dysregulation of the normally precise control of heart rate via the autonomic nervous system plays a critical role during the development and progression of cardiovascular disease-including ischemic heart disease, heart failure, and arrhythmias. While the clinical significance of regulating changes in heart rate, known as the chronotropic effect, is undeniable, the mechanisms controlling these changes remain not fully understood. Heart rate acceleration and deceleration are mediated by increasing or decreasing the spontaneous firing rate of pacemaker cells in the sinoatrial node. During the transition from rest to activity, sympathetic neurons stimulate these cells by activating β-adrenergic receptors and increasing intracellular cyclic adenosine monophosphate. The same signal transduction pathway is targeted by positive chronotropic drugs such as norepinephrine and dobutamine, which are used in the treatment of cardiogenic shock and severe heart failure. The cyclic adenosine monophosphate-sensitive hyperpolarization-activated current (I) in pacemaker cells is passed by hyperpolarization-activated cyclic nucleotide-gated cation channels and is critical for generating the autonomous heartbeat. In addition, this current has been suggested to play a central role in the chronotropic effect. Recent studies demonstrate that cyclic adenosine monophosphate-dependent regulation of HCN4 (hyperpolarization-activated cyclic nucleotide-gated cation channel isoform 4) acts to stabilize the heart rate, particularly during rapid rate transitions induced by the autonomic nervous system. The mechanism is based on creating a balance between firing and recently discovered nonfiring pacemaker cells in the sinoatrial node. In this way, hyperpolarization-activated cyclic nucleotide-gated cation channels may protect the heart from sinoatrial node dysfunction, secondary arrhythmia of the atria, and potentially fatal tachyarrhythmia of the ventricles. Here, we review the latest findings on sinoatrial node automaticity and discuss the physiological and pathophysiological role of HCN pacemaker channels in the chronotropic response and beyond.
Topics: Humans; Animals; Heart Rate; Sinoatrial Node; Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; Biological Clocks
PubMed: 38723033
DOI: 10.1161/CIRCRESAHA.123.323250 -
Scandinavian Cardiovascular Journal :... Dec 2023Dobutamine effects on the relationships of the peak velocity of left ventricular (LV) long-axis systolic motion (s') with systolic excursion (SExc), systolic duration...
BACKGROUND
Dobutamine effects on the relationships of the peak velocity of left ventricular (LV) long-axis systolic motion (s') with systolic excursion (SExc), systolic duration (SDur) and heart rate, of LV long-axis early diastolic excursion (EDExc) with SExc, and of the peak velocity of LV long-axis early diastolic motion (e') with EDExc, early diastolic duration (EDDur) and isovolumic relaxation time (IVRT') are unknown.
METHODS
Two groups of adult subjects, one young and healthy ( = 10), and one with impaired LV long-axis function ( = 10), were studied, with the aim of identifying consistent findings for the two groups and for the septal and lateral walls. Dobutamine was infused at doses of 5 and 10 µg/kg/min. The relationships between tissue Doppler imaging (TDI) variables acquired before and during dobutamine infusion were analysed using mixed effect multivariate regression modelling.
RESULTS
In both groups, heart rate increased and SDur decreased during dobutamine infusion, and there were independent inverse correlations of SDur with heart rate and dobutamine dose. In contrast, there was no change in EDDur during dobutamine infusion, and no consistent changes in IVRT' independent of heart rate. s' was positively correlated with SExc and inversely correlated with SDur, and there were positive correlations between EDExc and SExc and between e' and EDExc.
CONCLUSION
Dobutamine increases s' due to effects on both systolic excursion and duration and it increases e' due to the associated increases in systolic and early diastolic excursion. A lack of effect on diastolic times does not support the presence of a lusitropic effect of dobutamine.
Topics: Adult; Humans; Dobutamine; Ventricular Function, Left; Systole; Diastole; Heart Ventricles; Ventricular Dysfunction, Left
PubMed: 37128633
DOI: 10.1080/14017431.2023.2205070 -
Research in Veterinary Science Feb 2024This retrospective study aimed to assess the incidence of hypotension and the subsequent administration of dobutamine in horses anesthetized with isoflurane and...
This retrospective study aimed to assess the incidence of hypotension and the subsequent administration of dobutamine in horses anesthetized with isoflurane and romifidine during elective surgery. Time from induction of anaesthesia to administration of dobutamine was registered, as well as the time and dose needed to restore mean arterial pressure (MAP) ≥ 70 mmHg. Additionally, the influence of patient and anaesthesia related parameters on the need for dobutamine supplementation was evaluated. In total, 118 horses were included in this retrospective study. Dobutamine was administered to effect when MAP<70 mmHg. Data registered: patient weight, acepromazine premedication, body position, administration of intraoperative ketamine bolus, locoregional anaesthesia, mechanical ventilation, duration of anaesthesia, dose and duration of dobutamine administration, heart rate, MAP before dobutamine administration, MAP and time required to increase MAP≥70 mmHg. Dobutamine infusion was needed in 54.2% of the horses 30 ± 17 min after isoflurane-romifidine anaesthesia started. Dobutamine 0.55 ± 0.18 μg kg min achieved a MAP≥70 mmHg in 12 ± 8 min. Duration of dobutamine infusion was 56 ± 37 min. An univariable logistic regression showed a significant association between dobutamine and acepromazine administration (p = 0.01; OR = 3.43), anaesthesia time (p = 0.02; OR = 2.41) and dorsal recumbency (p < 0.001; OR = 8.40). In a multivariable logistic regression, only dorsal recumbency significantly increased the need for dobutamine supplementation (p < 0.001; OR = 7.70). There was no significant association between patient weight (p = 0.11; OR = 1), locoregional anaesthesia (p = 0.07; OR = 0.47), administration of a ketamine bolus (p = 0.95; OR = 0.98) or volume controlled ventilation (p = 0.94; OR = 1.04) and dobutamine administration. Low doses of dobutamine were suitable to restore MAP above 70 mmHg within a limited time period. Only dorsal recumbency increased the need of dobutamine administration.
Topics: Horses; Animals; Isoflurane; Dobutamine; Ketamine; Anesthetics, Inhalation; Acepromazine; Retrospective Studies; Blood Pressure; Anesthesia; Imidazoles
PubMed: 38154415
DOI: 10.1016/j.rvsc.2023.105119 -
BMC Medicine Jul 2023It is unclear whether dobutamine, commonly used clinically in echocardiography and short-term congestive heart failure treatment for promoting increased myocardial...
BACKGROUND
It is unclear whether dobutamine, commonly used clinically in echocardiography and short-term congestive heart failure treatment for promoting increased myocardial contractility, affects brain microcirculatory behavior. Cerebral microcirculation plays an important role in ensuring adequate oxygen transport. Therefore, we investigated the effects of dobutamine on cerebral hemodynamics.
METHODS
Forty-eight healthy volunteers without cardiovascular or cerebrovascular disease underwent MRI to obtain cerebral blood flow (CBF) maps using 3D pseudocontinuous arterial spin labeling before and during the dobutamine stress test. Additionally, cerebrovascular morphology was obtained based on 3D-time-off-light (3D-TOF) magnetic resonance angiography (MRA). Electrocardiogram, heart rate (HR), respiration rate (RR), blood pressure, and blood oxygen were simultaneously recorded before and during dobutamine injection and during recovery (not during MRI). The anatomic features of the circle of Willis and the basilar artery (BA) diameter were assessed on MRA images by two radiologists with extensive neuroimaging experience. Binary logistic regression was used to test for the independent determinants of CBF changes.
RESULTS
HR, RR, systolic (SBP), and diastolic blood pressure (DBP) significantly increased after dobutamine infusion. Blood oxygen levels remained similar. Compared to the CBF in the resting state, the CBF values exhibited significantly lower CBF levels in both grey matter and white matter. Furthermore, compared with the CBF in the resting state, that in the stress state was decreased in the anterior circulation, mainly in the frontal lobe (voxel level P < 0.001, pixel level P < 0.05). Logistic regression showed that body mass index (BMI; odds ratio [OR] 5.80, 95% confidence interval [CI] 1.60-21.01, P = 0.008], resting SBP (OR 0.64, 95% CI 0.45-0.92, P = 0.014), and BA diameter (OR 11.04, 95% CI 1.05-116.53, P = 0.046) were significantly associated with frontal lobe CBF changes.
CONCLUSIONS
Dobutamine-induced stress significantly decreased CBF in the frontal lobe anterior circulation. Individuals with a high BMI and low SBP during the dobutamine stress test are more likely to have a stress-induced CBF decrease. Thus, attention should be paid to blood pressure, BMI, and cerebrovascular morphology of patients undergoing dobutamine stress echocardiography or those receiving intensive care or anesthesia.
Topics: Humans; Adult; Dobutamine; Spin Labels; Microcirculation; Magnetic Resonance Imaging; Cerebrovascular Circulation; Oxygen
PubMed: 37400817
DOI: 10.1186/s12916-023-02928-1 -
Journal of Clinical Medicine Jun 2024Rest and stress echocardiography (SE) play a fundamental role in the evaluation of aortic valve stenosis (AS). According to the current guidelines for the... (Review)
Review
Rest and stress echocardiography (SE) play a fundamental role in the evaluation of aortic valve stenosis (AS). According to the current guidelines for the echocardiographic evaluation of patients with aortic stenosis, four broad categories can be defined: high-gradient AS (mean gradient ≥ 40 mmHg, peak velocity ≥ 4 m/s, aortic valve area (AVA) ≤ 1 cm or indexed AVA ≤ 0.6 cm/m); low-flow, low-gradient AS with reduced ejection fraction (mean gradient < 40 mmHg, AVA ≤ 1 cm, left ventricle ejection fraction (LVEF) < 50%, stroke volume index (Svi) ≤ 35 mL/m); low-flow, low-gradient AS with preserved ejection fraction (mean gradient < 40 mmHg, AVA ≤ 1 cm, LVEF ≥ 50%, SVi ≤ 35 mL/m); and normal-flow, low-gradient AS with preserved ejection fraction (mean gradient < 40 mmHg, AVA ≤ 1 cm, indexed AVA ≤ 0.6 cm/m, LVEF ≥ 50%, SVi > 35 mL/m). Aortic valve replacement (AVR) is indicated with the onset of symptoms development or LVEF reduction. However, there is often mismatch between resting transthoracic echocardiography findings and patient's symptoms. In these discordant cases, SE and CT calcium scoring are among the indicated methods to guide the management decision making. Additionally, due to the increasing evidence that in asymptomatic severe aortic stenosis an early AVR instead of conservative treatment is associated with better outcomes, SE can help identify those that would benefit from an early AVR by revealing markers of poor prognosis. Low-flow, low-gradient AS represents a challenge both in diagnosis and in therapeutic management. Low-dose dobutamine SE is the recommended method to distinguish true-severe from pseudo-severe stenosis and assess the existence of flow (contractile) reserve to appropriately guide the need for intervention in these patients.
PubMed: 38930024
DOI: 10.3390/jcm13123495 -
JACC. Advances Jul 2023Cardiogenic shock is associated with poor clinical outcomes. There is a paucity of prospective data examining the efficacy and safety of inotropic therapy in patients...
BACKGROUND
Cardiogenic shock is associated with poor clinical outcomes. There is a paucity of prospective data examining the efficacy and safety of inotropic therapy in patients with cardiogenic shock and renal dysfunction.
OBJECTIVES
This study sought to examine the treatment effect of milrinone compared to dobutamine in relation to renal function.
METHODS
In this post hoc analysis of the DOREMI (Milrinone as Compared with Dobutamine in the Treatment of Cardiogenic Shock) trial, we examined clinical outcomes with milrinone compared to dobutamine after stratification based on baseline estimated glomerular filtration rate (eGFR) 60 ml/min/1.73 m and acute kidney injury (AKI). The primary outcome was the composite of in-hospital death from any cause, resuscitated cardiac arrest, receipt of a cardiac transplant or mechanical circulatory support, nonfatal myocardial infarction, transient ischemic attack or stroke, or initiation of renal replacement therapy.
RESULTS
Baseline eGFR <60 ml/min/1.73 m and AKI were observed in 78 (45%) and 124 (65%) of patients, respectively. The primary outcome and death from any cause occurred in 99 (52%) and 76 (40%) patients, respectively. eGFR <60 ml/min/1.73 m did not appear to modulate the treatment effect of milrinone compared to dobutamine. In contrast, there was a significant interaction between the treatment effect of milrinone compared to dobutamine and AKI with respect to the primary outcome ( interaction = 0.02) and death ( interaction = 0.04). The interaction was characterized by lower risk of primary outcome and death with milrinone compared to dobutamine in patients without, but not with, AKI.
CONCLUSIONS
In patients requiring inotropic support for cardiogenic shock, baseline renal dysfunction and AKI are common. A modulating effect of AKI on the relative efficacy of milrinone compared to dobutamine was observed, characterized by attenuation of a potential clinical benefit with milrinone compared to dobutamine in patients who develop AKI.
PubMed: 38938997
DOI: 10.1016/j.jacadv.2023.100393 -
Neurological Sciences : Official... Jul 2024Post-sepsis psychiatric disorder, encompassing anxiety, depression, post-traumatic stress disorder and delirium, is a highly prevalent complication secondary to sepsis,... (Review)
Review
Post-sepsis psychiatric disorder, encompassing anxiety, depression, post-traumatic stress disorder and delirium, is a highly prevalent complication secondary to sepsis, resulting in a marked increase in long-term mortality among affected patients. Regrettably, psychiatric impairment associated with sepsis is frequently disregarded by clinicians. This review aims to summarize recent advancements in the understanding of the pathophysiology, prevention, and treatment of post-sepsis mental disorder, including coronavirus disease 2019-related psychiatric impairment. The pathophysiology of post-sepsis psychiatric disorder is complex and is known to involve blood-brain barrier disruption, overactivation of the hypothalamic-pituitary-adrenal axis, neuroinflammation, oxidative stress, neurotransmitter dysfunction, programmed cell death, and impaired neuroplasticity. No unified diagnostic criteria for this disorder are currently available; however, screening scales are often applied in its assessment. Modifiable risk factors for psychiatric impairment post-sepsis include the number of experienced traumatic memories, the length of ICU stay, level of albumin, the use of vasopressors or inotropes, daily activity function after sepsis, and the cumulative dose of dobutamine. To contribute to the prevention of post-sepsis psychiatric disorder, it may be beneficial to implement targeted interventions for these modifiable risk factors. Specific therapies for this condition remain scarce. Nevertheless, non-pharmacological approaches, such as comprehensive nursing care, may provide a promising avenue for treating psychiatric disorder following sepsis. In addition, although several therapeutic drugs have shown preliminary efficacy in animal models, further confirmation of their potential is required through follow-up clinical studies.
Topics: Humans; Sepsis; COVID-19; Mental Disorders; Stress Disorders, Post-Traumatic; SARS-CoV-2; Delirium
PubMed: 38381393
DOI: 10.1007/s10072-024-07409-8 -
European Journal of Trauma and... Oct 2023One of the most common causes of a failure after replantation and revascularization surgeries is 'no reflow' from proximal artery that occurs, especially following crush...
PURPOSE
One of the most common causes of a failure after replantation and revascularization surgeries is 'no reflow' from proximal artery that occurs, especially following crush and avulsion injuries. In this study, we aimed to evaluate the effect of dobutamine treatment on salvage of replanted and revascularized digits.
METHODS
The patients with no reflow phenomenon detected in the salvage operations of replanted/revascularized digits between the years 2017 and 2020 were included in the study. Dobutamine treatment was infused at a rate of 4 µg·kg·min intraoperatively and of 2 µg·kg min postoperatively. Demographic data (age, sex), digit survival rate, ischemia time, and level of injury were retrospectively analysed. Pre-infusion, intraoperative and postoperative values of cardiac index (CI), mean arterial pressure (MAP), and heart rate (HR) were recorded.
RESULTS
The phenomenon of 'no reflow' was encountered in 35 digits of 22 patients who underwent salvage surgery due to vascular compromise. The survival rate in the revascularization group was 75%, while it was 42.1% in the replanted digits. Metaphysis level of proximal phalanx was the most common localization for 'no reflow' phenomenon. The least values of CI, MAP and HR to obtain sufficient perfusion in salvaged digits were as follows: 4.2 l.min.m, 76 mm Hg, and 83 beat·min, respectively.
CONCLUSIONS
It was demonstrated that dobutamine infusion at a rate of 4 µg·kg·min intraoperatively and at 2 µg·kg·min postoperatively has favorable effects on the vascular compromise derived from no reflow of proximal artery.
Topics: Humans; Fingers; Amputation, Traumatic; Dobutamine; Finger Injuries; Retrospective Studies; Replantation
PubMed: 37367969
DOI: 10.1007/s00068-023-02312-x -
Cureus Feb 2024The aim of this systematic review and meta-analysis was to compare the outcomes between milrinone and dobutamine in patients with cardiogenic shock. The search strategy... (Review)
Review
The aim of this systematic review and meta-analysis was to compare the outcomes between milrinone and dobutamine in patients with cardiogenic shock. The search strategy involved a comprehensive exploration of electronic databases, including PubMed, EMBASE, Cochrane Library, and Scopus from the the inception of each database up to the 31st of January 2024. A combination of keywords and Medical Subject Headings (MeSH) terms was employed to identify relevant studies. The outcomes assessed in this meta-analysis included all-cause in-hospital mortality, length of intensive care unit (ICU stay), and length of hospital stay. A total of seven studies were included in this meta-analysis enrolling 3,841 patients (2,331 in the dobutamine group and 1,510 in the milrinone group). Pooled analysis showed that the risk of all-cause mortality was significantly higher in patients receiving dobutamine compared to patients receiving milrinone (relative risk (RR): 1.43, 95% confidence interval (CI): 1.02 to 2.01, p-value: 0.04). However, the length of hospital stay and length of ICU stay were not significantly different between the two groups. Limited data are available to favor the use of one inotropic agent over another. Dobutamine might lead to a shorter hospital length of stay, but there is also a risk of increased all-cause mortality. Larger randomized studies with adequate power are needed to validate these observations.
PubMed: 38544600
DOI: 10.7759/cureus.54948 -
Medicina (Kaunas, Lithuania) Apr 2024The key objective in the hemodynamic treatment of septic shock is the optimization of tissue perfusion and oxygenation. This is usually achieved by the utilization of... (Review)
Review
The key objective in the hemodynamic treatment of septic shock is the optimization of tissue perfusion and oxygenation. This is usually achieved by the utilization of fluids, vasopressors, and inotropes. Dobutamine is the inotrope most commonly recommended and used for this purpose. Despite the fact that dobutamine was introduced almost half a century ago in the treatment of septic shock, and there is widespread use of the drug, several aspects of its pharmacodynamics remain poorly understood. In normal subjects, dobutamine increases contractility and lacks a direct effect on vascular tone. This results in augmented cardiac output and blood pressure, with reflex reduction in systemic vascular resistance. In septic shock, some experimental and clinical research suggest beneficial effects on systemic and regional perfusion. Nevertheless, other studies found heterogeneous and unpredictable effects with frequent side effects. In this narrative review, we discuss the pharmacodynamic characteristics of dobutamine and its physiologic actions in different settings, with special reference to septic shock. We discuss studies showing that dobutamine frequently induces tachycardia and vasodilation, without positive actions on contractility. Since untoward effects are often found and therapeutic benefits are occasional, its profile of efficacy and safety seems low. Therefore, we recommend that the use of dobutamine in septic shock should be cautious. Before a final decision about its prescription, efficacy, and tolerance should be evaluated throughout a short period with narrow monitoring of its wanted and side effects.
Topics: Humans; Cardiac Output; Cardiotonic Agents; Dobutamine; Hemodynamics; Shock, Septic; Animals
PubMed: 38792934
DOI: 10.3390/medicina60050751