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Frontiers in Bioscience (Landmark... May 2024Changes in myocardial mitochondrial morphology and function in premature ventricular contractions (PVCs)-induced cardiomyopathy (PVCCM) remain poorly studied. Here, we...
AIMS
Changes in myocardial mitochondrial morphology and function in premature ventricular contractions (PVCs)-induced cardiomyopathy (PVCCM) remain poorly studied. Here, we investigated the effects of PVCs with different coupling intervals (CIs) on myocardial mitochondrial remodelling in a canine model of PVCCM.
METHODS AND RESULTS
Twenty-one beagles underwent pacemaker implantation and were randomised into the sham (n = 7), short-coupled PVCs (SCP, n = 7), and long-coupled PVCs (LCP, n = 7) groups. Right ventricular (RV) apical bigeminy was produced for 12-week to induce PVCCM in the SCP (CI, 250 ms) and LCP (CI, 350 ms) groups. Echocardiography was performed at baseline and biweekly thereafter to evaluate cardiac function. Masson's trichrome staining measured ventricular interstitial fibrosis. The ultrastructural morphology of the myocardial mitochondria was analysed using transmission electron microscopy. Mitochondrial Ca2+ concentration, reactive oxygen species (ROS) levels, adenosine triphosphate (ATP) content, membrane potential, and electron transport chain (ETC) complex activity were measured to assess myocardial mitochondrial function. Twelve-week-PVCs led to left ventricular (LV) enlargement with systolic dysfunction, disrupted mitochondrial morphology, increased mitochondrial Ca2+ concentration and ROS levels, decreased mitochondrial ATP content and membrane potential, and impaired ETC complex activity in both the SCP and LCP groups (all < 0.01 the sham group). Ventricular fibrosis was observed only in canines with LCP. Worse cardiac function and more pronounced abnormalities in mitochondrial morphology and function were observed in the LCP group than to the SCP group (all < 0.05).
CONCLUSION
We demonstrated myocardial mitochondrial abnormalities in dogs with PVCCM, characterised by abnormal mitochondrial morphology, mitochondrial Ca2+ overload, oxidative stress, and impaired mitochondrial energy metabolism. Compared to SCP, long-term LCP exposure resulted in more severe mitochondrial remodelling and cardiac dysfunction in dogs.
Topics: Animals; Dogs; Mitochondria, Heart; Cardiomyopathies; Disease Models, Animal; Ventricular Premature Complexes; Reactive Oxygen Species; Calcium; Male; Adenosine Triphosphate; Membrane Potential, Mitochondrial; Echocardiography
PubMed: 38812311
DOI: 10.31083/j.fbl2905200 -
European Journal of Medical Research May 2024Exosomes (Exos) are involved in the therapeutic effects of bone marrow mesenchymal stem cells (BMSCs) on heart failure (HF). We investigated the molecular mechanisms...
BACKGROUND
Exosomes (Exos) are involved in the therapeutic effects of bone marrow mesenchymal stem cells (BMSCs) on heart failure (HF). We investigated the molecular mechanisms underlying the involvement of BMSC-Exos in ferroptosis on HF.
METHODS
A rat model of HF and cellular model of hypoxia were established. BMSC-Exos were injected into model rats or co-cultured with model cells. In model rats, the cardiac function (echocardiography), oxidative stress (commercial kits), pathological damage (HE staining), fibrosis (MASSON staining), iron deposition (Prussian blue staining), and cell apoptosis (TUNEL staining) were examined. Viability (cell counting kit-8; CCK-8), cell cycle (flow cytometry), oxidative stress, and Fe levels were detected in the model cells. GAS5, UL3, YAP, and TAZ expression were detected using qRT-PCR, western blotting, and immunohistochemistry analyses.
RESULTS
BMSC-Exos restored cardiac function and inhibited oxidative stress, apoptosis, pathological damage, fibrosis, and iron deposition in myocardial tissues of HF rats. In hypoxic cells, BMSC-Exos increased cell viability, decreased the number of G1 phase cells, decreased Fe levels, and inhibited oxidative stress. Ferrostatin-1 (a ferroptosis inhibitor) exhibited a synergistic effect with BMSC-Exos. Additionally, GAS5 was upregulated in BMSC-Exos, further upregulating its target UL3 and Hippo pathway effectors (YAP and TAZ). The relieving effects of BMSC-Exos on HF or hypoxia-induced injury were enhanced by GAS5 overexpression, but weakened by UL3 silencing or verteporfin (a YAP inhibitor).
CONCLUSIONS
GAS5-harbouring BMSC-Exos inhibited ferroptosis by regulating the UL3/Hippo pathway, contributing to HF remission in vivo and in vitro.
Topics: Ferroptosis; Animals; Rats; Heart Failure; Mesenchymal Stem Cells; Exosomes; RNA, Long Noncoding; Male; Hippo Signaling Pathway; Rats, Sprague-Dawley; Protein Serine-Threonine Kinases; Signal Transduction; Oxidative Stress; Apoptosis; Disease Models, Animal
PubMed: 38812041
DOI: 10.1186/s40001-024-01880-x -
Frontiers in Pharmacology 2024Myocardial infarction (MI), the most prevalent ischemic heart disease, constitutes a primary cause of global cardiovascular disease with incidence and mortality. The...
Myocardial infarction (MI), the most prevalent ischemic heart disease, constitutes a primary cause of global cardiovascular disease with incidence and mortality. The pathogenesis of MI is exceedingly intricate, with PANoptosis playing a pivotal role in its pathological process. Xian Ling Gu Bao capsule (XLGB) contains various active components, including flavonoids, terpenes, and phenylpropanoids, and exhibits a wide range of pharmacological activities. However, it remains unclear whether XLGB can protect the myocardium from damage after MI. This study aimed to investigate the impact of XLGB on isoprenaline (ISO)-induced MI in mice and its potential mechanisms. This study assessed the protective effects of XLGB against ISO-induced MI through techniques such as echocardiography, HE staining, Masson staining, and enzyme-linked immunosorbent assay (ELISA). Furthermore, the potential mechanisms of XLGB's protective effects on MI were explored using bioinformatics, molecular docking, and molecular dynamics simulations. These mechanisms were further validated through immunofluorescence staining and Western blotting. The results demonstrated that various doses of XLGB exhibited a significant reduction in myocardial injury induced by myocardial infarction. Intriguingly, higher dosages of XLGB displayed superior therapeutic efficacy compared to the positive control metoprolol. This protective effect is primarily achieved through the inhibition of oxidative stress and the inflammatory processes. Furthermore, we have elucidated that XLGB protected the myocardium from MI-induced damage by suppressing PANoptosis, with a critical role played by the NLRP3/Caspase3/RIP1 signaling pathway. Of particular note, the primary compounds of XLGB were found to directly interact with NLRP3/Caspase3/RIP1, a discovery further validated through molecular docking and molecular dynamics simulations. This suggests that NLRP3/Caspase3/RIP1 may be a therapeutic target for XLGB-induced myocardial protection. In summary, our findings reveal a novel property of XLGB: reverses myocardial damage following MI by inhibiting the NLRP3/Caspase3/RIP1-mediated PANoptosis pathway.
PubMed: 38799163
DOI: 10.3389/fphar.2024.1391511 -
JACC. Cardiovascular Imaging May 2024In patients with low-gradient aortic stenosis (AS) and low transvalvular flow, dobutamine stress echocardiography (DSE) is recommended to determine AS severity, whereas...
BACKGROUND
In patients with low-gradient aortic stenosis (AS) and low transvalvular flow, dobutamine stress echocardiography (DSE) is recommended to determine AS severity, whereas the degree of aortic valve calcification (AVC) supposedly correlates with AS severity according to current European and American guidelines.
OBJECTIVES
The purpose of this study was to assess the relationship between AVC and AS severity as determined using echocardiography and DSE in patients with aortic valve area <1 cm and peak aortic valve velocity <4.0 m/s.
METHODS
All patients underwent DSE to determine AS severity and multislice computed tomography to quantify AVC. Receiver-operating characteristics curve analysis was used to assess the diagnostic value of AVC for AS severity grading as determined using echocardiography and DSE in men and women.
RESULTS
A total of 214 patients were included. Median age was 78 years (25th-75th percentile: 71-84 years) and 25% were women. Left ventricular ejection fraction was reduced (<50%) in 197 (92.1%) patients. Severe AS was diagnosed in 106 patients (49.5%). Moderate AS was diagnosed in 108 patients (50.5%; in 77 based on resting transthoracic echocardiography, in 31 confirmed using DSE). AVC score was high (≥2,000 for men or ≥1,200 for women) in 47 (44.3%) patients with severe AS and in 47 (43.5%) patients with moderate AS. AVC sensitivity was 44.3%, specificity was 56.5%, and positive and negative predictive values for severe AS were 50.0% and 50.8%, respectively. Area under the receiver-operating characteristics curve was 0.508 for men and 0.524 for women.
CONCLUSIONS
Multi-slice computed tomography-derived AVC scores showed poor discrimination between grades of AS severity using DSE and cannot replace DSE in the diagnostic work-up of low-gradient severe AS.
PubMed: 38795109
DOI: 10.1016/j.jcmg.2024.03.014 -
Case report: Successful anesthesia management of noncardiac surgery in a patient with single atrium.Frontiers in Pharmacology 2024Single atrium is very rare congenital cardiac anomaly in adults. The prognosis of patients with single atrium is very poor, with 50% of patients dying owing to...
BACKGROUND
Single atrium is very rare congenital cardiac anomaly in adults. The prognosis of patients with single atrium is very poor, with 50% of patients dying owing to cardiopulmonary complications in childhood. Herein, we focused on anesthesia management for noncardiac surgery in patients with single atrium.
CASE PRESENTATION
A 58-year-old male with a history of bilateral varicocele underwent laparotomy for high-position ligation of the spermatic vein. The patient also had a history of single atrium, atrial fibrillation, chronic heart failure, pulmonary hypertension (PH), and complete right bundle branch block (CRBBB). Given the significant complications associated with general anesthesia in patients with PH, we preferred to use low-dose epidural anesthesia for this patient. Transthoracic echocardiography was used to assess cardiac function before and during surgery and guide perioperative fluid therapy. To limit the stress response, we used a regional nerve block for reducing postoperative pain. Furthermore, we used norepinephrine to appropriately increase the systemic vascular resistance in response to the reduction of systemic vascular resistance caused by epidural anesthesia.
CONCLUSION
Low-dose epidural anesthesia can be safely used in patients with single atrium and PH. The use of perioperative transthoracic echocardiography is helpful in guiding fluid therapy and effectively assessing the cardiac structure and function of patients. Prophylactic administration of norepinephrine before epidural injection may make it easier to maintain the patient's BP.
PubMed: 38756372
DOI: 10.3389/fphar.2024.1370263 -
Journal of the American Society of... May 2024Stress echocardiography (SE) is an important modality in cardiovascular risk stratification and obstructive coronary artery disease (CAD) assessment. Binary sex-based...
BACKGROUND
Stress echocardiography (SE) is an important modality in cardiovascular risk stratification and obstructive coronary artery disease (CAD) assessment. Binary sex-based parameters are classically used for interpretation of these studies, even among transgender women (TGW). CAD is a leading cause of morbidity and mortality in this population. Yet, it remains unclear whether TGW exhibit a distinct stress testing profile from their cisgender counterparts.
METHODS
Using a matched case-control study design, we compared the echocardiographic stress testing profiles of TGW (n=43) with those of matched cisgender men (CGM, n=84) and cisgender women (CGW, n=86) at a single center. Relevant data, including demographics, comorbidities, and cardiac testing data were manually extracted from the patients' charts.
RESULTS
The prevalence of hypertension and dyslipidemia was similar between TGW and CGW and lower than that of CGM (p= .003 and .009, respectively). The majority of comorbidities and lab values were similar. On average, TGW had higher heart rates than CGM (p=.002) and had lower blood pressures than CGM and CGW (p<.05). The TGW's double product and metabolic equivalents were similar to those among CGW and lower than those of CGM (p=.016, p=.018, respectively). On echocardiography, the left ventricular end-diastolic and end-systolic diameters among TGW were similar to those of CGW but lower than CGM's (p=.023, p=.018, respectively). Measures of systolic and diastolic function, except for the exercise mitral valve E:e' ratio which was lower in TGW than CGW (p=.029), were largely similar among the three groups. There was no difference in the wall motion score index, and therefore, no difference in the percentage of positive SE tests.
CONCLUSION
Our study shows, for the first time, that TGW have a SE profile that is distinct from that of their cisgender counterparts. Larger, multicenter, prospective studies are warranted to further characterize the SE profile of TGW.
PubMed: 38754746
DOI: 10.1016/j.echo.2024.05.004 -
BMC Cardiovascular Disorders May 2024The aim of this study is to analyze the diagnostic value of global longitudinal strain (GLS) in detecting inducible myocardial ischemia in patients with chest pain...
INTRODUCTION
The aim of this study is to analyze the diagnostic value of global longitudinal strain (GLS) in detecting inducible myocardial ischemia in patients with chest pain undergoing treadmill contrast-enhanced stress echocardiography (SE).
METHODS
We retrospectively enrolled all patients who underwent invasive coronary angiography after treadmill contrast-enhanced SE. Rest and peak-stress myocardial GLS, segmental LS, and LS of 4-chamber (CH), 2-CH, and 3-CH views were reported. Luminal stenosis of more than 70% or fractional flow reserve (FFR) of < 0.8 was considered significant.
RESULTS
In total 33 patients were included in the final analysis, among whom sixteen patients (48.4%) had significant coronary artery stenosis. Averaged GLS, 3-CH, and 4-CH LS were significantly lower in patients with critical coronary artery stenosis compared to those without significant stenosis (-17.1 ± 7.1 vs. -24.2 ± 7.2, p = 0.041), (-18.2 ± 8.9 vs. -24.6 ± 8.2, p = 0.045) and (-14.8 ± 6.2 vs. -22.8 ± 7.8, p = 0.009), respectively. Receiver operating characteristic (ROC) analysis of ischemic and non-ischemic segments demonstrated that a cut-off value of -20% of stress LS had 71% sensitivity and 60% specificity for ruling out inducible myocardial ischemia (Area under the curve was AUC = 0.72, P < 0.0001).
CONCLUSION
Myocardial LS measured with treadmill contrast-enhanced stress echocardiography demonstrates potential value in identifying patients with inducible myocardial ischemia.
Topics: Humans; Male; Female; Echocardiography, Stress; Retrospective Studies; Middle Aged; Predictive Value of Tests; Aged; Contrast Media; Coronary Stenosis; Coronary Angiography; Reproducibility of Results; Myocardial Contraction; Ventricular Function, Left; Myocardial Ischemia; Fractional Flow Reserve, Myocardial
PubMed: 38750460
DOI: 10.1186/s12872-024-03926-8 -
Scientific Reports May 2024This pilot study focusing on Sickle Cell Anemia (SCA) patients offers a comprehensive and integrative evaluation of respiratory, cardiovascular, hemodynamic, and...
This pilot study focusing on Sickle Cell Anemia (SCA) patients offers a comprehensive and integrative evaluation of respiratory, cardiovascular, hemodynamic, and metabolic variables during exercise. Knowing that diastolic dysfunction is frequent in this population, we hypothesize that a lack of cardiac adaptation through exercise might lead to premature increase in blood lactate concentrations in SCA patients, a potential trigger for acute disease complication. SCA patients were prospectively included in PHYSIO-EXDRE study and underwent a comprehensive stress test with a standardized incremental exercise protocol up to 4 mmol L blood lactate concentration (BL4). Gas exchange, capillary lactate concentration and echocardiography were performed at baseline, during stress test (at ∼ 2 mmol L) and BL4. The population was divided into two groups and compared according to the median value of percentage of theoretical peak oxygen uptake (% ) at BL4. Twenty-nine patients were included (42 ± 12 years old, 48% of women). Most patients reached BL4 at low-intensity exercise [median value of predicted power output (W) was 37%], which corresponds to daily life activities. The median value of % at BL4 was 39%. Interestingly, diastolic maladaptation using echocardiography during stress test along with hemoglobin concentration were independently associated to early occurrence of BL4. As BL4 occurs for low-intensity exercises, SCA patients may be subject to acidosis-related complications even during their daily life activities. Beyond assessing physical capacities, our study underlines that diastolic maladaptation during exercise is associated with an early increase in blood lactate concentration.
Topics: Humans; Anemia, Sickle Cell; Male; Female; Adult; Diastole; Middle Aged; Exercise Tolerance; Exercise Test; Pilot Projects; Echocardiography; Adaptation, Physiological; Lactic Acid; Prospective Studies; Oxygen Consumption; Exercise
PubMed: 38750085
DOI: 10.1038/s41598-024-61689-w -
Journal of Thoracic Disease Apr 2024Blood flow assessment is an emerging technique that allows for assessment of hemodynamics in the heart and blood vessels. Recent advances in cardiovascular imaging... (Review)
Review
BACKGROUND AND OBJECTIVE
Blood flow assessment is an emerging technique that allows for assessment of hemodynamics in the heart and blood vessels. Recent advances in cardiovascular imaging technologies have made it possible for this technique to be more accessible to clinicians and researchers. Blood flow assessment typically refers to two techniques: measurement-based flow visualization using echocardiography or four-dimensional flow magnetic resonance imaging (4D flow MRI), and computer-based flow simulation based on computational fluid dynamics modeling. Using these methods, blood flow patterns can be visualized and quantitative measurements of mechanical stress on the walls of the ventricles and blood vessels, most notably the aorta, can be made. Thus, blood flow assessment has been enhancing the understanding of cardiac and aortic diseases; however, its introduction to clinical practice has been negligible yet. In this article, we aim to discuss the clinical applications and future directions of blood flow assessment in aortic surgery. We then provide our unique perspective on the technique's translational impact on the surgical management of aortic disease.
METHODS
Articles from the PubMed database and Google Scholar regarding blood flow assessment in aortic surgery were reviewed. For the initial search, articles published between 2013 and 2023 were prioritized, including original articles, clinical trials, case reports, and reviews. Following the initial search, additional articles were considered based on manual searches of the references from the retrieved literature.
KEY CONTENT AND FINDINGS
In aortic root pathology and ascending aortic aneurysms, blood flow assessment can elucidate postoperative hemodynamic changes after surgical reconfiguration of the aortic valve complex or ascending aorta. In cases of aortic dissection, analysis of blood flow can predict future aortic dilatation. For complicated congenital aortic anomalies, surgeons may use preoperative imaging to perform "virtual surgery", in which blood flow assessment can predict postoperative hemodynamics for different surgical reconstructions and assist in procedural planning even before entering the operating room.
CONCLUSIONS
Blood flow assessment and computational modeling can evaluate hemodynamics and flow patterns by visualizing blood flow and calculating biomechanical forces in patients with aortic disease. We anticipate that blood flow assessment will become an essential tool in the treatment planning and understanding of the progression of aortic disease.
PubMed: 38738252
DOI: 10.21037/jtd-23-1795 -
Turkish Journal of Haematology :... May 2024Bruton tyrosine kinase inhibition in cardiac tissue causes inhibition of the PI3K-AKT signaling pathway, which is responsible for protecting cardiac tissue during...
OBJECTIVE
Bruton tyrosine kinase inhibition in cardiac tissue causes inhibition of the PI3K-AKT signaling pathway, which is responsible for protecting cardiac tissue during stress. Therefore, there is an increase in the risk of arrhythmia. This study explores the prediction of that risk with the Age-Creatinine-Ejection Fraction (ACEF) score as a simple scoring system based on the components of age, creatinine, and ejection fraction.
MATERIALS AND METHODS
Patients diagnosed with chronic lymphocytic leukemia (CLL) and receiving ibrutinib treatment for at least 1 year were evaluated with echocardiography and Holter electrocardiography and the results were compared with a control group of CLL patients who had not received treatment. ACEF score was calculated with the formula age/left ventricular ejection fraction+1 (if creatinine >2.0 mg/dL).
RESULTS
When the arrhythmia development of the patients was evaluated, no statistically significant difference was found between the control and ibrutinib groups in terms of types of arrhythmias other than paroxysmal atrial fibrillation (PAF). PAF was found to occur at rates of 8% versus 22% (p=0.042) among ibrutinib non-users versus users. For patients using ibrutinib, an ACEF score of >1.21 predicted the development of PAF with 77% sensitivity and 75% specificity (area under the curve: 0.830, 95% confidence interval: 0.698-0.962, p<0.001).
CONCLUSION
The ACEF score can be used as a risk score that predicts the development of PAF in patients diagnosed with CLL who are scheduled to start ibrutinib.
Topics: Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Adenine; Piperidines; Male; Female; Aged; Middle Aged; Arrhythmias, Cardiac; Creatinine; Pyrimidines; Aged, 80 and over; Protein Kinase Inhibitors
PubMed: 38721568
DOI: 10.4274/tjh.galenos.2024.2024.0045