Correlations between heart sound components and hemodynamic variables.

Although the esophageal stethoscope is used for continuous auscultation during general anesthesia, few studies have investigated phonocardiographic data as a continuous hemodynamic index. In this study, we aimed to induce hemodynamic variations and clarify the relationship between the heart sounds and hemodynamic variables through an experimental animal study. Changes in the cardiac contractility and vascular resistance were induced in anesthetized pigs by administering dobutamine, esmolol, phenylephrine, and nicardipine. In addition, a decrease in cardiac output was induced by restricting the venous return by clamping the inferior vena cava (IVC). The relationship between the hemodynamic changes and changes in the heart sound indices was analyzed. Experimental data from eight pigs were analyzed. The mean values of the correlation coefficients of changes in S1 amplitude (ΔS1amp) with systolic blood pressure (ΔSBP), pulse pressure (ΔPP), and ΔdP/dt during dobutamine administration were 0.94, 0.96, and 0.96, respectively. The mean values of the correlation coefficients of ΔS1amp with ΔSBP, ΔPP, and ΔdP/dt during esmolol administration were 0.80, 0.82, and 0.86, respectively. The hemodynamic changes caused by the administration of phenylephrine and nicardipine did not correlate significantly with changes in the heart rate. The S1 amplitude of the heart sound was significantly correlated with the hemodynamic changes caused by the changes in cardiac contractility but not with the variations in the vascular resistance. Heart sounds can potentially provide a non-invasive monitoring method to differentiate the cause of hemodynamic variations.

Site-specific effects of dobutamine on cardiac conduction and refractoriness.

BACKGROUND: Isoproterenol, a non-specific beta agonist, is commonly used during electrophysiology studies (EPS). However, with the significant increase in the price of isoproterenol in 2015 and the increasing number of catheter ablations performed, the cost implications cannot be ignored. Dobutamine is a less expensive synthetic compound developed from isoproterenol with a similar mechanism to enhance cardiac conduction and shorten refractoriness, thus making it a feasible substitute with a lower cost. However, the use of dobutamine for EPS has not been well-reported in the literature. OBJECTIVE: To determine the site-specific effects of various doses of dobutamine on cardiac conduction and refractoriness and assess its safety during EPS. METHODS: From February 2020 to October 2020, 40 non-consecutive patients scheduled for elective EPS, supraventricular tachycardia, atrial fibrillation, and premature ventricular contraction ablations at a single center were consented and prospectively enrolled to assess the effect of dobutamine on the cardiac conduction system. At the end of each ablation procedure, measures of cardiac conduction and refractoriness were recorded at baseline and with incremental doses of dobutamine at 5, 10, 15, and 20 mcg/kg/min. For the primary analysis, the change per dose of dobutamine from baseline to each dosing level of dobutamine received by the patients, comparing atrioventricular node block cycle length (AVNBCL), ventricular atrial block cycle length (VABCL) and sinus cycle length (SCL), was tested using mixed-effect regression. For the secondary analysis, dobutamine dose level was tested for association with relative changes from baseline of each electrophysiologic parameter (SCL, AVNBCL, VABCL, atrioventricular node effective refractory period (AVNERP), AH, QRS, QT, QTc, atrial effective refractory period (AERP), ventricular effective refractory period (VERP), using mixed-effect regression. Changes in systolic and diastolic blood pressures were also assessed. The Holm-Bonferroni method was used to adjust for multiple testing. RESULTS: For the primary analysis there was no statistically significant change of AVNBCL and VABCL relative to SCL from baseline to each dose level of dobutamine. The SCL, AVNBCL, VABCL, AVNERP, AERP, VERP and the AH, and QT intervals all demonstrated a statistically significant decrease from baseline to at least one dose level with incremental dobutamine dosing. Two patients (5%) developed hypotension during the study and one patient (2.5%) received a vasopressor. Two patients (5%) had induced arrhythmias but otherwise no major adverse events were noted. CONCLUSION: In this study, there was no statistically significant change of AVNBCL and VABCL relative to SCL from baseline to any dose level of dobutamine. As expected, the AH and QT intervals, and the VABCL, VERP, AERP and AVNERP all significantly decreased from baseline to at least one dose level with an escalation in dobutamine dose. Dobutamine was well-tolerated and safe to use during EPS.

Dobutamine use in horses during romifidine and isoflurane anaesthesia.

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-1 min-1 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.

Effects of Catecholamines on Blood Flow in Preterm Infants: A Subanalysis of PICC-MBF Trial.

INTRODUCTION: This study evaluated the correlation between skin blood flow and systemic blood flow and whether skin blood flow can determine the circulatory effects of dopamine and dobutamine on blood flow in very low birth weight (VLBW) infants. METHODS: This study was a subanalysis of the PICC-MBF randomized controlled trial. The correlation between skin blood flow and echocardiographic findings was examined. Changes in skin blood flow and blood pressure before and after initiation or dose increase of dopamine and dobutamine were also evaluated. RESULTS: Two hundred and thirty-four participants underwent echocardiography. Skin blood flow was significantly correlated with supra vena cava (SVC) flow (r = 0.31, p < 0.001). Receiver operator characteristic analysis revealed that skin blood flow <17 mL/min effectively detected SVC flow <41 mL/min (area under the curve = 0.83, p < 0.001). Dobutamine significantly increased skin blood flow after initiation or dose increase (p = 0.033) without increasing blood pressure. However, dopamine significantly increased both skin blood flow (p = 0.010) and blood pressure (p < 0.001). CONCLUSIONS: Our findings indicated that skin blood flow could be used as a surrogate marker of systemic blood flow in VLBW infants and revealed differences in the effects of dopamine and dobutamine on circulation.

A Meta-Analysis of the Effects of Levosimendan on Cardiac Function and Outcomes in Patients with Sepsis.

Objective: To systematically evaluate the effect of levosimendan on cardiac function and outcomes in patients with sepsis. Method: We searched multiple databases including CNKI, VIP, WanFang Data, WOS, PubMed, EMbase, and The Cochrane Library up to February 2023. We targeted RCTs comparing levosimendan with dobutamine as a control for treating sepsis. After a rigorous screening and quality evaluation, 18 studies were selected for meta-analysis using Review Manager 5.4. Results: Out of 18 studies involving 980 sepsis patients, the meta-analysis revealed the following for the levosimendan group compared to dobutamine: (1) A significant reduction in mortality rate (OR = 0.63, 95% CI (0.42,0.95), P = .03). (2) Shortened ICU stay (MD = -2.55, 95% CI (-3.12, -1.98), P < .00001). (3) Increased left ventricular ejection fraction (LVEF) (MD = 6.05, 95%CI (5.28, 6.81), P < .00001) and cardiac index (CI) (MD = 0.47, 95%CI (0.35, 0.59), P < .00001). (4) Decreased blood lactate (Lac) (MD = -1.31, 95%CI (-1.73, -0.90), P < .00001) and troponin I (TnI) levels (MD = -0.43, 95%CI (-0.66, -0.21), P = .0002). (5) Reduced incidence of adverse events (OR = 0.43, 95% CI (0.23,0.81), P = .008). Conclusions: Compared to dobutamine, levosimendan substantially enhances cardiac function in sepsis patients, leading to improved outcomes and fewer adverse events.

Protective Effects of Fuziline on Dobutamine-Induced Heart Damage in Mice.

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-1ß), 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-1ß (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-1ß, and GAL-3. It also prevented necrosis of cardiac myocytes in histopathological evaluation.

Multiaxial pressure-strain analysis of regional myocardial work in the setting of graded coronary stenoses and dobutamine stress.

We present a detailed analysis of regional myocardial blood flow and work to better understand the effects of coronary stenoses and low-dose dobutamine stress. Our analysis is based on a unique open-chest model in anesthetized canines that features invasive hemodynamic monitoring, microsphere-based blood flow analysis, and an extensive three-dimensional (3-D) sonomicrometer array that provides multiaxial deformational assessments in the ischemic, border, and remote vascular territories. We use this model to construct regional pressure-strain loops for each territory and quantify the loop subcomponent areas that reflect myocardial work contributing to the ejection of blood and wasted work that does not. We demonstrate that reductions in coronary blood flow markedly alter the shapes and temporal relationships of pressure-strain loops, as well as the magnitudes of their total and subcomponent areas. Specifically, we show that moderate stenoses in the mid-left anterior descending coronary artery decrease regional midventricle myocardial work indices and substantially increase indices of wasted work. In the midventricle, these effects are most pronounced along the radial and longitudinal axes, with more modest effects along the circumferential axis. We further demonstrate that low-dose dobutamine can help to restore or even improve function, but often at the cost of increased wasted work. This detailed, multiaxial analysis provides unique insight into the physiology and mechanics of the heart in the presence of ischemia and low-dose dobutamine, with potential implications in many areas, including the detection and characterization of ischemic heart disease and the use of inotropic support for low cardiac output.NEW & NOTEWORTHY Our unique experimental model assesses cardiac pressure-strain relationships along multiple axes in multiple regions. We demonstrate that moderate coronary stenoses decrease regional myocardial work and increase wasted work and that low-dose dobutamine can help to restore myocardial function, but often with further increases in wasted work. Our findings highlight the significant directional variation of cardiac mechanics and demonstrate potential advantages of pressure-strain analyses over traditional, purely deformational measures, especially in characterizing physiological changes related to dobutamine.

Blood pressure control with phenylephrine or dobutamine: a randomized controlled trial comparing effects on cerebral and paravertebral tissue oxygen saturation measured with near-infrared spectroscopy.

Preserving haemodynamics is expected to positively affect tissue oxygen saturation. We hypothesized that maintaining mean arterial blood pressure (MAP) (using phenylephrine (PE) or dobutamine (Dobu)) would equally affect regional cerebral and paravertebral tissue saturation (rScO2 and rSpvO2, respectively). Thirty-four patients were randomly assigned to receive either PE or Dobu, in order to keep MAP within 20% of the preoperative value. Their effect on haemodynamics, rScO2 and rSpvO2 at thoracic level T3-T4, T9-T10 and lumbar level L1-L2 was calculated at different doses. Drug-induced haemodynamic effects differed between groups (∆MAP: -2%±21 and - 19%±17, ∆CI: -14.6%±14.6 and 24.1%±49.9, ∆HR: -21%±21 and 0%±16 for PE and Dobu, respectively). Both groups exhibited a significant decrease in rScO2, with a more pronounced decline in the PE group (-14.1%±16.1) compared to the Dobu group (-5.9%±10.6). There were no significant changes at the paravertebral level in either group, but a slight but statistically significant difference was detected between the two groups at T3-T4 and L1-L2. Current guidelines advocate maintaining adequate systemic blood pressures to prevent spinal cord ischaemia in specific procedures. However, it is still unknown which circulatory supportive drug is more beneficial for maintaining spinal cord perfusion. Our data indicates that, when used for maintenance of blood pressure within a 20% range of preoperative values, neither phenylephrine nor dobutamine affect paravertebral tissue saturation.

Effect of stress on the chronotropic and inotropic responses to ß-adrenergic agonists in isolated atria of KOß2 mice.

Altered sensitivity to the chronotropic and inotropic effects of catecholamines and reduction in ß1/ß2-adrenoceptor (ß1/ß2-AR) ratio were reported in failing and in senescent human heart, as well as in isolated atria and ventricle of rats submitted to stress. This was due to downregulation of ß1-AR with or without up-regulation of ß2-AR. AIMS: To investigate the stress-induced behavior of ß1-AR in the heart of mice expressing a non-functional ß2-AR subtype. The guiding hypothesis is that the absence of ß2-AR signaling will not affect the behavior of ß1-AR during stress and that those are independent processes. MATERIALS AND METHODS: The chronotropic and inotropic responses to ß-AR agonists in isolated atria of stressed mice expressing a non-functional ß2-AR were analyzed. The mRNA and protein expressions of ß1- and ß2-AR were also determined. KEY FINDINGS: No deaths were observed in mice under stress protocol. Atria of stressed mice displayed reduced sensitivity to isoprenaline compared to the controls, an effect that was abolished by the ß2- and ß1-AR antagonists 50 nM ICI118,551 and 300 nM CGP20712A, respectively. Sensitivity and maximum response to the ß-agonists dobutamine and salbutamol were not altered by stress or ICI118,551. The responses to dobutamine and salbutamol were prevented by CGP20712A. The expression of ß1-AR was reduced at protein levels. SIGNIFICANCE: Collectively, our data provide evidence that the cardiac ß2-AR is not essential for survival in a stressful situation and that the stress-induced reduction of ß1-AR expression was independent of the ß2-AR presence.

Assessment of Cardiac Energy Metabolism, Function, and Physiology in Patients With Heart Failure Taking Empagliflozin: The Randomized, Controlled EMPA-VISION Trial.

BACKGROUND: Sodium-glucose co-transporter 2 inhibitors (SGLT2i) have emerged as a paramount treatment for patients with heart failure (HF), irrespective of underlying reduced or preserved ejection fraction. However, a definite cardiac mechanism of action remains elusive. Derangements in myocardial energy metabolism are detectable in all HF phenotypes, and it was proposed that SGLT2i may improve energy production. The authors aimed to investigate whether treatment with empagliflozin leads to changes in myocardial energetics, serum metabolomics, and cardiorespiratory fitness. METHODS: EMPA-VISION (Assessment of Cardiac Energy Metabolism, Function and Physiology in Patients With Heart Failure Taking Empagliflozin) is a prospective, randomized, double-blind, placebo-controlled, mechanistic trial that enrolled 72 symptomatic patients with chronic HF with reduced ejection fraction (HFrEF; n=36; left ventricular ejection fraction ≤40%; New York Heart Association class ≥II; NT-proBNP [N-terminal pro-B-type natriuretic peptide] ≥125 pg/mL) and HF with preserved ejection fraction (HFpEF; n=36; left ventricular ejection fraction ≥50%; New York Heart Association class ≥II; NT-proBNP ≥125 pg/mL). Patients were stratified into respective cohorts (HFrEF versus HFpEF) and randomly assigned to empagliflozin (10 mg; n=35: 17 HFrEF and 18 HFpEF) or placebo (n=37: 19 HFrEF and 18 HFpEF) once daily for 12 weeks. The primary end point was a change in the cardiac phosphocreatine:ATP ratio (PCr/ATP) from baseline to week 12, determined by phosphorus magnetic resonance spectroscopy at rest and during peak dobutamine stress (65% of age-maximum heart rate). Mass spectrometry on a targeted set of 19 metabolites was performed at baseline and after treatment. Other exploratory end points were investigated. RESULTS: Empagliflozin treatment did not change cardiac energetics (ie, PCr/ATP) at rest in HFrEF (adjusted mean treatment difference [empagliflozin - placebo], -0.25 [95% CI, -0.58 to 0.09]; P=0.14) or HFpEF (adjusted mean treatment difference, -0.16 [95% CI, -0.60 to 0.29]; P=0.47]. Likewise, there were no changes in PCr/ATP during dobutamine stress in HFrEF (adjusted mean treatment difference, -0.13 [95% CI, -0.35 to 0.09]; P=0.23) or HFpEF (adjusted mean treatment difference, -0.22 [95% CI, -0.66 to 0.23]; P=0.32). No changes in serum metabolomics or levels of circulating ketone bodies were observed. CONCLUSIONS: In patients with either HFrEF or HFpEF, treatment with 10 mg of empagliflozin once daily for 12 weeks did not improve cardiac energetics or change circulating serum metabolites associated with energy metabolism when compared with placebo. Based on our results, it is unlikely that enhancing cardiac energy metabolism mediates the beneficial effects of SGLT2i in HF. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03332212.

Cardiac output affects the response to pulsed inhaled nitric oxide in mechanically ventilated anesthetized ponies determined by CT angiography of the lung.

OBJECTIVE: To measure changes in regional lung perfusion using CT angiography in mechanically ventilated, anesthetized ponies administered pulsed inhaled nitric oxide (PiNO) during hypotension and normotension. ANIMALS: 6 ponies for anesthetic 1 and 5 ponies for anesthetic 2. PROCEDURES: Ponies were anesthetized on 2 separate occasions, mechanically ventilated, and placed in dorsal recumbency within the CT gantry. Pulmonary arterial, right atrial, and facial arterial catheters were placed. During both anesthetics, PiNO was delivered for 60 minutes and then discontinued. Anesthetic 1: hypotension (mean arterial pressure < 70 mmHg) was treated using dobutamine after 30 minutes of PiNO delivery. Following the discontinuation of PiNO, dobutamine administration was discontinued in 3 ponies and was continued in 3 ponies. The lung was imaged at 30, 60, and 105 minutes. Anesthetic 2: hypotension persisted throughout anesthesia. The lung was imaged at 30, 60, and 90 minutes. At all time points, arterial and mixed venous blood samples were analyzed and cardiac output (Q˙t) was measured. Pulmonary perfusion was calculated from CT image analysis. RESULTS: During PiNO delivery, perfusion to well-ventilated lungs increased if ponies were normotensive, leading to increased arterial oxygenation, reduced alveolar dead space, and reduced alveolar to arterial oxygen tension gradient. When PiNO was stopped and dobutamine administration continued, alveolar dead space and venous admixture increased, in contrast to when dobutamine and PiNO were both discontinued. CLINICAL RELEVANCE: If PiNO is administered to mechanically ventilated, anesthetized ponies with concurrent hypotension and low Q˙t, this must be supported to achieve favorable redistribution of pulmonary perfusion to improve pulmonary gas exchange.

Oxygen-sensing pathways below autoregulatory threshold act to sustain myocardial oxygen delivery during reductions in perfusion pressure.

The coronary circulation has an innate ability to maintain constant blood flow over a wide range of perfusion pressures. However, the mechanisms responsible for coronary autoregulation remain a fundamental and highly contested question. This study interrogated the local metabolic hypothesis of autoregulation by testing the hypothesis that hypoxemia-induced exaggeration of the metabolic error signal improves the autoregulatory response. Experiments were performed on open-chest anesthetized swine during stepwise changes in coronary perfusion pressure (CPP) from 140 to 40 mmHg under normoxic (n = 15) and hypoxemic (n = 8) conditions, in the absence and presence of dobutamine-induced increases in myocardial oxygen consumption (MVO2) (n = 5-7). Hypoxemia (PaO2 < 40 mmHg) decreased coronary venous PO2 (CvPO2) ~ 30% (P < 0.001) and increased coronary blood flow ~ 100% (P < 0.001), sufficient to maintain myocardial oxygen delivery (P = 0.14) over a wide range of CPPs. Autoregulatory responsiveness during hypoxemia-induced reductions in CvPO2 were associated with increases of autoregulatory gain (Gc; P = 0.033) but not slope (P = 0.585) over a CPP range of 120 to 60 mmHg. Preservation of autoregulatory Gc (P = 0.069) and slope (P = 0.264) was observed during dobutamine administration ± hypoxemia. Reductions in coronary resistance in response to decreases in CPP predominantly occurred below CvPO2 values of ~ 25 mmHg, irrespective of underlying vasomotor reserve. These findings support the presence of an autoregulatory threshold under which oxygen-sensing pathway(s) act to preserve sufficient myocardial oxygen delivery as CPP is reduced during increases in MVO2 and/or reductions in arterial oxygen content.

[Comparative assessment of the effects of dobutamine and levosimendan on right ventricular ejection fraction in patients with biventricular heart failure].

Aim    The primary objective of this study was to comparatively assess the effects of levosimendan and dobutamine on RVEF, right ventricular diastolic function, and hormonal balance in patients with biventricular heart failure. The secondary objective was to investigate the relationship between the RVEF and the peak systolic velocity (Sa), an indicator of right ventricular systolic function, as measured by tissue Doppler echocardiography from the tricuspid annulus, and by the tricuspid annular plane systolic excursion (TAPSE).Material and Methods    The population of this cross-sectional, single-center, prospective study was comprised of 81 patients, who between December 2019 and January 2022, applied to the study health institution with diagnosis of ADHF. The study sample included 67 biventricular heart failure patients with left ventricular ejection fraction (LVEF) <35 % and RVEF <50 %, as measured by the ellipsoidal shell model, and who met the other study inclusion criteria. Of these 67 patients, 34 were treated with levosimendan, and 33 were treated with dobutamine. RVEF, LVEF, Sa, peak early (Ea) and peak late (Aa) annular velocities, Ea / Aa ratio, TAPSE, systolic pulmonary artery pressure (SPAP), n-terminal pro-brain natriuretic peptide (NT-pro BNP), and functional capacity (FC) were measured before treatment and at 48 hrs of treatment. The within group pre- and post-treatment differences (Δs) of these variables were compared.Results    RVEF, SPAP, and BNP, and FC significantly improved in both treatment groups (p<0.05 for all). Sa (p<0.01), TAPSE (p<0.01), LVEF (p<0.01), and Ea / Aa (p<0.05) improved only in the levosimendan group. The pre- and post-treatment Δs for RVEF, LVEF, SPAP, Sa, TAPSE, FC, and Ea / Aa were higher in the levosimendan group than in the dobutamine group (p<0.05 for all).Conclusion    Compared to dobutamine, levosimendan produced greater improvement in right ventricular systolic and diastolic function in patients with biventricular heart failure and in need of inotropic therapy support.

Comparative assessment of coronary physiology using transthoracic pulsed-wave Doppler and myocardial contrast echocardiography in rats.

BACKGROUND: Coronary physiology assessment in rodents by ultrasound is an excellent noninvasive and easy to perform technique, including pulsed-wave Doppler (PWD) and myocardial contrast echocardiography (MCE). Both techniques and the corresponding calculated parameters were investigated in this study at rest as well as their response to pharmacologically induced stress. METHODS: Left ventricular myocardial function was assessed in eight anaesthetised rats using transthoracic echocardiography. Coronary physiology was assessed by both PWD of the left coronary artery and MCE using a bolus method. Measurements were performed at rest and under stimulation with adenosine and dobutamine. Effects of stimulation on the calculated parameters were evaluated and rated by effect size (η2). RESULTS: Changes could be demonstrated by selected parameters of PWD and MCE. The clearest effect in PWD was found for diastolic peak velocity (η2 = 0.58). It increased from 528 ± 110 mm/s (mean ± standard deviation) at rest to 839 ± 342 mm/s (p = 0.001) with adenosine and 1093 ± 302 mm/s with dobutamine (p = 0.001). The most distinct effect from MCE was found for the normalised wash-in rate (η2 = 0.58). It increased from 1.95 ± 0.35% at rest to 3.87 ± 0.85% with adenosine (p = 0.001) and 3.72 ± 1.03% with dobutamine (p = 0.001). CONCLUSION: Induced changes in coronary physiology by adenosine and dobutamine could successfully be monitored using MCE and PWD in anaesthetised rats. Due to the low invasiveness of the measurements, this protocol could be used for longitudinal animal studies.

Equine echocardiography: Can dobutamine infusion correct alterations due to sedation with alpha-2 agonists?

For the echocardiographic examination horses should not be sedated unless absolutely necessary because this alters cardiac dimensions and indices of function. However, some horses do not tolerate the echocardiographic procedure and require sedation to conduct the examination safely and obtain good quality images. The objective of this study was to evaluate whether the concurrent infusion of dobutamine in horses sedated with romifidine counteracts the cardiovascular changes observed with sedation alone. Twelve healthy untrained Standardbred mares were used. Three echocardiographic examinations were performed on the same day for each subject: a) without any treatment under resting conditions (WT); b) under sedation with romifidine administered intravenously (RT); c) under sedation with romifidine and concurrent intravenous infusion with dobutamine (RDT). A three-hour washout period was observed between each examination and the order of the examinations was randomly decided by rolling a dice. The measurements on the images recorded were performed offline at the end of the study protocol and at this point the operator was blinded to the horse and treatment administered. Left ventricular internal diameter (LVID) in diastole, left ventricular free wall (LVFW) in systole, and fractional shortening (FS) were higher in the WT group compared with the other two groups. No differences in the other M-mode and B-mode values were observed. A continuous rate infusion of dobutamine did not counteract the alterations caused by sedation and led to similar echocardiographic measurements to those obtained after romifidine administration.

Cardiovascular effects of dobutamine, norepinephrine and phenylephrine in isoflurane-anaesthetized dogs administered dexmedetomidine-vatinoxan.

OBJECTIVE: To determine whether dobutamine, norepinephrine or phenylephrine infusions alleviate hypotension in isoflurane-anaesthetized dogs administered dexmedetomidine with vatinoxan. STUDY DESIGN: Balanced, randomized crossover trial. ANIMALS: A total of eight healthy Beagle dogs. METHODS: Each dog was anaesthetized with isoflurane (end-tidal isoflurane 1.3%) and five treatments: dexmedetomidine hydrochloride (2.5 µg kg-1) bolus followed by 0.9% saline infusion (DEX-S); dexmedetomidine and vatinoxan hydrochloride (100 µg kg-1) bolus followed by an infusion of 0.9% saline (DEX-VAT-S), dobutamine (DEX-VAT-D), norepinephrine (DEX-VAT-N) or phenylephrine (DEX-VAT-P). The dexmedetomidine and vatinoxan boluses were administered at baseline (T0) and the treatment infusion was started after 15 minutes (T15) if mean arterial pressure (MAP) was < 90 mmHg. The treatment infusion rate was adjusted every 5 minutes as required. Systemic haemodynamics were recorded at T0 and 10 (T10) and 45 (T45) minutes. A repeated measures analysis of covariance model was used. RESULTS: Most dogs had a MAP < 70 mmHg at T0 before treatment. Treatments DEX-S and DEX-VAT all significantly increased MAP at T10, but systemic vascular resistance index (SVRI) was significantly higher and cardiac index (CI) lower after DEX-S than after DEX-VAT. CI did not significantly differ between DEX-S and DEX-VAT-S at T45, while SVRI remained higher with DEX-S. Normotension was achieved by all vasoactive infusions in every dog, whereas MAP was below baseline with DEX-VAT-S, and higher than baseline with DEX-S at T45. Median infusion rates were 3.75, 0.25 and 0.5 µg kg-1 minute-1 for dobutamine, norepinephrine and phenylephrine, respectively. Dobutamine and norepinephrine increased CI (mean ± standard deviation, 3.35 ± 0.70 and 3.97 ± 1.24 L minute-1 m-2, respectively) and decreased SVRI, whereas phenylephrine had the opposite effect (CI 2.13 ± 0.45 L minute-1 m-2). CONCLUSIONS AND CLINICAL RELEVANCE: Hypotension in isoflurane-anaesthetized dogs administered dexmedetomidine and vatinoxan can be treated with either dobutamine or norepinephrine.

Altered cardiac ß1 responsiveness in hyperthermic older adults.

Compared with younger adults, passive heating induced increases in cardiac output are attenuated by ∼50% in older adults. This attenuated response may be associated with older individuals' inability to maintain stroke volume through ionotropic mechanisms and/or through altered chronotropic mechanisms. The purpose of this study was to identify the interactive effect of age and hyperthermia on cardiac responsiveness to dobutamine-induced cardiac stimulation. Eleven young (26 ± 4 yr) and 8 older (68 ± 5 yr) participants underwent a normothermic and a hyperthermic (baseline core temperature +1.2°C) trial on the same day. In both thermal conditions, after baseline measurements, intravenous dobutamine was administered for 12 min at 5 µg/kg/min, followed by 12 min at 15 µg/kg/min. Primary measurements included echocardiography-based assessments of cardiac function, gastrointestinal and skin temperatures, heart rate, and mean arterial pressure. Heart rate responses to dobutamine were similar between groups in both thermal conditions (P > 0.05). The peak systolic mitral annular velocity (S'), i.e., an index of left ventricular longitudinal systolic function, was similar between groups for both thermal conditions at baseline. While normothermic, the increase in S' between groups was similar with dobutamine administration. However, while hyperthermic, the increase in S' was attenuated in the older participants with dobutamine (P < 0.001). Healthy, older individuals show attenuated inotropic, but maintained chronotropic responsiveness to dobutamine administration during hyperthermia. These data suggest that older individuals have a reduced capacity to increase cardiomyocyte contractility, estimated by changes in S', via ß1-adrenergic mechanisms while hyperthermic.

The effects of vasopressors with and without dobutamine on haemodynamics, metabolism and gut injury during endotoxic shock in rabbits. A controlled study.

INTRODUCTION: Vasopressors increase arterial pressure but they may have deleterious effects on mesenteric blood flow. We aimed to evaluate the response of gut biomarkers and superior mesenteric blood flow to different vasopressors with and without dobutamine. MATERIAL AND METHODS: Thirty New Zealand rabbits were included and randomly allocated to 5 groups: group A - sham group; group B - norepinephrine; group C - norepinephrine plus dobutamine; group D - vasopressin; and group E - vasopressin plus dobutamine. Mean arterial pressure (MAP) target was greater than 60 mmHg. Endotoxic shock was induced by intra-venous injection of lipopolysaccharide (LPS) in four of the five groups. Aortic blood flow (Qao), superior mesenteric artery flow (QSMA) and lactate were measured after LPS injection. Enterocyte damage was evaluated by measurements of serum citrulline and intestinal fatty acid-binding protein (I-FABP) after 4 h. RESULTS: The largest reduction in Qao occurred in group D (64 ± 17.3 to 38 ± 7.5 mL min-1; P = 0.04). QSMA also declined significantly in groups D and E and remained lower than in the other groups over 4 h (group D - baseline: 65 ± 31; 1 h: 37 ± 10; 2 h: 38 ± 10; 3 h: 46 ± 26; and 4 h: 48 ± 15 mL min-1; P < 0.005; group E - baseline: 73 ± 14; 1 h: 28 ± 4.0; 2 h: 37 ± 6.4; 3 h: 40 ± 11; and 4 h: 48 ± 11; P < 0.005; all in mL min-1). Serum citrulline was significantly lower in groups D (P = 0.014) and E (P = 0.019) in comparison to group A. The fluid administration regimen was similar in all groups. CONCLUSIONS: Vasopressin seems to negatively impact gut enterocyte function during endotoxic shock despite the association of an inodilator and adequate fluid replacement.

Venoarterial extracorporeal membrane oxygenation flow or dobutamine to improve microcirculation during ECMO for refractory cardiogenic shock.

PURPOSE: Venoarterial extracorporeal membrane oxygenation (VA ECMO) effectively supports refractory cardiogenic shock (rCS), and sustains macro- and microcirculations. We investigated the respective impact of increasing VA ECMO flow or dobutamine dose on microcirculation in stabilized VA ECMO-treated patients with rCS. METHODS: In this prospective interventional study, we included consecutive intubated patients, with ECMO-supported rCS and hemodynamic stability, able to tolerate stepwise incremental dobutamine doses (from 5 to 20 gamma/kg/min) or ECMO flows (progressive increase by 25% above baseline ECMO flow. Baseline was defined as the lowest VA ECMO flow and dobutamine 5 µg/kg/min (DOBU5) to maintain mean arterial pressure (MAP) ≥ 65 mmHg. Macro- and microcirculations were evaluated after 30 min at each level. RESULTS: Fourteen patients were included. Macro- and microcirculations were assessed 2 [2-5] days post-ECMO onset. Dobutamine-dose increments did not modify any microcirculation parameters. Only the De Backer score tended to be reduced (p = 0.08) by ECMO-flow increments whereas other microcirculation parameters were not affected. These findings did not differ between patients successfully weaned-off ECMO (n = 6) or not. CONCLUSIONS: When macrocirculation has already been restored in patients with ECMO-supported rCS, increasing dobutamine (above 5 µg/kg/min) or ECMO flow did not further improve microcirculation.