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2.
BMC Cardiovasc Disord ; 24(1): 206, 2024 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-38614990

RESUMO

BACKGROUND: COVID-19 has been associated with cardiac troponin T (cTnT) elevations and changes in cardiac structure and function, but the link between cardiac dysfunction and high-sensitive cardiac troponin T (hs-cTnT) in the acute and convalescent phase is unclear. OBJECTIVE: To assess whether hs-cTnT concentrations are associated with cardiac dysfunction and structural abnormalities after hospitalization for COVID-19, and to evaluate the performance of hs-cTnT to rule out cardiac pathology. METHODS: Patients hospitalized with COVID-19 had hs-cTnT measured during the index hospitalization and after 3-and 12 months, when they also underwent an echocardiographic study. A subset also underwent cardiovascular magnetic resonance imaging (CMR) after 6 months. Cardiac abnormalities were defined as left ventricular hypertrophy or dysfunction, right ventricular dysfunction, or CMR late gadolinium. RESULTS: We included 189 patients with hs-cTnT concentrations measured during hospitalization for COVID-19, and after 3-and 12 months: Geometric mean (95%CI) 13 (11-15) ng/L, 7 (6-8) ng/L and 7 (6-8) ng/L, respectively. Cardiac abnormalities after 3 months were present in 45 (30%) and 3 (8%) of patients with hs-cTnT ≥ and < 5 ng/L at 3 months, respectively (negative predictive value 92.3% [95%CI 88.5-96.1%]). The performance was similar in patients with and without dyspnea. Hs-cTnT decreased from hospitalization to 3 months (more pronounced in intensive care unit-treated patients) and remained unchanged from 3 to 12 months, regardless of the presence of cardiac abnormalities. CONCLUSION: Higher hs-cTnT concentrations in the convalescent phase of COVID-19 are associated with the presence of cardiac pathology and low concentrations (< 5 ng/L) may support in ruling out cardiac pathology following the infection.


Assuntos
COVID-19 , Cardiopatias Congênitas , Humanos , Troponina T , COVID-19/complicações , COVID-19/diagnóstico , Coração , Hipertrofia Ventricular Esquerda
3.
Rev Med Suisse ; 20(869): 744-747, 2024 Apr 10.
Artigo em Francês | MEDLINE | ID: mdl-38616685

RESUMO

The number of elderly people is constantly increasing in Switzerland. This population is often at higher risk of infections and concomitant decompensation of underlying comorbidities, in particular cardiac or respiratory diseases. Vaccines are some of the most effective preventive measures for limiting morbidity and mortality related to some of those infections, such as influenza or shingles. In order to improve vaccination coverage, it is essential to inform the patients of the benefits of vaccination, and to plan a catch-up vaccination consultation. The goal of this article is to offer a practical guide for the general practitioner detailing vaccines for the elderly recommended in Switzerland.


Le nombre de personnes âgées est en constante augmentation en Suisse. Celles-ci sont souvent plus à risque de présenter des infections et de façon concomitante une décompensation de leurs comorbidités, notamment cardiaques et respiratoires. La vaccination est l'une des mesures préventives efficaces pour limiter la morbimortalité associée à certaines de ces infections, comme la grippe ou le zona. Afin d'améliorer la couverture vaccinale, il est primordial d'informer les patients sur les bénéfices de la vaccination et de prévoir une consultation dédiée à une mise à jour vaccinale. Le but de cet article est d'offrir un guide pratique pour le médecin de famille sur les différents vaccins recommandés chez la personne âgée.


Assuntos
Clínicos Gerais , Vacinas contra Influenza , Influenza Humana , Idoso , Humanos , Vacinação , Coração , Influenza Humana/epidemiologia , Influenza Humana/prevenção & controle
5.
Rev Med Suisse ; 20(870): 797-801, 2024 Apr 17.
Artigo em Francês | MEDLINE | ID: mdl-38630040

RESUMO

Adolescence is a vulnerable period for mental health. It is not easy to make a precise diagnosis during this period, as young people may present attenuated forms of psychiatric pathology, or on the contrary, a combination of several types of difficulties. Adopting a transdiagnostic and dimensional approach, based on clinical stages, and thus proposing interventions adapted to the severity of symptoms, is pertinent. As emotional dysregulation lies at the heart of many pathologies, it is a prime target for early intervention. Although interventions for adolescents are still underdeveloped, certain approaches derived from cognitive-behavioral therapies and the psychodynamic current have been adapted for adolescents and appear promising.


L'adolescence constitue une période vulnérable pour la santé mentale. Poser un diagnostic précis durant cette période n'est pas aisé car les jeunes peuvent présenter des formes atténuées de pathologies psychiatriques, ou, au contraire, une combinaison de plusieurs types de difficultés. Adopter une approche transdiagnostique et dimensionnelle, en fonction de stades cliniques, et ainsi proposer des interventions adaptées à la sévérité des symptômes est pertinent. La dysrégulation émotionnelle étant au cœur de nombreuses pathologies, elle est une cible de premier choix pour des interventions précoces. Bien que les interventions pour les adolescents soient encore peu développées, certaines approches issues des thérapies cognitivo-comportementales et du courant psychodynamique ont été adaptées pour les adolescents et semblent prometteuses.


Assuntos
Terapia Cognitivo-Comportamental , Regulação Emocional , Humanos , Adolescente , Coração , Saúde Mental
6.
Int J Mol Sci ; 25(7)2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38612670

RESUMO

We aimed to identify serum exosomal microRNAs (miRNAs) associated with the transition from atrial fibrillation (AF) to sinus rhythm (SR) and investigate their potential as biomarkers for the early recurrence of AF within three months post-treatment. We collected blood samples from eight AF patients at Chang Gung Memorial Hospital in Taiwan both immediately before and within 14 days following rhythm control treatment. Exosomes were isolated from these samples, and small RNA sequencing was performed. Using DESeq2 analysis, we identified nine miRNAs (16-2-3p, 22-3p, 23a-3p, 23b-3p, 125a-5p, 328-3p, 423-5p, 504-5p, and 582-3p) associated with restoration to SR. Further analysis using the DIABLO model revealed a correlation between the decreased expression of miR-125a-5p and miR-328-3p and the early recurrence of AF. Furthermore, early recurrence is associated with a longer duration of AF, presumably indicating a more extensive state of underlying cardiac remodeling. In addition, the reads were mapped to mRNA sequences, leading to the identification of 14 mRNAs (AC005041.1, ARHGEF12, AMT, ANO8, BCL11A, DIO3OS, EIF4ENIF1, G2E3-AS1, HERC3, LARS, NT5E, PITX1, SLC16A12, and ZBTB21) associated with restoration to SR. Monitoring these serum exosomal miRNA and mRNA expression patterns may be beneficial for optimizing treatment outcomes in AF patients.


Assuntos
Fibrilação Atrial , Exossomos , MicroRNAs , Humanos , Fibrilação Atrial/genética , MicroRNAs/genética , Coração , Exossomos/genética , RNA Mensageiro , Anoctaminas
7.
Int J Mol Sci ; 25(7)2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38612740

RESUMO

Tissue fibrosis is characterized by the excessive accumulation of extracellular matrix in various organs, including the lungs, liver, skin, kidneys, pancreas, and heart, ultimately leading to organ failure [...].


Assuntos
Matriz Extracelular , Fígado , Humanos , Morte Celular , Coração , Fibrose
8.
Nutrients ; 16(7)2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38612980

RESUMO

Recently, we reported that during the hypertrophic phase (230 days old) of hereditary cardiomyopathy of the hamster (HCMH), short-term treatment (20 days) with 250 mg/kg/day of taurine prevents the development of hypertrophy in males but not in females. However, the mortality rate in non-treated animals was higher in females than in males. To verify whether the sex-dependency effect of taurine is due to the difference in the disease's progression, we treated the 230-day-old animals for a longer time period of 122 days. Our results showed that long-term treatment with low and high concentrations of taurine significantly prevents cardiac hypertrophy and early death in HCMH males (p < 0.0001 and p < 0.05, respectively) and females (p < 0.01 and p < 0.0001, respectively). Our results demonstrate that the reported sex dependency of short-term treatments with taurine is due to a higher degree of heart remodeling in females when compared to males and not to sex dependency. In addition, sex-dependency studies should consider the differences between the male and female progression of the disease. Thus, long-term taurine therapies are recommended to prevent remodeling and early death in hereditary cardiomyopathy.


Assuntos
Cardiomiopatias , Mortalidade Prematura , Feminino , Masculino , Animais , Cricetinae , Cardiomiopatias/prevenção & controle , Coração , Taurina/farmacologia , Taurina/uso terapêutico , Cardiomegalia/tratamento farmacológico , Cardiomegalia/prevenção & controle
9.
J Cardiothorac Surg ; 19(1): 205, 2024 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-38615019

RESUMO

BACKGROUND: To date, the extended Morrow procedure is considered the gold standard treatment for patients with obstructive hypertrophic cardiomyopathy who experience severe symptoms and are unresponsive to medication treatment. We therefore aimed to perform transapical intramyocardial septal microwave ablation to reduce the thickness of the interventricular septum myocardium in a minimally invasive method. METHODS: Fourteen swine were divided to form either a microwave ablation group (n = 7) or a sham group (n = 7). In the microwave ablation group, a transapical microwave antenna was inserted into the septum to ablate each myocardial segment at 40 W for 1 min, while in the sham group, the same operation was performed but without power output. We used echocardiography, electrocardiogram, during the operation. And added computerized tomography, cardiac nuclear magnetic resonance during follow-up. RESULTS: Segment hypokinesis was observed in all swine immediately following ablation. Compared with the sham group, the thickness of ablated segments in the ablation group decreased significantly 1 month post-operation (ablation group, 5.53 ± 1.00 mm vs. 8.03 ± 1.15 mm, respectively, P < 0.01; sham group, 8.40 ± 0.94 mm vs. 8.21 ± 1.09 mm, respectively, P = 0.081), and the outcome was still observed 1 year post-operation (ablation group, 3.36 ± 0.85 mm vs. 8.03 ± 1.15 mm, respectively, P < 0.01). No perforation of the septum was observed during the procedure or follow-up, and no heart failure or sudden cardiac death occurred during postoperative feeding. CONCLUSIONS: Transapical intramyocardial septal microwave ablation can effectively and safely produce a large region of necrosis. This technique can potentially mimic surgical myectomy while avoiding cardiopulmonary bypass and median sternotomy in high-risk hypertrophic obstructive cardiomyopathy patients.


Assuntos
Cardiomiopatia Hipertrófica , Ablação por Cateter , Humanos , Animais , Suínos , Micro-Ondas/uso terapêutico , Cardiomiopatia Hipertrófica/cirurgia , Coração , Miocárdio
10.
Physiol Rep ; 12(7): e15983, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38605405

RESUMO

Siphons are devices that transport liquids uphill between two containers. It has been proposed that a siphon principle operates in closed circulatory systems, as best exemplified by the circulation of blood in mammals. This principle is supposed to ensure that no additional work is necessary to pump blood above the level of the heart, and that there is no gravitational static pressure gradient in the column of blood. The first statement is correct, while we demonstrate that, ignoring hydraulic resistance to blood flow, the static pressure gradient is equal to the hydrostatic gradient in a siphon model of blood circulation, although the details of the proof do not depend on the geometry of the circulatory system and the proof can be trivially extended to other models such as a vascular waterfall. This implies that the controversy over the siphon principle has no implications for the description of blood circulation, and that mechanisms such as the "baffle," which some authors have appealed to in order to obtain the expected gradient, are not necessary. In our discussion, we also discuss empirical data that appear to provide additional verification of our results, as well as several everyday occurrences that provide additional support.


Assuntos
Coração , Hemodinâmica , Animais , Gravitação , Mamíferos
11.
IEEE J Transl Eng Health Med ; 12: 348-358, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38606390

RESUMO

Wearable sensing has become a vital approach to cardiac health monitoring, and seismocardiography (SCG) is emerging as a promising technology in this field. However, the applicability of SCG is hindered by motion artifacts, including those encountered in practice of which the strongest source is walking. This holds back the translation of SCG to clinical settings. We therefore investigated techniques to enhance the quality of SCG signals in the presence of motion artifacts. To simulate ambulant recordings, we corrupted a clean SCG dataset with real-walking-vibrational noise. We decomposed the signal using several empirical-mode-decomposition methods and the maximum overlap discrete wavelet transform (MODWT). By combining MODWT, time-frequency masking, and nonnegative matrix factorization, we developed a novel algorithm which leveraged the vertical axis accelerometer to reduce walking vibrations in dorsoventral SCG. The accuracy and applicability of our method was verified using heart rate estimation. We used an interactive selection approach to improve estimation accuracy. The best decomposition method for reduction of motion artifact noise was the MODWT. Our algorithm improved heart rate estimation from 0.1 to 0.8 r-squared at -15 dB signal-to-noise ratio (SNR). Our method reduces motion artifacts in SCG signals up to a SNR of -19 dB without requiring any external assistance from electrocardiography (ECG). Such a standalone solution is directly applicable to the usage of SCG in daily life, as a content-rich replacement for other wearables in clinical settings, and other continuous monitoring scenarios. In applications with higher noise levels, ECG may be incorporated to further enhance SCG and extend its usable range. This work addresses the challenges posed by motion artifacts, enabling SCG to offer reliable cardiovascular insights in more difficult scenarios, and thereby facilitating wearable monitoring in daily life and the clinic.


Assuntos
Artefatos , Processamento de Sinais Assistido por Computador , Eletrocardiografia/métodos , Coração , Movimento (Física)
13.
Georgian Med News ; (347): 87-92, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38609120

RESUMO

It was already known that mirabegron, a ß3-adrenoceptor agonist, affected cardiac muscle, data also demonstrated that mirabegron induced a relaxant effect in rat aortic vessels by a mechanism dependent on nitric oxide production. This study examined the possible effects of mirabegron on the coronary vascular tone. Results show that mirabegron induced an acute relaxant effect on coronary segments' contractility, and the relaxation is partly dependent on nitric oxide and K+ channel activation. These findings emphasize the need to consider these mechanisms when translating mirabegron's effects to clinical applications. Mirabegron, the first approved ß3-adrenoceptor agonist, has demonstrated positive effects in heart failure. Research indicates that ß3 agonists induce prompt relaxation in rat aortic and human coronary vessels through a pathway mediated by NO. This study examined mirabegron's influence on bovine coronary segments' contractility. Using isolated tissue baths, the impact of mirabegron on bovine coronary artery segments' contractility was assessed. The plasma level of NO was measured with a specialized kit. NO was determined by measuring plasma nitrite concentrations by spectrophotometric analysis at 540 nm. Mirabegron evoked relaxation in bovine coronary artery segments in a dose-dependent manner. However, this effect was inhibited by the presence of potassium chloride (KCl) (70mM) and methylene blue (30µM). Both potassium channel and NO pathways were found to play a role in the relaxations induced by mirabegron. Furthermore, mirabegron was observed to enhance in vivo nitric oxide (NO) levels, a crucial signaling molecule maintaining cardiovascular equilibrium. Our findings illustrate that mirabegron induces coronary vessel relaxation through the activation of both NO and K+ channels. These findings emphasize the need to consider these mechanisms when translating mirabegron's effects to clinical applications.


Assuntos
Acetanilidas , Coração , Óxido Nítrico , Tiazóis , Humanos , Bovinos , Animais , Ratos , Vasos Coronários , Receptores Adrenérgicos
14.
J Cardiothorac Surg ; 19(1): 202, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38609970

RESUMO

BACKGROUND: The clinical presentation of left ventricular free wall rupture (LVFWR) varies ranging from uneventful condition to congestive heart failure. Here we report two cases of LVFWR with different clinical presentation and notable outcome. A 53-year-old male presenting emergently with signs of myocardial infarction received immediate coronary angiography and thoracic CT-scan showing occlusion of the first marginal coronary branch without possibility of revascularization and minimal pericardial extravasation. Under ICU surveillance, LVFWR occurred 24 h later and was treated by pericardiocentesis and ECMO support followed by immediate uncomplicated surgical repair. Postoperative therapy-refractory vasoplegia and electromechanical dissociation caused fulminant deterioration and the early death of the patient. The second case is a 76-year old male brought to the emergency room after sudden syncope, clinical sings of pericardial tamponade and suspicion of a type A acute aortic dissection. Immediate CT-angiography excluded aortic dissection and revealed massive pericardial effusion and a hypoperfused myocardial area on the territory of the first marginal branch. Immediate sternotomy under mechanical resuscitation enabled removal of the massive intrapericardial clot and revealed LVFWR. After an uncomplicated surgical repair, an uneventful postoperative course, the patient was discharged with sinus rhythm and good biventricular function. One year after the operation, he is living at home, symptom free. DISCUSSION: Whereas the younger patient, who was clinically stable at hospital admission received delayed surgery and did not survive treatment, the older patient, clinically unstable at presentation, went into immediate surgery and had a flawless postoperative course. Thus, early surgical repair of LVFWR leads to best outcome and treating LVFWR as a high emergency regardless of the symptoms improve survival.


Assuntos
Dissecção Aórtica , Doença da Artéria Coronariana , Ruptura Cardíaca , Infarto do Miocárdio , Isquemia Miocárdica , Masculino , Humanos , Idoso , Pessoa de Meia-Idade , Coração
15.
Sensors (Basel) ; 24(7)2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38610445

RESUMO

Cardiovascular diseases pose a long-term risk to human health. This study focuses on the rich-spectrum mechanical vibrations generated during cardiac activity. By combining Fourier series theory, we propose a multi-frequency vibration model for the heart, decomposing cardiac vibration into frequency bands and establishing a systematic interpretation for detecting multi-frequency cardiac vibrations. Based on this, we develop a small multi-frequency vibration sensor module based on flexible polyvinylidene fluoride (PVDF) films, which is capable of synchronously collecting ultra-low-frequency seismocardiography (ULF-SCG), seismocardiography (SCG), and phonocardiography (PCG) signals with high sensitivity. Comparative experiments validate the sensor's performance and we further develop an algorithm framework for feature extraction based on 1D-CNN models, achieving continuous recognition of multiple vibration features. Testing shows that the recognition coefficient of determination (R2), mean absolute error (MAE), and root mean square error (RMSE) of the 8 features are 0.95, 2.18 ms, and 4.89 ms, respectively, with an average prediction speed of 60.18 us/point, meeting the re-quirements for online monitoring while ensuring accuracy in extracting multiple feature points. Finally, integrating the vibration model, sensor, and feature extraction algorithm, we propose a dynamic monitoring system for multi-frequency cardiac vibration, which can be applied to portable monitoring devices for daily dynamic cardiac monitoring, providing a new approach for the early diagnosis and prevention of cardiovascular diseases.


Assuntos
Doenças Cardiovasculares , Vibração , Humanos , Coração , Algoritmos , Fonocardiografia
16.
Sensors (Basel) ; 24(7)2024 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-38610449

RESUMO

Currently, wearable technology is an emerging trend that offers remarkable access to our data through smart devices like smartphones, watches, fitness trackers and textiles. As such, wearable devices can enable health monitoring without disrupting our daily routines. In clinical settings, electrocardiograms (ECGs) and photoplethysmographies (PPGs) are used to monitor heart and respiratory behaviors. In more practical settings, accelerometers can be used to estimate the heart rate when they are attached to the chest. They can also help filter out some noise in ECG signals from movement. In this work, we compare the heart rate data extracted from the built-in accelerometer of a commercial smart pen equipped with sensors (STABILO's DigiPen) to standard ECG monitor readouts. We demonstrate that it is possible to accurately predict the heart rate from the smart pencil. The data collection is carried out with eight volunteers writing the alphabet continuously for five minutes. The signal is processed with a Butterworth filter to cut off noise. We achieve a mean-squared error (MSE) better than 6.685 × 10-3 comparing the DigiPen's computed Δt (time between pulses) with the reference ECG data. The peaks' timestamps for both signals all maintain a correlation higher than 0.99. All computed heart rates (HR =60Δt) from the pen accurately correlate with the reference ECG signals.


Assuntos
Eletrocardiografia , Coração , Humanos , Frequência Cardíaca , Redação , Acelerometria
17.
Sensors (Basel) ; 24(7)2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38610507

RESUMO

In cardiac cine imaging, acquiring high-quality data is challenging and time-consuming due to the artifacts generated by the heart's continuous movement. Volumetric, fully isotropic data acquisition with high temporal resolution is, to date, intractable due to MR physics constraints. To assess whole-heart movement under minimal acquisition time, we propose a deep learning model that reconstructs the volumetric shape of multiple cardiac chambers from a limited number of input slices while simultaneously optimizing the slice acquisition orientation for this task. We mimic the current clinical protocols for cardiac imaging and compare the shape reconstruction quality of standard clinical views and optimized views. In our experiments, we show that the jointly trained model achieves accurate high-resolution multi-chamber shape reconstruction with errors of <13 mm HD95 and Dice scores of >80%, indicating its effectiveness in both simulated cardiac cine MRI and clinical cardiac MRI with a wide range of pathological shape variations.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Aprendizado Profundo , Volume Cardíaco , Coração/diagnóstico por imagem , Artefatos
18.
Sensors (Basel) ; 24(7)2024 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-38610566

RESUMO

INTRODUCTION: Amyotrophic lateral sclerosis (ALS) produces alterations in the autonomic nervous system (ANS), which explains the cardiac manifestations observed in patients. The assessment of heart rate variability (HRV) is what best reflects the activity of the ANS on heart rate. The Polar H7 Bluetooth® device proves to be a non-invasive and much faster technology than existing alternatives for this purpose. OBJECTIVE: The goal of this study is to determine HRV using Polar H7 Bluetooth technology in ALS patients, comparing the obtained measurements with values from healthy individuals. METHOD: The sample consisted of 124 participants: 68 diagnosed with ALS and 56 healthy individuals. Using Polar H7 Bluetooth technology and the ELITE HRV application, various HRV measurements were determined for all participants, specifically the HRV index, RMSSD, RMSSD LN, SDNN index, PNN50, LF, HF, LF/HF ratio, HR average, and HF peak frequency. RESULTS: Statistically significant differences were observed between ALS patients and healthy individuals in the HRV index, RMSSD, RMSSD LN, SDNN index, PNN50, HF, and LF, where healthy individuals exhibited higher scores. For the HR average, the ALS group showed a higher value. Values were similar when comparing men and women with ALS, with only a higher HF peak frequency observed in women. CONCLUSION: The Polar H7 Bluetooth® device is effective in determining heart rate variability alterations in ALS, being a promising prognostic tool for the disease.


Assuntos
Esclerose Amiotrófica Lateral , Masculino , Humanos , Feminino , Frequência Cardíaca , Sistema Nervoso Autônomo , Nível de Saúde , Coração
19.
J Am Heart Assoc ; 13(8): e033628, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38563382

RESUMO

BACKGROUND: The ketone body 3-hydroxybutyrate (3-OHB) increases cardiac output (CO) by 35% to 40% in healthy people and people with heart failure. The mechanisms underlying the effects of 3-OHB on myocardial contractility and loading conditions as well as the cardiovascular effects of its enantiomeric forms, D-3-OHB and L-3-OHB, remain undetermined. METHODS AND RESULTS: Three groups of 8 pigs each underwent a randomized, crossover study. The groups received 3-hour infusions of either D/L-3-OHB (racemic mixture), 100% L-3-OHB, 100% D-3-OHB, versus an isovolumic control. The animals were monitored with pulmonary artery catheter, left ventricle pressure-volume catheter, and arterial and coronary sinus blood samples. Myocardial biopsies were evaluated with high-resolution respirometry, coronary arteries with isometric myography, and myocardial kinetics with D-[11C]3-OHB and L-[11C]3-OHB positron emission tomography. All three 3-OHB infusions increased 3-OHB levels (P<0.001). D/L-3-OHB and L-3-OHB increased CO by 2.7 L/min (P<0.003). D-3-OHB increased CO nonsignificantly (P=0.2). Circulating 3-OHB levels correlated with CO for both enantiomers (P<0.001). The CO increase was mediated through arterial elastance (afterload) reduction, whereas contractility and preload were unchanged. Ex vivo, D- and L-3-OHB dilated coronary arteries equally. The mitochondrial respiratory capacity remained unaffected. The myocardial 3-OHB extraction increased only during the D- and D/L-3-OHB infusions. D-[11C]3-OHB showed rapid cardiac uptake and metabolism, whereas L-[11C]3-OHB demonstrated much slower pharmacokinetics. CONCLUSIONS: 3-OHB increased CO by reducing afterload. L-3-OHB exerted a stronger hemodynamic response than D-3-OHB due to higher circulating 3-OHB levels. There was a dissocitation between the myocardial metabolism and hemodynamic effects of the enantiomers, highlighting L-3-OHB as a potent cardiovascular agent with strong hemodynamic effects.


Assuntos
Hidroxibutiratos , Tomografia Computadorizada por Raios X , Humanos , Suínos , Animais , Ácido 3-Hidroxibutírico/farmacologia , Estudos Cross-Over , Hidroxibutiratos/farmacologia , Coração , Corpos Cetônicos/metabolismo
20.
Biofabrication ; 16(3)2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38574554

RESUMO

The anisotropic organization of cells and the extracellular matrix (ECM) is essential for the physiological function of numerous biological tissues, including the myocardium. This organization changes gradually in space and time, during disease progression such as myocardial infarction. The role of mechanical stimuli has been demonstrated to be essential in obtaining, maintaining and de-railing this organization, but the underlying mechanisms are scarcely known. To enable the study of the mechanobiological mechanisms involved,in vitrotechniques able to spatiotemporally control the multiscale tissue mechanical environment are thus necessary. Here, by using light-sensitive materials combined with light-illumination techniques, we fabricated 2D and 3Din vitromodel systems exposing cells to multiscale, spatiotemporally resolved stiffness anisotropies. Specifically, spatial stiffness anisotropies spanning from micron-sized (cellular) to millimeter-sized (tissue) were achieved. Moreover, the light-sensitive materials allowed to introduce the stiffness anisotropies at defined timepoints (hours) after cell seeding, facilitating the study of their temporal effects on cell and tissue orientation. The systems were tested using cardiac fibroblasts (cFBs), which are known to be crucial for the remodeling of anisotropic cardiac tissue. We observed that 2D stiffness micropatterns induced cFBs anisotropic alignment, independent of the stimulus timing, but dependent on the micropattern spacing. cFBs exhibited organized alignment also in response to 3D stiffness macropatterns, dependent on the stimulus timing and temporally followed by (slower) ECM co-alignment. In conclusion, the developed model systems allow improved fundamental understanding of the underlying mechanobiological factors that steer cell and ECM orientation, such as stiffness guidance and boundary constraints.


Assuntos
Matriz Extracelular , Engenharia Tecidual , Engenharia Tecidual/métodos , Miocárdio , Coração , Fibroblastos
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