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American Journal of Physiology. Heart... Sep 2023We 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...
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. 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.
Topics: Animals; Dogs; Dobutamine; Coronary Stenosis; Myocardium; Heart; Myocardial Ischemia; Coronary Circulation; Myocardial Contraction
PubMed: 37417870
DOI: 10.1152/ajpheart.00735.2022 -
JMIR Research Protocols Nov 2023Breast reconstruction is an integral part of breast cancer care. There are 2 main types of breast reconstruction: alloplastic (using implants) and autologous (using the...
Dobutamine and Goal-Directed Fluid Therapy for Improving Tissue Oxygenation in Deep Inferior Epigastric Perforator (DIEP) Flap Breast Reconstruction Surgery: Protocol for a Randomized Controlled Trial.
BACKGROUND
Breast reconstruction is an integral part of breast cancer care. There are 2 main types of breast reconstruction: alloplastic (using implants) and autologous (using the patient's own tissue). The latter creates a more natural breast mound and avoids the long-term need for surgical revision-more often associated with implant-based surgery. The deep inferior epigastric perforator (DIEP) flap is considered the gold standard approach in autologous breast reconstruction. However, complications do occur with DIEP flap surgery and can stem from poor flap tissue perfusion/oxygenation. Hence, the development of strategies to enhance flap perfusion (eg, goal-directed perioperative fluid therapy) is essential. Current perioperative fluid therapy is traditionally guided by subjective criteria, which leads to wide variations in clinical practice.
OBJECTIVE
The main objective of this trial is to determine whether the use of minimally invasive cardiac output (CO) monitoring for guiding intravenous fluid administration, combined with low-dose dobutamine infusion (via a treatment algorithm), will increase tissue oxygenation in patients undergoing DIEP flap surgery.
METHODS
With appropriate institutional ethics board and Health Canada approval, patients undergoing DIEP flap surgery are randomly assigned to receive CO monitoring for the guidance of intraoperative fluid therapy in addition to a low-dose dobutamine infusion (which potentially improves flap oxygenation) versus the current standard of care. The primary outcome is tissue oxygenation measured via near-infrared spectroscopy at the perfusion zone furthest from the perforator vessels 45 minutes after vascular reanastomosis of the DIEP flap. Low dose (2.5 μg/kg/hr) dobutamine infusion continues for up to 4 hours postoperatively, provided there are no associated complications (ie, persistent tachycardia). Flap oxygenation, hemodynamic parameters, and any medication-associated side effects/complications are monitored for up to 48 hours postoperatively. Complications, rehospitalizations, and patient satisfaction are also collected until 30 days postoperatively.
RESULTS
Funding and regulatory approvals were obtained in 2019, but the study recruitment was interrupted by the COVID-19 pandemic. As of October 4, 2023, 34 participants have been recruited. Because of the significant delays associated with the pandemic, the expected completion date was extended. We expect the study to be completed and ready for potential news release (as appropriate) and publication by July 2024. No patients have suffered any adverse effects/complications from participating in this study, and none have been lost to follow-up.
CONCLUSIONS
CO-directed fluid therapy in combination with a low-dose dobutamine infusion via a treatment algorithm has the potential to improve DIEP flap tissue oxygenation and reduce complications following DIEP flap breast reconstruction surgery. However, given that the investigators remain blinded to group randomization, no comment can be made regarding the efficacy of this intervention for improving tissue oxygenation at this time. Nevertheless, no patients have been withdrawn for safety concerns thus far, and compliance remains high.
TRIAL REGISTRATION
Clinicaltrials.gov NCT04020172; https://clinicaltrials.gov/study/NCT04020172.
PubMed: 37991835
DOI: 10.2196/48576 -
Veterinary Sciences Feb 2024Horses undergoing abdominal exploratory surgery are at risk of hypotension and hypoperfusion. Normal mean arterial pressure is used as a surrogate for adequate tissue...
Horses undergoing abdominal exploratory surgery are at risk of hypotension and hypoperfusion. Normal mean arterial pressure is used as a surrogate for adequate tissue perfusion. However, measures of systemic circulation may not be reflective of microcirculation. This study measured the mean arterial pressure, cardiac index, lactate, and four microcirculatory indices in six healthy, anesthetized adult horses undergoing elective laparotomies. The microcirculatory parameters were measured at three different sites along the gastrointestinal tract (oral mucosa, colonic serosa, and rectal mucosa) with dark-field microscopy. All macro- and microcirculatory parameters were obtained when the horses were normotensive, hypotensive, and when normotension returned following treatment with dobutamine. Hypotension was induced with increases in inhaled isoflurane. The horses successfully induced into hypotension did not demonstrate consistent, expected changes in systemic perfusion or microvascular perfusion parameters at any of the three measured gastrointestinal sites. Normotension was successfully restored with the use of dobutamine, while the systemic perfusion and microvascular perfusion parameters remained relatively unchanged. These findings suggest that the use of mean arterial pressure to make clinical decisions regarding perfusion may or may not be accurate.
PubMed: 38393113
DOI: 10.3390/vetsci11020095 -
Biomedicines Apr 2024Previous studies have shown cardiac abnormalities in acute liver injury, suggesting a potential role in the associated high mortality.
BACKGROUND
Previous studies have shown cardiac abnormalities in acute liver injury, suggesting a potential role in the associated high mortality.
METHODS
We designed an experimental study exploring the short-term effects of acute cholestasis-induced liver injury on cardiac function and structure in a rodent bile duct ligation (BDL) model to elucidate the potential interplay. Thirty-seven male rats were subjected to BDL surgery ( = 28) or served as sham-operated ( = 9) controls. Transthoracic echocardiography, Doppler evaluation of the left anterior descending coronary artery, and myocardial contrast echocardiography were performed at rest and during adenosine and dobutamine stress 5 days after BDL. Immunohistochemical staining of myocardial tissue samples for hypoxia and inflammation as well as serum analysis were performed.
RESULTS
BDL animals exhibited acute liver injury with elevated transaminases, bilirubin, and total circulating bile acids (TBA) 5 days after BDL (TBA control: 0.81 ± 2.54 µmol/L vs. BDL: 127.52 ± 57.03 µmol/L; < 0.001). Concurrently, cardiac function was significantly impaired, characterized by reduced cardiac output (CO) and global longitudinal strain (GLS) in the echocardiography at rest and under pharmacological stress (CO rest control: 120.6 ± 24.3 mL/min vs. BDL 102.5 ± 16.6 mL/min, = 0.041; GLS rest control: -24.05 ± 3.8% vs. BDL: -18.5 ± 5.1%, = 0.01). Myocardial perfusion analysis revealed a reduced myocardial blood flow at rest and a decreased coronary flow velocity reserve (CFVR) under dobutamine stress in the BDL animals (CFVR control: 2.1 ± 0.6 vs. BDL: 1.7 ± 0.5 = 0.047). Immunofluorescence staining indicated myocardial hypoxia and increased neutrophil infiltration.
CONCLUSIONS
In summary, acute cholestasis-induced liver injury can lead to impaired cardiac function mediated by coronary microvascular dysfunction, suggesting that major adverse cardiac events may contribute to the mortality of acute liver failure. This may be due to endothelial dysfunction and direct bile acid signaling.
PubMed: 38672230
DOI: 10.3390/biomedicines12040876 -
Journal of Cardiothoracic and Vascular... Mar 2024The potential risks associated with the use of levosimendan in the pediatric population has not been systematically evaluated. This study aimed to review the available... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The potential risks associated with the use of levosimendan in the pediatric population has not been systematically evaluated. This study aimed to review the available evidence regarding the safety of this treatment.
METHODS
Bio Med Central, PubMed, Embase, and the Cochrane Central Register of clinical trials were searched for studies describing levosimendan administration in the pediatric population in any setting. Relevant studies were independently screened, selected, and their data extracted by two investigators. The authors excluded: reviews, meta-analyses, as well as basic research and trials involving patients >18 years old. The primary outcome was the number and the type of adverse side effects reported during levosimendan administration.
RESULTS
The updated systematic review included 48 studies, enrolling a total of 1,271 pediatric patients who received levosimendan as treatment (790 patients in the 11 studies that reported side effects). The primary adverse effects of levosimendan administration were hypotension and cardiac arrhythmias, particularly tachycardia. Hypotension occurred in approximately 28.9% of patients, while arrhythmia occurred in about 12.3% of patients. Meta analysis of RCTs revealed a rate of all-cause mortality of 2.0% (8 out of 385) in the levosimendan group compared to 3.9% (15 out of 378) in the control group (dobutamine, milrinone or placebo) (risk ratio [RR] = 0.55; 95% confidence interval [CI] = 0.25-1.21; P = 0.14; I = 0%) CONCLUSIONS: Hypotension and cardiac arrhythmia are the most reported side effects of levosimendan in pediatric patients. However, adverse events remain underreported, especially in randomized trials.
Topics: Humans; Child; Adolescent; Simendan; Hydrazones; Pyridazines; Dobutamine; Arrhythmias, Cardiac; Hypotension
PubMed: 38135567
DOI: 10.1053/j.jvca.2023.11.020 -
Hellenic Journal of Cardiology : HJC =... Mar 2024
PubMed: 38453015
DOI: 10.1016/j.hjc.2024.03.007 -
Current Computer-aided Drug Design 2024This study aimed to determine the and effects of some natural and synthetic molecules on acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and α-glucosidase...
INTRODUCTION
This study aimed to determine the and effects of some natural and synthetic molecules on acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and α-glucosidase enzymes.
BACKGROUND
Alzheimer's disease (AD) and Type II diabetes mellitus (T2DM) are considered the most important diseases of today's world. However, the side effects of therapeutic agents used in both diseases limit their use. Therefore, developing drugs with high therapeutic efficacy and better pharmacological profile is important.
OBJECTIVES
This study sets out to determine the related enzyme inhibitors used in treating AD and T2DM, considered amongst the most important diseases of today's world.
METHODS
In the current study, the and effects of dienestrol, hesperetin, Lthyroxine, 3,3',5-Triiodo-L-thyronine (T3) and dobutamine molecules on AChE, BChE and α - glycosidase enzyme activities were investigated.
RESULTS
All the molecules showed an inhibitory effect on the enzymes. The IC and K values of the L-Thyroxine molecule, which showed the strongest inhibition effect for the AChE enzyme, were determined as 1.71 μM and 0.83 ± 0.195 μM, respectively. In addition, dienestrol, T3, and dobutamine molecules showed a more substantial inhibition effect than tacrine. The dobutamine molecule showed the most substantial inhibition effect for the BChE enzyme, and IC and K values were determined as 1.83 μM and 0.845 ± 0.143 μM, respectively. The IC and K values for the hesperetin molecule, which showed the strongest inhibition for the α -glycosidase enzyme, were determined as 13.57 μM and 12.33 ± 2.57 μM, respectively.
CONCLUSION
According to the results obtained, the molecules used in the study may be considered potential inhibitor candidates for AChE, BChE and α-glycosidase.
Topics: Butyrylcholinesterase; Hypoglycemic Agents; Acetylcholinesterase; Humans; Computer Simulation; Cholinesterase Inhibitors; Cholinergic Antagonists; Diabetes Mellitus, Type 2; alpha-Glucosidases; Alzheimer Disease; Molecular Docking Simulation; Glycoside Hydrolase Inhibitors
PubMed: 37202895
DOI: 10.2174/1573409919666230518151414 -
Scientific Reports Apr 2024Although the esophageal stethoscope is used for continuous auscultation during general anesthesia, few studies have investigated phonocardiographic data as a continuous...
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.
Topics: Animals; Swine; Heart Sounds; Dobutamine; Nicardipine; Hemodynamics; Phenylephrine; Propanolamines
PubMed: 38615106
DOI: 10.1038/s41598-024-59362-3 -
Computers in Biology and Medicine Sep 2023Cerebral blood flow (CBF), or perfusion, is a prerequisite for maintaining brain metabolism and normal physiological functions. Diagnosing and evaluating cerebral...
BACKGROUND AND OBJECTIVE
Cerebral blood flow (CBF), or perfusion, is a prerequisite for maintaining brain metabolism and normal physiological functions. Diagnosing and evaluating cerebral perfusion status is crucial to managing brain disease. However, cerebral perfusion imaging devices are complicated to operate, should be controlled by specialized technicians, are often large, and are usually installed in fixed places such as hospitals. It is significantly difficult for clinicians to obtain the cerebral perfusion status in time. Considering that CBF is mainly supplied by the internal carotid artery (ICA), this study proposes a cerebral perfusion status prediction model that can automatically quantify the level of cerebral perfusion in patients by modeling the association between ICA blood flow and cerebral perfusion.
MATERIALS AND METHODS
Forty-eight participants were enrolled in the study after screening. We collected participants' ICA ultrasound and brain magnetic resonance imaging (MRI) data before and after dobutamine injection based on a rigorous experimental paradigm and built an ICA-cerebral perfusion datasetdd. Support vector machine (SVM), k-nearest neighbor (KNN), decision tree (DT), random forest (RF), gradient boosting decision tree (GBDT), and extreme gradient boosting (XGBOOST) were used for early prediction of cerebral perfusion status. The SHAP analysis was adopted to reveal the impact of interpretable predictions for each feature.
RESULTS
The XGBOOST model demonstrated the best overall classification performance with an accuracy of 78.01%, sensitivity of 96.67%, specificity of 98.23%, F1 score of 74.57%, Matthews correlation coefficient (MCC) of 62.17%, and area under the receiver operating characteristic curve (AUC) of 87.08%. Accelerated speed, peak systolic flow velocity, and resistance index of ICA blood flow are important factors for cerebral perfusion prediction.
CONCLUSIONS
The proposed method paves a new avenue for the study of predicting cerebral perfusion status automatically and providesv a noninvasive, real-time, and low-cost alternative to brain perfusion imaging. Moreover, this analysis identifies highly predictive features for the cerebral perfusion status and gives clinicians an intuitive understanding of the influence of key features. The prediction models can serve as an early warning tool that offers sufficient time for clinicians to take early intervention measures.
Topics: Humans; Carotid Artery, Internal; Magnetic Resonance Imaging; Cerebrovascular Circulation; Brain; Machine Learning
PubMed: 37481951
DOI: 10.1016/j.compbiomed.2023.107264 -
Nutrition, Metabolism, and... Nov 2023Hypovitaminosis D is associated with the risk of diabetic complications. Its role in diabetic-related cardiac abnormalities remain poorly understood. We aimed therefore...
BACKGROUND AND AIMS
Hypovitaminosis D is associated with the risk of diabetic complications. Its role in diabetic-related cardiac abnormalities remain poorly understood. We aimed therefore to evaluate the effect of vitamin D deficiency and supplementation on early left ventricular (LV) dysfunction in vitamin D deficient patients with uncomplicated T2D.
METHODS AND RESULTS
Sixty-three consecutive T2D patients who had a diagnosis of vitamin D were prospectively recruited and allocated into 2 groups (25(OH)D < 20 ng/mL: VD >20 ng/mL VD). Twenty-eight of them with 25(OH)D < 20 ng/mL benefited from a 3-month supplementation. At baseline and follow-up, after conventional echocardiography including evaluation of epicardial adipose tissue (EAT), both LV longitudinal (LS) and circumferential (CS) strains and rotation/twist mechanics were evaluated at rest and during dobutamine (DOB) stress. After treatment, T2D patients successfully normalized their 25(OH)D levels. The strongest associations between vitamin D deficiency and supplementation with LV myocardial function were noticed for torsional mechanics indexes under DOB. EAT correlated significantly (p < 0.01) with baseline 25(OH)D and was reduced after supplementation. Significant correlations were obtained between these 2 parameters with twist or apical rotation at baseline (p < 0.01) and between their delta changes at follow-up (p < 0.01) under DOB. Significant improvements in LS and CS (p < 0.05) under DOB were also underlined at follow-up, with major enhancements noticed in the apical region (p < 0.01) of the LV.
CONCLUSIONS
This study provides the first evidences of the potential of vitamin D supplementation as an efficient prophylactic strategy to alleviate the progression of myocardial dysfunction in asymptomatic patients with uncomplicated T2D.
CLINICALTRIALS
NCT03437421.
PubMed: 37543521
DOI: 10.1016/j.numecd.2023.06.017