Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 28.030
Filtrar
1.
Nat Commun ; 12(1): 5192, 2021 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-34465780

RESUMO

Despite progressive improvements over the decades, the rich temporally resolved data in an echocardiogram remain underutilized. Human assessments reduce the complex patterns of cardiac wall motion, to a small list of measurements of heart function. All modern echocardiography artificial intelligence (AI) systems are similarly limited by design - automating measurements of the same reductionist metrics rather than utilizing the embedded wealth of data. This underutilization is most evident where clinical decision making is guided by subjective assessments of disease acuity. Predicting the likelihood of developing post-operative right ventricular failure (RV failure) in the setting of mechanical circulatory support is one such example. Here we describe a video AI system trained to predict post-operative RV failure using the full spatiotemporal density of information in pre-operative echocardiography. We achieve an AUC of 0.729, and show that this ML system significantly outperforms a team of human experts at the same task on independent evaluation.


Assuntos
Aprendizado Profundo , Insuficiência Cardíaca/diagnóstico por imagem , Disfunção Ventricular Direita/cirurgia , Ecocardiografia , Coração/diagnóstico por imagem , Coração/fisiopatologia , Insuficiência Cardíaca/fisiopatologia , Humanos , Período Pós-Operatório , Cuidados Pré-Operatórios , Estudos Retrospectivos , Disfunção Ventricular Direita/diagnóstico por imagem , Disfunção Ventricular Direita/fisiopatologia , Gravação em Vídeo
2.
Sci Rep ; 11(1): 17798, 2021 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-34493765

RESUMO

There is increasing evidence of cardiac involvement post-SARS-CoV-2 infections in symptomatic as well as in oligo- and asymptomatic athletes. This study aimed to characterize the possible early effects of SARS-CoV-2 infections on myocardial morphology and cardiopulmonary function in athletes. Eight male elite handball players (27 ± 3.5 y) with past SARS-CoV-2 infection were compared with four uninfected teammates (22 ± 2.6 y). Infected athletes were examined 19 ± 7 days after the first positive PCR test. Echocardiographic assessment of the global longitudinal strain under resting conditions was not significantly changed (- 17.7% vs. - 18.1%). However, magnetic resonance imaging showed minor signs of acute inflammation/oedema in all infected athletes (T2-mapping: + 4.1 ms, p = 0.034) without reaching the Lake-Louis criteria. Spiroergometric analysis showed a significant reduction in VO2max (- 292 ml/min, - 7.0%), oxygen pulse (- 2.4 ml/beat, - 10.4%), and respiratory minute volume (VE) (- 18.9 l/min, - 13.8%) in athletes with a history of SARS-CoV2 infection (p < 0.05, respectively). The parameters were unchanged in the uninfected teammates. SARS-CoV2 infection caused impairment of cardiopulmonary performance during physical effort in elite athletes. It seems reasonable to screen athletes after SARS-CoV2 infection with spiroergometry to identify performance limitations and to guide the return to competition.


Assuntos
Atletas/estatística & dados numéricos , Desempenho Atlético/estatística & dados numéricos , COVID-19/fisiopatologia , Coração/fisiopatologia , Pulmão/fisiopatologia , Adulto , Infecções Assintomáticas , Desempenho Atlético/fisiologia , COVID-19/diagnóstico , COVID-19/virologia , Teste de Ácido Nucleico para COVID-19/estatística & dados numéricos , Ecocardiografia/estatística & dados numéricos , Teste de Esforço/estatística & dados numéricos , Alemanha , Coração/diagnóstico por imagem , Humanos , Pulmão/diagnóstico por imagem , Imageamento por Ressonância Magnética , Masculino , RNA Viral/isolamento & purificação , Estudos Retrospectivos , SARS-CoV-2/isolamento & purificação , SARS-CoV-2/patogenicidade , Espirometria/estatística & dados numéricos , Adulto Jovem
3.
Nutrients ; 13(7)2021 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-34371977

RESUMO

The effectiveness of weight loss treatment displays dramatic inter-individual variabilities, even with well-controlled energy intake/expenditure. This study aimed to determine the association between daily rhythms of cardiac autonomic control and weight loss efficiency and to explore the potential relevance to weight loss resistance in humans carrying the genetic variant C at CLOCK 3111T/C. A total of 39 overweight/obese Caucasian women (20 CLOCK 3111C carriers and 19 non-carriers) completed a behaviour-dietary obesity treatment of ~20 weeks, during which body weight was assessed weekly. Ambulatory electrocardiographic data were continuously collected for up to 3.5 days and used to quantify the daily rhythm of fractal cardiac dynamics (FCD), a non-linear measure of autonomic function. FCD showed a 24 h rhythm (p < 0.001). Independent of energy intake and physical activity level, faster weight loss was observed in individuals with the phase (peak) of the rhythm between ~2-8 p.m. and with a larger amplitude. Interestingly, the phase effect was significant only in C carriers (p = 0.008), while the amplitude effect was only significant in TT carriers (p < 0.0001). The daily rhythm of FCD and CLOCK 3111T/C genotype is linked to weight loss response interactively, suggesting complex interactions between the genetics of the circadian clock, the daily rhythm of autonomic control, and energy balance control.


Assuntos
Sistema Nervoso Autônomo/fisiopatologia , Proteínas CLOCK/genética , Ritmo Circadiano/genética , Coração/inervação , Sobrepeso/terapia , Perda de Peso/genética , Adulto , Estudos de Casos e Controles , Ritmo Circadiano/fisiologia , Eletrocardiografia Ambulatorial , Ingestão de Energia , Exercício Físico , Feminino , Fractais , Genótipo , Coração/fisiopatologia , Humanos , Pessoa de Meia-Idade , Obesidade/genética , Obesidade/fisiopatologia , Obesidade/terapia , Sobrepeso/genética , Sobrepeso/fisiopatologia , Polimorfismo de Nucleotídeo Único/genética
4.
Int J Mol Sci ; 22(16)2021 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-34445106

RESUMO

Tissue decellularization is typically assessed through absorbance-based DNA quantification after tissue digestion. This method has several disadvantages, namely its destructive nature and inadequacy in experimental situations where tissue is scarce. Here, we present an image processing algorithm for quantitative analysis of DNA content in (de)cellularized tissues as a faster, simpler and more comprehensive alternative. Our method uses local entropy measurements of a phase contrast image to create a mask, which is then applied to corresponding nuclei labelled (UV) images to extract average fluorescence intensities as an estimate of DNA content. The method can be used on native or decellularized tissue to quantify DNA content, thus allowing quantitative assessment of decellularization procedures. We confirm that our new method yields results in line with those obtained using the standard DNA quantification method and that it is successful for both lung and heart tissues. We are also able to accurately obtain a timeline of decreasing DNA content with increased incubation time with a decellularizing agent. Finally, the identified masks can also be applied to additional fluorescence images of immunostained proteins such as collagen or elastin, thus allowing further image-based tissue characterization.


Assuntos
Engenharia Tecidual/métodos , Tecidos Suporte/química , Animais , Colágeno/metabolismo , DNA/metabolismo , Elastina/metabolismo , Matriz Extracelular/metabolismo , Coração/fisiopatologia , Pulmão/metabolismo
5.
Medicine (Baltimore) ; 100(30): e26431, 2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34397684

RESUMO

BACKGROUND: Sodium glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide 1 receptor agonists (GLP-1 RAs) have been demonstrated to be able to improve the cardiovascular and renal prognosis in patients with type 2 diabetes (T2D). However, the relative efficacy of various SGLT2 inhibitors and GLP-1 RAs on cardiorenal outcomes is unestablished. METHODS: We searched PubMed and Embase for relevant cardiovascular or renal outcome trials (CVOTs). Endpoints of interest were major adverse cardiovascular events (MACE), stroke, myocardial infarction (MI), cardiovascular death (CVD), all-cause death (ACD), kidney function progression (KFP), and hospitalization for heart failure (HHF). Bayesian network meta-analysis was conducted to produce pooled hazard ratio (HR) and 95% confidence interval (CI). We calculated the probability values of surface under the cumulative ranking curve to rank active and placebo interventions. RESULTS: Fourteen COVTs were included in analysis. Sotagliflozin (HR 0.76, 95% CI 0.61-0.94), subcutaneous semaglutide, and albiglutide lowered MACE versus lixisenatide among others. Sotagliflozin (HR 0.59, 95% CI 0.40-0.89), canagliflozin, and empagliflozin lowered HHF versus subcutaneous semaglutide among others. Dapagliflozin and empagliflozin lowered KFP versus exenatide among others. Empagliflozin and oral semaglutide lowered CVD versus dapagliflozin among others. Sotagliflozin (HR 0.65, 95% CI 0.47-0.91) and albiglutide lowered MI versus ertugliflozin among others. Sotagliflozin (HR 0.56, 95% CI 0.37-0.85) and subcutaneous semaglutide lowered stroke versus empagliflozin among others. Oral semaglutide and empagliflozin lowered ACD versus subcutaneous semaglutide among others. The maximum surface under the cumulative ranking curve values followed sotagliflozin, subcutaneous semaglutide, and albiglutide in lowering MACE; sotagliflozin, canagliflozin, and empagliflozin in lowering HHF; dapagliflozin and empagliflozin in lowering KFP; empagliflozin and oral semaglutide in lowering CVD; sotagliflozin and albiglutide in lowering MI; sotagliflozin and subcutaneous semaglutide in lowering stroke; and oral semaglutide and empagliflozin in lowering ACD. CONCLUSIONS: This updated network meta-analysis reproduced the findings in the first network meta-analysis, and moreover revealed that sotagliflozin was one of the most effective drugs as for lowering MI, stroke, MACE, and HHF, whereas ertugliflozin was not. These findings will provide the according evidence regarding the usage of specific SGLT2 inhibitors and GLP-1 RAs in T2D patients for prevention of specific cardiorenal endpoints.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Receptor do Peptídeo Semelhante ao Glucagon 1/antagonistas & inibidores , Coração/efeitos dos fármacos , Rim/efeitos dos fármacos , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Diabetes Mellitus Tipo 2/fisiopatologia , Receptor do Peptídeo Semelhante ao Glucagon 1/uso terapêutico , Coração/fisiopatologia , Humanos , Rim/fisiopatologia , Metanálise em Rede , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Resultado do Tratamento
6.
Physiol Rep ; 9(17): e14998, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34448551

RESUMO

The spread of the novel coronavirus 2019 (COVID-19) has caused a global pandemic. The disease has spread rapidly, and research shows that COVID-19 can induce long-lasting cardiac damage. COVID-19 can result in elevated cardiac biomarkers indicative of acute cardiac injury, and research utilizing echocardiography has shown that there is mechanical dysfunction in these patients as well, especially when observing the isovolumic, systolic, and diastolic portions of the cardiac cycle. The purpose of this study was to present two case studies on COVID-19 positive patients who had their cardiac mechanical function assessed every day during the acute period to show that cardiac function in these patients was altered, and the damage occurring can change from day-to-day. Participant 1 showed compromised cardiac function in the systolic time, diastolic time, isovolumic time, and the calculated heart performance index (HPI), and these impairments were sustained even 23 days post-symptom onset. Furthermore, Participant 1 showed prolonged systolic periods that lasted longer than the diastolic periods, indicative of elevated pulmonary artery pressure. Participant 2 showed decreases in systole and consequently, increases in HPI during the 3 days post-symptom onset, and these changes returned to normal after day 4. These results showed that daily observation of cardiac function can provide detailed information about the overall mechanism by which cardiac dysfunction is occurring and that COVID-19 can induce cardiac damage in unique patterns and thus can be studied on a case-by-case basis, day-to-day during infection. This could allow us to move toward more personalized cardiovascular medical treatment.


Assuntos
COVID-19/fisiopatologia , Cardiopatias/fisiopatologia , Coração/fisiopatologia , Hemodinâmica , SARS-CoV-2/patogenicidade , Função Ventricular , Adulto , COVID-19/diagnóstico , COVID-19/virologia , Técnicas de Diagnóstico Cardiovascular/instrumentação , Coração/virologia , Cardiopatias/diagnóstico , Cardiopatias/virologia , Interações Hospedeiro-Patógeno , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Fatores de Tempo , Transdutores
7.
Theranostics ; 11(16): 7984-7994, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34335975

RESUMO

Rationale: Acute myocardial infarction (MI) triggers a systemic inflammatory response including crosstalk along the heart-kidney axis. We employed radionuclide-based inflammation-targeted whole-body molecular imaging to identify potential cardio-renal crosstalk after MI in a translational setup. Methods: Serial whole-body positron emission tomography (PET) with the specific CXCR4 ligand 68Ga-Pentixafor was performed after MI in mice. Tracer retention in kidneys and heart was compared to hematopoietic organs to evaluate systemic inflammation, validated by ex vivo analysis and correlated with progressive contractile dysfunction. Additionally, 96 patients underwent 68Ga-Pentixafor PET within the first week after MI, for systems-based image analysis and to determine prognostic value for adverse renal outcome. Results: In mice, transient myocardial CXCR4 upregulation occurred early after MI. Cardiac and renal PET signal directly correlated over the time course (r = 0.62, p < 0.0001), suggesting an inflammatory link between organs. Ex-vivo autoradiography (r = 0.9, p < 0.01) and CD68 immunostaining indicated signal localization to inflammatory cell content. Renal signal at 7d was inversely proportional to left ventricular ejection fraction at 6 weeks after MI (r = -0.79, p < 0.01). In patients, renal CXCR4 signal also correlated with signal from infarct (r = 0.25, p < 0.05) and remote myocardium (r = 0.39, p < 0.0001). Glomerular filtration rate (GFR) was available in 48/96 (50%) during follow-up. Worsening of renal function (GFR loss >5 mL/min/1.73m2), occurred a mean 80.5 days after MI in 16/48 (33.3%). Kaplan-Meier analysis revealed adverse renal outcome for patients with elevated remote myocardial CXCR4 signal (p < 0.05). Multivariate Cox analysis confirmed an independent predictive value (relative to baseline GFR, LVEF, infarct size; HR, 5.27). Conclusion: Systems-based CXCR4-targeted molecular imaging identifies inflammatory crosstalk along the cardio-renal axis early after MI.


Assuntos
Coração/fisiopatologia , Rim/fisiopatologia , Infarto do Miocárdio/fisiopatologia , Animais , Complexos de Coordenação/farmacologia , Humanos , Inflamação/metabolismo , Inflamação/fisiopatologia , Masculino , Camundongos , Imagem Molecular/métodos , Infarto do Miocárdio/metabolismo , Miocárdio/metabolismo , Peptídeos Cíclicos/farmacologia , Tomografia por Emissão de Pósitrons/métodos , Receptores CXCR4/metabolismo , Volume Sistólico , Função Ventricular Esquerda , Remodelação Ventricular/fisiologia , Imagem Corporal Total/métodos
8.
Open Heart ; 8(2)2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34376573

RESUMO

OBJECTIVES: To describe the use of echocardiography in patients hospitalised with suspected coronavirus infection and to assess its impact on clinical management. METHODS: We studied 79 adults from a prospective registry of inpatients with suspected coronavirus infection at a single academic centre. Echocardiographic indications included abnormal biomarkers, shock, cardiac symptoms, arrhythmia, worsening hypoxaemia or clinical deterioration. Study type (limited or complete) was assessed for each patient. The primary outcome measure was echocardiography-related change in clinical management, defined as intensive care transfer, medication changes, altered ventilation parameters or subsequent cardiac procedures within 24 hours of echocardiography. Coronavirus-positive versus coronavirus-negative patient groups were compared. The relationship between echocardiographic findings and coronavirus mortality was assessed. RESULTS: 56 patients were coronavirus-positive and 23 patients were coronavirus-negative with symptoms attributed to other diagnoses. Coronavirus-positive patients more often received limited echocardiograms (70% vs 26%, p=0.001). The echocardiographic indication for coronavirus-infected patients was frequently worsening hypoxaemia (43% vs 4%) versus chest pain, syncope or clinical heart failure (23% vs 44%). Echocardiography changed management less frequently in coronavirus-positive patients (18% vs 48%, p=0.01). Among coronavirus-positive patients, 14 of 56 (25.0%) died during hospitalisation. Those who died more often had echocardiography to evaluate clinical deterioration (71% vs 24%) and had elevated right ventricular systolic pressures (37 mm Hg vs 25 mm Hg), but other parameters were similar to survivors. CONCLUSIONS: Echocardiograms performed on hospitalised patients with coronavirus infection were often technically limited, and their findings altered patient management in a minority of patients.


Assuntos
COVID-19/diagnóstico por imagem , Ecocardiografia Doppler , Cardiopatias/diagnóstico por imagem , Coração/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , COVID-19/fisiopatologia , COVID-19/terapia , COVID-19/virologia , Tomada de Decisão Clínica , Feminino , Coração/fisiopatologia , Coração/virologia , Cardiopatias/fisiopatologia , Cardiopatias/terapia , Cardiopatias/virologia , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos
9.
Molecules ; 26(13)2021 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-34206441

RESUMO

DJ-1 was originally identified as an oncogene product while mutations of the gene encoding DJ-1/PARK7 were later associated with a recessive form of Parkinson's disease. Its ubiquitous expression and diversity of function suggest that DJ-1 is also involved in mechanisms outside the central nervous system. In the last decade, the contribution of DJ-1 to the protection from ischemia-reperfusion injury has been recognized and its involvement in the pathophysiology of cardiovascular disease is attracting increasing attention. This review describes the current and gaps in our knowledge of DJ-1, focusing on its role in regulating cardiovascular function. In parallel, we present original data showing an association between increased DJ-1 expression and antiapoptotic and anti-inflammatory markers following cardiac and vascular surgical procedures. Future studies should address DJ-1's role as a plausible novel therapeutic target for cardiovascular disease.


Assuntos
Coração/fisiopatologia , Traumatismo por Reperfusão Miocárdica , Miocárdio , Proteína Desglicase DJ-1/metabolismo , Animais , Biomarcadores/metabolismo , Humanos , Inflamação/metabolismo , Inflamação/patologia , Inflamação/fisiopatologia , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/patologia , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Miocárdio/metabolismo , Miocárdio/patologia
10.
Cardiovasc Toxicol ; 21(10): 781-789, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34255300

RESUMO

Since the onset of the global COVID-19 pandemic, there has been much discussion about the advantages and disadvantages of ongoing chronic drug therapies in SARS-CoV-2-positive patients. These discussions include also statins treatment. The statins are among the most widely used drugs in the global population. Statins aim to lower cholesterol, which is essential for many biological processes but can lead to heart disease if levels are too high; however, also the pleiotropic effects of statins are well known. So could the anti-inflammatory or the potential antiviral effects of statins be helpful in avoiding extreme inflammation and severity in COVID-19? To date, there are conflicting opinions on the effects of statins in the course of COVID-19 infection. The aim of this article is to describe the molecular and pharmacological basis of the pleiotropic effects of statins that could be more involved in the fight against COVID-19 infection and to investigate the current epidemiological evidence in the literature on the current and important topic.


Assuntos
Anti-Inflamatórios/uso terapêutico , Antivirais/uso terapêutico , COVID-19/tratamento farmacológico , Cardiopatias/tratamento farmacológico , Coração/efeitos dos fármacos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , SARS-CoV-2/efeitos dos fármacos , Animais , Anti-Inflamatórios/efeitos adversos , Antivirais/efeitos adversos , COVID-19/epidemiologia , COVID-19/fisiopatologia , COVID-19/virologia , Coração/fisiopatologia , Coração/virologia , Cardiopatias/epidemiologia , Cardiopatias/fisiopatologia , Cardiopatias/virologia , Interações Hospedeiro-Patógeno , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , SARS-CoV-2/patogenicidade , Resultado do Tratamento
11.
Am J Physiol Regul Integr Comp Physiol ; 321(3): R385-R395, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34259041

RESUMO

Exercise intolerance is a hallmark symptom of cardiovascular disease and likely occurs via enhanced activation of muscle metaboreflex-induced vasoconstriction of the heart and active skeletal muscle which, thereby limits cardiac output and peripheral blood flow. Muscle metaboreflex vasoconstrictor responses occur via activation of metabolite-sensitive afferent fibers located in ischemic active skeletal muscle, some of which express transient receptor potential vanilloid 1 (TRPV1) cation channels. Local cardiac and intrathecal administration of an ultrapotent noncompetitive, dominant negative agonist resiniferatoxin (RTX) can ablate these TRPV1-sensitive afferents. This technique has been used to attenuate cardiac sympathetic afferents and nociceptive pain. We investigated whether intrathecal administration (L4-L6) of RTX (2 µg/kg) could chronically attenuate subsequent muscle metaboreflex responses elicited by reductions in hindlimb blood flow during mild exercise (3.2 km/h) in chronically instrumented conscious canines. RTX significantly attenuated metaboreflex-induced increases in mean arterial pressure (27 ± 5.0 mmHg vs. 6 ± 8.2 mmHg), cardiac output (1.40 ± 0.2 L/min vs. 0.28 ± 0.1 L/min), and stroke work (2.27 ± 0.2 L·mmHg vs. 1.01 ± 0.2 L·mmHg). Effects were maintained until 78 ± 14 days post-RTX at which point the efficacy of RTX injection was tested by intra-arterial administration of capsaicin (20 µg/kg). A significant reduction in the mean arterial pressure response (+45.7 ± 6.5 mmHg pre-RTX vs. +19.7 ± 3.1 mmHg post-RTX) was observed. We conclude that intrathecal administration of RTX can chronically attenuate the muscle metaboreflex and could potentially alleviate enhanced sympatho-activation observed in cardiovascular disease states.


Assuntos
Débito Cardíaco/efeitos dos fármacos , Diterpenos/farmacologia , Membro Posterior/efeitos dos fármacos , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Animais , Pressão Arterial/efeitos dos fármacos , Débito Cardíaco/fisiologia , Diterpenos/administração & dosagem , Cães , Coração/efeitos dos fármacos , Coração/fisiopatologia , Membro Posterior/fisiopatologia , Isquemia/fisiopatologia , Contração Muscular/efeitos dos fármacos , Contração Muscular/fisiologia , Fluxo Sanguíneo Regional/efeitos dos fármacos , Sistema Nervoso Simpático/efeitos dos fármacos , Sistema Nervoso Simpático/fisiopatologia , Vasoconstrição/fisiologia
12.
Am J Physiol Regul Integr Comp Physiol ; 321(3): R338-R351, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34259047

RESUMO

Defined as a structural or functional cardiac abnormality accompanied by symptoms, signs, or biomarkers of altered ventricular pressures or volumes, heart failure also is a state of autonomic disequilibrium. A large body of evidence affirms that autonomic disturbances are intrinsic to heart failure; basal or stimulated sympathetic nerve firing or neural norepinephrine (NE) release more often than not exceed homeostatic need, such that an initially adaptive adrenergic or vagal reflex response becomes maladaptive. The magnitude of such maladaptation predicts prognosis. This Ludwig lecture develops two theses: the elucidation and judiciously targeted amelioration of maladaptive autonomic disturbances offers opportunities to complement contemporary guideline-based heart failure therapy, and serendipitous single-participant insights, acquired in the course of experimental protocols with entirely different intent, can generate novel insight, inform mechanisms, and launch entirely new research directions. I précis six elements of our current synthesis of the causes and consequences of maladaptive sympathetic disequilibrium in heart failure, shaped by patient-inspired epiphanies: arterial baroreceptor reflex modulation, excitation stimulated by increased cardiac filling pressure, paradoxical muscle sympathetic activation as a peripheral neurogenic constraint on exercise capacity, renal sympathetic restraint of natriuresis, coexisting sleep apnea, and augmented chemoreceptor reflex sensitivity and then conclude by envisaging translational therapeutic opportunities.


Assuntos
Sistema Nervoso Autônomo/fisiopatologia , Insuficiência Cardíaca/fisiopatologia , Coração/inervação , Sistema Nervoso Simpático/fisiopatologia , Exercício Físico/fisiologia , Coração/fisiopatologia , Humanos , Reflexo/fisiologia
13.
Life Sci ; 282: 119815, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34256040

RESUMO

AIM: An adverse side-effect of Liraglutide (LG), a Glucagon-Like Peptide 1 (GLP1)-analog commonly used in treatments for diabetes, is positive chronotropy. The goal of this study is to investigate on the mechanism of this drug-induced chronotropy and explore potential means to mitigate this side-effect so as to maximize the therapeutic benefits from LG. MAIN METHODS: Experiments were conducted with: 1) Isolated rabbit hearts in a Langendorff set-up to assess for direct effects of drug actions and 2) Murine cardiomyocytes isolated from the sino-atrial node (SAN) to assess the effects of LG on spontaneous action potential (AP) firing and the hyperpolarization-activated current If. KEY FINDINGS: LG induced a dose-dependent increase in heart rate. Its effects on sinus node automaticity, which were not suppressed during ß-blockade with Propranolol, were abolished by If blockade with Ivabradine. In isolated murine SAN myocytes, LG increased spontaneous AP firing frequency by an increase in diastolic depolarization slope without changing other electrophysiological parameters. SIGNIFICANCE: LG-induced positive chronotropy is partly due to a direct effect on the SAN and is independent of the adrenergic cascade and extrinsic autonomic reflex mechanisms. The direct LG-associated increase in heart rate should be mitigated with If blockers rather than ß-blockade.


Assuntos
Potenciais de Ação/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Coração/fisiopatologia , Liraglutida , Miocárdio/metabolismo , Miócitos Cardíacos/metabolismo , Animais , Liraglutida/efeitos adversos , Liraglutida/farmacologia , Masculino , Camundongos , Coelhos
14.
Life Sci ; 282: 119761, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34217764

RESUMO

AIMS: Eugenol is a natural compound found in the essential oils of many aromatic plants. The compound is used as a local anesthetic because of its inhibitory effect on the voltage-gated Na+ channels (Nav), which are expressed in the nociceptive neurons. Eugenol has shown wide range of activities in the cardiovascular system; most of these activities are attributed to the modulation of voltage-sensitive Ca2+ channels. However, its action on Nav1.5, the main subtype of Nav expressed in the mammalian myocardium, is unknown. The interaction of eugenol with Nav1.5 could also contribute to its antiarrhythmic properties in vitro and ex vivo. We investigated the compound's effect on sodium current (INa) and its possible cardiac antiarrhythmic activity. METHODS: The effect of eugenol on cardiac contractility was investigated using isolated atrium from guinea pig (for isometric force measurements). The compound's effect on INa was evaluated using human embryonic cell transiently expressing human Nav1.5 and patch-clamp technique. KEY FINDINGS: Eugenol caused negative inotropic and chronotropic effects in the atria. In the ex vivo arrhythmia model, eugenol decreased atrial pacing disturbance induced by ouabain. Eugenol reduced the INa in a concentration-dependent manner. Furthermore, the compound left-shifted the stationary inactivation curve, delayed recovery from inactivation of the INa, and preferentially blocked the channel in the inactivated state. Importantly, eugenol was able to attenuate the late sodium current. All these aspects are considered to be antiarrhythmic. SIGNIFICANCE: Overall, our findings demonstrate that eugenol has antiarrhythmic activity due, at least in part, to its interaction with Nav1.5.


Assuntos
Antiarrítmicos/uso terapêutico , Arritmias Cardíacas/tratamento farmacológico , Eugenol/uso terapêutico , Coração/efeitos dos fármacos , Canal de Sódio Disparado por Voltagem NAV1.5/metabolismo , Animais , Arritmias Cardíacas/metabolismo , Arritmias Cardíacas/fisiopatologia , Feminino , Cobaias , Células HEK293 , Coração/fisiopatologia , Humanos , Masculino , Técnicas de Patch-Clamp
15.
Nat Commun ; 12(1): 4501, 2021 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-34301958

RESUMO

Nitric oxide (NO) is a short-lived signaling molecule that plays a pivotal role in cardiovascular system. Organic nitrates represent a class of NO-donating drugs for treating coronary artery diseases, acting through the vasodilation of systemic vasculature that often leads to adverse effects. Herein, we design a nitrate-functionalized patch, wherein the nitrate pharmacological functional groups are covalently bound to biodegradable polymers, thus transforming small-molecule drugs into therapeutic biomaterials. When implanted onto the myocardium, the patch releases NO locally through a stepwise biotransformation, and NO generation is remarkably enhanced in infarcted myocardium because of the ischemic microenvironment, which gives rise to mitochondrial-targeted cardioprotection as well as enhanced cardiac repair. The therapeutic efficacy is further confirmed in a clinically relevant porcine model of myocardial infarction. All these results support the translational potential of this functional patch for treating ischemic heart disease by therapeutic mechanisms different from conventional organic nitrate drugs.


Assuntos
Implantes de Medicamento/metabolismo , Infarto do Miocárdio/metabolismo , Nitratos/metabolismo , Óxidos de Nitrogênio/metabolismo , Animais , Cardiotônicos/metabolismo , Cardiotônicos/farmacologia , Modelos Animais de Doenças , Implantes de Medicamento/farmacologia , Coração/efeitos dos fármacos , Coração/fisiopatologia , Ativação de Macrófagos/efeitos dos fármacos , Masculino , Camundongos , Infarto do Miocárdio/mortalidade , Infarto do Miocárdio/prevenção & controle , Isquemia Miocárdica/metabolismo , Isquemia Miocárdica/prevenção & controle , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Células RAW 264.7 , Ratos Sprague-Dawley , Taxa de Sobrevida , Suínos
16.
Methods Mol Biol ; 2320: 183-192, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34302659

RESUMO

Heart failure is caused by a complicated pathogenic process and has a poor prognosis. Quality of life is often impaired due to repeated hospitalization. Integrative analysis of the morphological, physiological, and molecular profiles of cardiomyocytes, which are responsible mainly for heart contraction, may lead to a deeper understanding of the pathogenesis of heart failure. However, unlike other types of cells, cardiomyocytes are relatively large, vulnerable to stress, and difficult to use for single-cell analysis. With some ingenuity, we have established a single-cardiomyocyte analysis pipeline. Here, we describe the procedure for single-cell RNA sequencing of adult mouse cardiomyocytes from isolation to analysis.


Assuntos
Coração/fisiopatologia , Miocárdio/química , Miócitos Cardíacos/química , RNA-Seq/métodos , Análise de Célula Única/métodos , Animais , Desenho de Equipamento , Biblioteca Gênica , Insuficiência Cardíaca/fisiopatologia , Masculino , Camundongos , Perfusão/instrumentação , Perfusão/métodos , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Manejo de Espécimes
17.
Int J Mol Sci ; 22(14)2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34298968

RESUMO

Mitochondrial dysfunction is considered the major contributor to skeletal muscle wasting in different conditions. Genetically determined neuromuscular disorders occur as a result of mutations in the structural proteins of striated muscle cells and therefore are often combined with cardiac phenotype, which most often manifests as a cardiomyopathy. The specific roles played by mitochondria and mitochondrial energetic metabolism in skeletal muscle under muscle-wasting conditions in cardiomyopathies have not yet been investigated in detail, and this aspect of genetic muscle diseases remains poorly characterized. This review will highlight dysregulation of mitochondrial representation and bioenergetics in specific skeletal muscle disorders caused by mutations that disrupt the structural and functional integrity of muscle cells.


Assuntos
Cardiomiopatias/genética , Coração/fisiopatologia , Mitocôndrias Musculares/metabolismo , Músculo Esquelético/metabolismo , Doenças Neuromusculares/genética , Animais , Cardiomiopatias/metabolismo , Cardiomiopatias/patologia , Modelos Animais de Doenças , Metabolismo Energético , Humanos , Camundongos , Mitocôndrias Cardíacas/metabolismo , Proteínas Musculares/deficiência , Proteínas Musculares/genética , Proteínas Musculares/fisiologia , Músculo Esquelético/ultraestrutura , Atrofia Muscular/metabolismo , Distrofias Musculares/genética , Distrofias Musculares/metabolismo , Distrofias Musculares/patologia , Distrofia Muscular Animal/genética , Distrofia Muscular Animal/metabolismo , Distrofia Muscular Animal/patologia , Doenças Neuromusculares/metabolismo , Doenças Neuromusculares/patologia , Fenótipo
18.
Int Heart J ; 62(4): 792-800, 2021 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-34276003

RESUMO

Myocardial contrast echocardiography (MCE) and two-dimensional speckle tracking echocardiography (2D-STE) were used to detect left ventricular myocardial microcirculation perfusion and myocardial systolic function in dilated cardiomyopathy (DCM) and to explore the relationship between the two.Conventional ultrasound, MCE, and 2D-STE examinations were performed on 30 patients and 30 controls. Left ventricular microcirculation perfusion, left ventricular longitudinal strain (GLS), and circumferential strain (GCS) were analyzed to further compare the correlation between left ventricular perfusion and myocardial strain parameters.Regional myocardial perfusion was reduced in patients with DCM, manifesting as a decrease in the rising slope (A) of the mid-segment of the posterior septum, the peak intensity (PI) of the mid-segment of the anterior septum and the posterior septum, the apical segment of the lateral wall, the area under the curve (AUC) of the posterior septum, the basal segment of the posterior wall, the anterior septum, posterior septum, posterior wall, mid-segment of the lateral wall, and apical segment of the lateral wall and the overall average PI and AUC of the mid-segment, compared with that in the controls (P < 0.05). The left ventricular systolic function and the strain parameters GLS and GCS of DCM patients were lower than those of the controls (P < 0.001). Correlation analysis revealed a positive correlation between the A of the mitral valve and GCS (r = 0.372, P = 0.043), and MV-E/e' had a positive correlation with the AUC of the basal and intermediate segments (r = 0.379, P = 0.039; r = 0.404, P = 0.027).In patients with DCM, regional myocardial microcirculation perfusion is reduced, and myocardial strain is impaired. Myocardial perfusion has a good positive correlation with myocardial mechanics.


Assuntos
Cardiomiopatia Dilatada/fisiopatologia , Ecocardiografia/métodos , Coração/fisiopatologia , Imagem de Perfusão do Miocárdio/métodos , Adulto , Cardiomiopatia Dilatada/diagnóstico por imagem , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
19.
Rev Cardiovasc Med ; 22(2): 365-371, 2021 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-34258904

RESUMO

COVID-19 is a novel viral infection caused by severe acute respiratory syndrome (SARS) beta-coronavirus. Epidemiological status changes dynamically as the pandemy is far from ending. Several complications of presented virus may be similar to those observed in other viral infections. Despite lacking data, the heart involvement may be comparable to cardiac complications observed previously in those with SARS as well as Middle East Respiratory Syndrome (MERS). In COVID-19 we observe elevated levels of cardiac biomarkers, such as natriuretic peptides, troponins, myoglobin, C-reactive protein (CRP), interleukin-2 (IL-2), interleukin-6 (IL-6) and ferritin, which is likely the result of myocardial injury. The possible mechanisms of cardiovascular injury include direct toxicity through the viral invasion of cardiac myocytes, ACE-2 receptor-mediated CV (cardiac and endothelial) injury, microvascular dysfunction and thrombosis and cytokine release syndrome (mainly IL-6 mediated). Cardiac manifestations of COVID-19 are focal or global myocardial inflammation, necrosis, ventricular dysfunction, heart failure and arrhythmia.


Assuntos
COVID-19/virologia , Cardiopatias/virologia , Coração/virologia , SARS-CoV-2/patogenicidade , COVID-19/mortalidade , COVID-19/fisiopatologia , COVID-19/terapia , Coração/fisiopatologia , Cardiopatias/mortalidade , Cardiopatias/fisiopatologia , Cardiopatias/terapia , Interações Hospedeiro-Patógeno , Humanos , Prognóstico , Fatores de Risco , SARS-CoV-2/efeitos dos fármacos
20.
Nutrients ; 13(6)2021 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-34073024

RESUMO

L-carnitine (LC) supplementation improves cardiac function in hemodialysis (HD) patients. However, whether reducing LC supplementation affects carnitine kinetics and cardiac function in HD patients treated with LC remains unclear. Fifty-nine HD patients previously treated with intravenous LC 1000 mg per HD session (three times weekly) were allocated to three groups: LC injection three times weekly, once weekly, and placebo, and prospectively followed up for six months. Carnitine fractions were assessed by enzyme cycling methods. Plasma and red blood cell (RBC) acylcarnitines were profiled using tandem mass spectrometry. Cardiac function was evaluated using echocardiography and plasma B-type natriuretic peptide (BNP) levels. Reducing LC administration to once weekly significantly decreased plasma carnitine fractions and RBC-free carnitine levels during the study period, which were further decreased in the placebo group (p < 0.001). Plasma BNP levels were significantly elevated in the placebo group (p = 0.03). Furthermore, changes in RBC (C16 + C18:1)/C2 acylcarnitine ratio were positively correlated with changes in plasma BNP levels (ß = 0.389, p = 0.005). Reducing LC administration for six months significantly decreased both plasma and RBC carnitine levels, while the full termination of LC increased plasma BNP levels; however, it did not influence cardiac function in HD patients.


Assuntos
Carnitina/sangue , Carnitina/farmacocinética , Suplementos Nutricionais , Insuficiência Cardíaca/prevenção & controle , Coração/efeitos dos fármacos , Falência Renal Crônica/terapia , Diálise Renal/métodos , Idoso , Carnitina/administração & dosagem , Relação Dose-Resposta a Droga , Feminino , Seguimentos , Coração/fisiopatologia , Insuficiência Cardíaca/complicações , Humanos , Falência Renal Crônica/sangue , Falência Renal Crônica/complicações , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Método Simples-Cego
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...