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1.
Am J Cardiol ; 128: 45-53, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32650923

RESUMO

Early-onset cardiomyopathy is a major concern for people with type 1 diabetes mellitus (DM). Studies examining myocardial deformation indices early in the disease process in people with have provided conflicting results. Accordingly, the objective was to examine left ventricular (LV) function in adolescents with type 1 DM using novel measures of cardiomyopathy, termed ventricular discoordination indices, including systolic stretch fraction (SSF), and our newly developed diastolic relaxation fraction (DRF). Adolescents with DM (n = 16) and healthy controls (n = 20) underwent cardiac MRI (CMR) tissue tracking analysis for standard volumetric and functional analysis. Segment-specific circumferential strain and strain rate indices were evaluated to calculate standard mechanical dyssynchrony and discoordination. SSF and DRF were calculated from strain rate data. There were no global or regional group differences between participants with DM and controls in standard LV strain mechanics. However, youth with DM had lower diastolic strain rate around the inferior septal and free wall region (all p <0.05) as well as higher SSF (p = 0.03) and DRF (p <0.001) compared with controls. None of the CMR indices correlated with HbA1c or diabetes duration. In conclusion, our results suggest that adolescents with DM have LV systolic and diastolic discoordination, providing early evidence of cardiomyopathy despite their young age. The presence of discoordination in the setting of normal LV size and function suggests that the proposed novel discoordination indices could serve as a more sensitive marker of cardiomyopathy than previously employed mechanical deformation indices.


Assuntos
Diabetes Mellitus Tipo 1/epidemiologia , Contração Miocárdica/fisiologia , Disfunção Ventricular Esquerda/epidemiologia , Função Ventricular Esquerda , Adolescente , Estudos de Casos e Controles , Cardiomiopatias Diabéticas/diagnóstico por imagem , Cardiomiopatias Diabéticas/epidemiologia , Cardiomiopatias Diabéticas/fisiopatologia , Diástole , Feminino , Humanos , Imagem por Ressonância Magnética , Imagem Cinética por Ressonância Magnética , Masculino , Sístole , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/fisiopatologia , Adulto Jovem
3.
Medicine (Baltimore) ; 99(21): e20349, 2020 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-32481325

RESUMO

AIMS: The purpose of the present trial is to determine whether opening co-existing chronic total occlusions (CTOs) using percutaneous coronary interventions (PCIs) improves cardiac function in patients with multi-vessel disease (MVD). Patients with MVD are defined as having at least one additional major vessel exhibiting no less than 75% stenosis combined with the presence of a CTO artery. METHODS AND RESULTS: Patients will be prospectively recruited who meet the following criteria:Patients presenting with no necrosis of myocardial tissue in the territory of the CTO will be excluded. Recruited patients will be randomized into 2 groups: those undergoing PCI of only the non-CTO artery (non-CTO PCI group), and those undergoing PCI of the non-CTO artery concurrently with the CTO artery (CTO-PCI group). The primary outcome will be the change in cardiac function evaluated via CMR at a 12-month of follow-up appointment, which will be compared to a baseline measurement. Secondary outcomes include occurrence of major cardiac events, CMR-assessed myocardial viability in the CTO-supplied territory, and quality of life assessed by Seattle angina questionnaire, Patient Health Questionnaire 9 and Generalized Anxiety Disorder Scale-7 after 12-month follow-up. CONCLUSION: The SOS-moral trial will provide data necessary to determine whether to open concurrent CTOs among MVD patients with CMR-detected necrotic myocardial tissue.


Assuntos
Oclusão Coronária/cirurgia , Vasos Coronários/diagnóstico por imagem , Contração Miocárdica/fisiologia , Intervenção Coronária Percutânea/métodos , Função Ventricular Esquerda/fisiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença Crônica , Angiografia Coronária , Oclusão Coronária/diagnóstico , Vasos Coronários/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento , Adulto Jovem
4.
Anesth Analg ; 131(2): 527-536, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32371741

RESUMO

BACKGROUND: Catecholamine inotropes are frequently used after cardiopulmonary bypass (CPB) but may have undesirable effects. The aim was to identify whether the routine use of inhaled pulmonary vasodilators might reduce the requirement for inotrope drugs after cardiac surgery. METHODS: Retrospective cohort study of sequential patients undergoing cardiac surgery at the Royal Melbourne Hospital performed by a single surgeon and anesthesia care team, within 14 months before and after routine implementation of inhaled pulmonary vasodilators, August 2017. Milrinone 4 mg and iloprost 20 µg were inhaled using a vibrating mesh nebulizer (Aerogen) before initiation of CPB and at chest closure. Other aspects of clinical management were unaltered over the time period. Two investigators blinded to each other extracted data from electronic and written medical records. The primary outcome was any use of inotropes in the perioperative period; a Fisher exact test was used to analyze any differences between the 2 groups. Demographic data, hemodynamic data, and use of inotropes and vasopressors were collected from induction of anesthesia to 36 hours postoperative in the intensive care unit (ICU). Hospital and ICU length of stay, cost, and complications were collected. RESULTS: Any use of inotropes was significantly lower with inhaled pulmonary dilators (62.5% vs 86.8%, odds ratio [95% confidence interval {CI}], 0.253 (0.083-0.764); P = .011), including intraoperative inotrope use (37.5% vs 86.8%, odds ratio [95% CI], 0.091 (0.03-0.275); P < .001). ICU length of stay was significantly lower with inhaled pulmonary dilators (45 hours, interquartile range [IQR], 27-65 vs 50 hours, IQR, 45-74; P = .026). There were no significant differences among major postoperative complications or costs between groups. CONCLUSIONS: Routine use of inhaled milrinone 4 mg and iloprost 20 µg before and after CPB is associated with reduced postoperative inotrope use.


Assuntos
Procedimentos Cirúrgicos Cardíacos/métodos , Iloprosta/administração & dosagem , Complicações Intraoperatórias/prevenção & controle , Milrinona/administração & dosagem , Contração Miocárdica/efeitos dos fármacos , Vasodilatadores/administração & dosagem , Administração por Inalação , Idoso , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Cardiotônicos/administração & dosagem , Estudos de Coortes , Feminino , Humanos , Cuidados Intraoperatórios/métodos , Complicações Intraoperatórias/diagnóstico , Complicações Intraoperatórias/etiologia , Masculino , Pessoa de Meia-Idade , Contração Miocárdica/fisiologia , Projetos Piloto , Estudos Retrospectivos
6.
Am J Cardiol ; 127: 163-168, 2020 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-32444028

RESUMO

Anthracycline-induced cardiotoxicity can lead to clinical and subclinical heart failure. Decrease of global longitudinal strain is a predictor for heart failure. Early detection of subclinical cardiotoxicity is crucial for timely intervention and prevention of further progression. Cardiac function of 41 survivors of childhood acute lymphoblastic leukemia (ALL) was assessed. Values of cardiac troponin T, N-terminal-pro-brain natriuretic peptide, conventional and myocardial 2D strain echocardiography were measured before (T = 0), during (T = 1, cumulative dose of 120 mg/m2), shortly after (T = 2) and long after anthracycline treatment (T = 3, ≥5 years after anthracycline exposure). Cardiac function of survivors at the latest follow up was compared with 70 healthy age-matched controls. None of the survivors showed clinical signs of cardiac failure at T = 3. Strain values decreased during anthracycline treatment and an ongoing reduction was seen at the latest follow-up (T = 3) with preserved cardiac function (normal ejection fraction and shortening fraction). At T = 1, a relative reduction in longitudinal strain (≥10% compared with baseline) was observed in 38% of the survivors, which increased to 54% at T=3. ALL survivors showed significantly lower conventional and myocardial 2D strain values, especially strain rate, compared with healthy age-matched controls. At T = 3, we did not find any abnormal cardiac troponin T levels. Six percent of the survivors showed abnormal N-terminal-pro-brain natriuretic peptide levels. This prospective study showed an ongoing reduction of 2D myocardial strain and strain rate, with preserved left ventricular ejection fraction (≤10% decrease compared with baseline) in asymptomatic ALL survivors at late follow-up.


Assuntos
Antraciclinas/uso terapêutico , Ecocardiografia/métodos , Eletrocardiografia , Cardiopatias/fisiopatologia , Contração Miocárdica/fisiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Adolescente , Criança , Pré-Escolar , Feminino , Seguimentos , Cardiopatias/diagnóstico , Cardiopatias/etiologia , Humanos , Masculino , Países Baixos/epidemiologia , Projetos Piloto , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida/tendências , Fatores de Tempo
7.
Artigo em Inglês | MEDLINE | ID: mdl-32383992

RESUMO

Engineered heart tissues (EHTs) have emerged as a robust in vitro model to study cardiac physiology. Although biomimetic culture environments have been developed to better approximate in vivo conditions, currently available methods do not permit full recapitulation of the four phases of the cardiac cycle. We have developed a bioreactor which allows EHTs to undergo cyclic loading sequences that mimic in vivo work loops. EHTs cultured under these working conditions exhibited enhanced concentric contractions but similar isometric contractions compared with EHTs cultured isometrically. EHTs that were allowed to shorten cyclically in culture had increased capacity for contractile work when tested acutely. Increased work production was correlated with higher levels of mitochondrial proteins and mitochondrial biogenesis; this effect was eliminated when tissues were cyclically shortened in the presence of a myosin ATPase inhibitor. Leveraging our novel in vitro method to precisely apply mechanical loads in culture, we grew EHTs under two loading regimes prescribing the same work output but with different associated afterloads. These groups showed no difference in mitochondrial protein expression. In loading regimes with the same afterload but different work output, tissues subjected to higher work demand exhibited elevated levels of mitochondrial protein. Our findings suggest that regulation of mitochondrial mass in cultured human EHTs is potently modulated by the mechanical work the tissue is permitted to perform in culture, presumably communicated through ATP demand. Precise application of mechanical loads to engineered heart tissues in culture represents a novel in vitro method for studying physiological and pathological cardiac adaptation.NEW & NOTEWORTHY In this work, we present a novel bioreactor that allows for active length control of engineered heart tissues during extended tissue culture. Specific length transients were designed so that engineered heart tissues generated complete cardiac work loops. Chronic culture with various work loops suggests that mitochondrial mass and biogenesis are directly regulated by work output.


Assuntos
Mitocôndrias Cardíacas/metabolismo , Proteínas Mitocondriais/metabolismo , Contração Miocárdica/fisiologia , Miocárdio/metabolismo , Humanos , Engenharia Tecidual
8.
PLoS One ; 15(3): e0229609, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32126071

RESUMO

This paper proposes a model-based estimation of left ventricular (LV) pressure for the evaluation of constructive and wasted myocardial work of patients with aortic stenosis (AS). A model of the cardiovascular system is proposed, including descriptions of i) cardiac electrical activity, ii) elastance-based cardiac cavities, iii) systemic and pulmonary circulations and iv) heart valves. After a sensitivity analysis of model parameters, an identification strategy was implemented using a Monte-Carlo cross-validation approach. Parameter identification procedure consists in two steps for the estimation of LV pressures: step 1) from invasive, intraventricular measurements and step 2) from non-invasive data. The proposed approach was validated on data obtained from 12 patients with AS. The total relative errors between estimated and measured pressures were on average 11.9% and 12.27% and mean R2 were equal to 0.96 and 0.91, respectively for steps 1 and 2 of parameter identification strategy. Using LV pressures obtained from non-invasive measurements (step 2) and patient-specific simulations, Global Constructive (GCW), Wasted (GWW) myocardial Work and Global Work Efficiency (GWE) parameters were calculated. Correlations between measures and model-based estimations were 0.88, 0.80, 0.91 respectively for GCW, GWW and GWE. The main contributions concern the proposal of the parameter identification procedure, applied on an integrated cardiovascular model, able to reproduce LV pressure specifically to each AS patient, by non-invasive procedures, as well as a new method for the non-invasive estimation of constructive, wasted myocardial work and work efficiency in AS.


Assuntos
Estenose da Valva Aórtica/fisiopatologia , Modelos Cardiovasculares , Pressão Ventricular/fisiologia , Idoso , Idoso de 80 Anos ou mais , Simulação por Computador , Feminino , Humanos , Masculino , Método de Monte Carlo , Contração Miocárdica/fisiologia , Modelagem Computacional Específica para o Paciente , Estudos Prospectivos , Volume Sistólico/fisiologia , Função Ventricular Esquerda/fisiologia
9.
Radiol Med ; 125(5): 444-450, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32125636

RESUMO

OBJECTIVES: Myocardial strains can be calculated using cardiovascular magnetic resonance (CMR) feature-tracking (FT) algorithms. They show excellent intra- and inter-observer agreement but rather disappointing inter-vendor agreement. Currently, it is unknown how well CMR-FT-based strain values agree with manually obtained strain values. METHODS: In 45 subjects (15 controls, 15 acute myocardial infarction, 15 non-ischemic dilated cardiomyopathy), end-systolic manually derived strains were compared to four CMR-FT software packages. Global radial strain (GRS), global circumferential strain (GCS) and global longitudinal strain (GLS) were determined. Intra- and inter-observer agreement and agreement between manual and CMR-FT analysis were calculated. Statistical analysis included Bland-Altman plots, intra-class correlation coefficient (ICC) and coefficient of variation (CV). RESULTS: Manual contouring yielded excellent intra-observer (ICC 0.903 (GRS) to 0.995 (GCS)) and inter-observer agreement (ICC 0.915 (GRS) to 0.966 (GCS)) with CV ranging 4.7% (GCS) to 20.7% (GRS) and 12.7% (GCS) to 20.0% (GRS), for intra-observer and inter-observer agreement, respectively. Agreement between manual and CMR-FT strain values ranged from poor to excellent, with best agreement for GCS (ICC 0.857-0.935) and intermediate for GLS (ICC 0.591-0.914), while ICC values for GRS ranged widely (ICC 0.271-0.851). In particular, two software packages showed a strong trend toward systematic underestimation of myocardial strain in radial and longitudinal direction, correlating poorly to moderately with manual contouring, i.e., GRS (ICC 0.271, CV 25.2%) and GLS (ICC 0.591, CV 17.6%). CONCLUSION: Some CMR-FT values agree poorly with manually derived strains, emphasizing to be cautious to use these software packages in the clinical setting. In particular, radial and longitudinal strain tends to be underestimated when using manually derived strains as reference.


Assuntos
Algoritmos , Cardiomiopatia Dilatada/diagnóstico por imagem , Imagem Cinética por Ressonância Magnética/métodos , Infarto do Miocárdio/diagnóstico por imagem , Software , Estresse Mecânico , Disfunção Ventricular Esquerda/diagnóstico por imagem , Análise de Variância , Fenômenos Biomecânicos/fisiologia , Cardiomiopatia Dilatada/fisiopatologia , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Contração Miocárdica/fisiologia , Infarto do Miocárdio/fisiopatologia , Reprodutibilidade dos Testes , Disfunção Ventricular Esquerda/fisiopatologia , Função Ventricular Esquerda/fisiologia
10.
Proc Natl Acad Sci U S A ; 117(14): 8177-8186, 2020 04 07.
Artigo em Inglês | MEDLINE | ID: mdl-32220962

RESUMO

Myosin-based mechanisms are increasingly recognized as supplementing their better-known actin-based counterparts to control the strength and time course of contraction in both skeletal and heart muscle. Here we use synchrotron small-angle X-ray diffraction to determine the structural dynamics of local domains of the myosin filament during contraction of heart muscle. We show that, although myosin motors throughout the filament contribute to force development, only about 10% of the motors in each filament bear the peak force, and these are confined to the filament domain containing myosin binding protein-C, the "C-zone." Myosin motors in domains further from the filament midpoint are likely to be activated and inactivated first in each contraction. Inactivated myosin motors are folded against the filament core, and a subset of folded motors lie on the helical tracks described previously. These helically ordered motors are also likely to be confined to the C-zone, and the associated motor conformation reforms only slowly during relaxation. Myosin filament stress-sensing determines the strength and time course of contraction in conjunction with actin-based regulation. These results establish the fundamental roles of myosin filament domains and the associated motor conformations in controlling the strength and dynamics of contraction in heart muscle, enabling those structures to be targeted to develop new therapies for heart disease.


Assuntos
Proteínas de Transporte/metabolismo , Contração Miocárdica/fisiologia , Miocárdio/metabolismo , Miosinas/fisiologia , Sarcômeros/metabolismo , Animais , Proteínas de Transporte/ultraestrutura , Masculino , Miosinas/ultraestrutura , Domínios Proteicos/fisiologia , Ratos , Sarcômeros/ultraestrutura , Síncrotrons , Difração de Raios X/instrumentação
11.
PLoS One ; 15(2): e0229519, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32097438

RESUMO

BACKGROUND: Measures of cardiac ventricular electrophysiology have been associated with cognitive performance in cross-sectional studies. We sought to evaluate the association of worsening ventricular repolarization in midlife, as measured by incident prolonged QT interval, with cognitive decline in late life. METHODS: Midlife QT interval was assessed by electrocardiography during three study visits from 1965/68 to 1971/74 in a cohort of Japanese American men aged 46-68 at Exam 1 from the Honolulu Heart Study. We defined incident prolonged QT as the QT interval in the upper quartile at Exam 2 or 3 after QT interval in lower three quartiles at Exam 1. Cognitive performance was assessed at least once using the Cognitive Abilities Screening Instrument (CASI), scored using item response theory (CASI-IRT), during four subsequent visits from 1991/93 to 1999/2000 among 2,511 of the 4,737 men in the Honolulu-Asia Aging Study otherwise eligible for inclusion in analyses. We used marginal structural modeling to determine the association of incident prolonged QT with cognitive decline, using weighting to account for confounding and attrition. RESULTS: Incident prolonged QT interval in midlife was not associated with late-life CASI-IRT at cognitive baseline (estimated difference in CASI-IRT: 0.04; 95% CI: -0.28, 0.35; p = 0.81), or change in CASI-IRT over time (estimated difference in annual change in CASI-IRT: -0.002; 95%CI: -0.013, 0.010; p = 0.79). Findings were consistent across sensitivity analyses. CONCLUSIONS: Although many midlife cardiovascular risk factors and cardiac structure and function measures are associated with late-life cognitive decline, incident prolonged QT interval in midlife was not associated with late-life cognitive performance or cognitive decline.


Assuntos
Cognição/fisiologia , Frequência Cardíaca/fisiologia , Contração Miocárdica/fisiologia , Idoso , Envelhecimento , Americanos Asiáticos , Eletrofisiologia Cardíaca/métodos , Transtornos Cognitivos/fisiopatologia , Disfunção Cognitiva/complicações , Estudos de Coortes , Estudos Transversais , Humanos , Hipertensão/complicações , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Estados Unidos
12.
PLoS One ; 15(2): e0228027, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32101554

RESUMO

BACKGROUND: The slope of the relationship between segmental PreS and total systolic shortening (S) has been proposed as a non-invasive index of left ventricular contractility. The aim of this study was to correlate this novel parameter to invasive gold standard measurements of contractility and to investigate how it is influenced by afterload. METHODS: In domestic pigs, afterload was increased by either balloon inflation in the aorta or by administration of phenylephrine while contractility was increased by dobutamine infusion. During all interventions, left ventricular pressure-volume measurements and trans-diaphragmatic two-dimensional echocardiographic images were acquired. The PreS-S slope was constructed from 18 segmental strain curves obtained by speckle tracking analysis and compared to the slope of the end systolic PV relationship (Emax) and the pre-load recruitable stroke work (PRSW). RESULTS: Sixteen datasets of increased contractility and afterload were analyzed. During dobutamine infusion, the LV volumes decreased (p<0.05) while ejection fraction increased (p<0.05). Emax, PRSW and the slope of the intra-ventricular PreS-S relation increased significantly during dobutamine infusion. Afterload increase led to increase in systolic blood pressure (105±16mmHg vs. 138±25mmHg; p<0.01) and decrease of LV stroke volume and ejection fraction (p<0.01). The PreS-S slope was not influenced by loading conditions in concordance with the PRSW findings. The absolute values of the PreS-S slope did not correlate with Emax or PRSW. However, the change of the PreS-S slope in relation with different interventions demonstrated good correlation with changes in PRSW or Emax, (r = 0.66, p<0.05 and r = 0.69, p<0.05). CONCLUSIONS: The slope of the PreS-S relationship is sensitive to changes in inotropy and is less load-dependent than conventional non-invasive parameters of left ventricular function. The magnitude of the change of this slope correlates well with changes in invasive contractility measurements making it an attractive parameter to assess contractile reserve or contractile changes during longitudinal follow-up of patients.


Assuntos
Ventrículos do Coração/fisiopatologia , Contração Miocárdica/fisiologia , Animais , Pressão Sanguínea , Análise de Dados , Feminino , Hemodinâmica , Masculino , Suínos
13.
Transplantation ; 104(9): 1869-1878, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32058468

RESUMO

BACKGROUND: Triple progressive thermopreconditioning (3PTP) may induce high Hsp-70 expression to maintain cardiac function. We suggest that 3PTP may reduce myocardial ischemia/reperfusion (I/R) injury during organ transplantation through Bag3/Hsp-70 mediated defense mechanisms. METHODS: Male Wistar rats were divided into sham control group and 72 h after 3PTP in a 42°C water bath (3PTP) group. Rats underwent 60 min of ischemia by occlusion of the left anterior descending coronary artery followed by 240 min reperfusion. Hemodynamic parameters, including the electrocardiogram, microcirculation, heart rate, left ventricular end-diastolic pressure, maximal rate of rise (+dp/dt), and fall (-dp/dt) in the left ventricular pressure for index of contraction and relaxation were determined. Myocardial infarct size was evaluated by the Evans blue-2,3,5-triphenyltetrazolium chloride method. 3PTP-induced protective mechanisms were determined by Western blot and immunohistochemistry. RESULTS: Cardiac I/R depressed cardiac microcirculation, induced S-T segment elevation, and R-R and P-R interval elongation increased infarct size associated with erythrocyte extravasation, leukocytes and macrophage/monocyte infiltration, granulocyte colony-stimulating factor, poly(ADP-ribose) polymerase 1 stain, and transferase-mediated dUTP-biotin nick end labeling positive cells. However, 3PTP evoked significant cardioprotection against I/R injury, characterized by the increased +dp/dt value and the decreased elevated left ventricular end-diastolic pressure, erythrocyte extravasation, leukocyte and macrophage/monocyte infiltration, granulocyte colony-stimulating factor expression, poly(ADP-ribose) polymerase 1 expression, transferase-mediated dUTP-biotin nick end labeling positive cells, and fragmentation and infarct area. In addition, 3PTP increased Hsp-70 and Bag3 expression and decreased Bax/Bcl-2 ratio, but did not affect the Beclin-1 and LC3-II/LC3-I ratio in the heart with I/R injury. CONCLUSIONS: 3PTP therapies may through Bag3 upregulation alleviate I/R injury-induced left ventricular structural deterioration and dysfunction.


Assuntos
Ventrículos do Coração/patologia , Precondicionamento Isquêmico Miocárdico , Contração Miocárdica/fisiologia , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Disfunção Ventricular Esquerda/prevenção & controle , Proteínas Adaptadoras de Transdução de Sinal/fisiologia , Animais , Apoptose , Proteínas Reguladoras de Apoptose/fisiologia , Fator Estimulador de Colônias de Granulócitos/farmacologia , Masculino , Microcirculação , Traumatismo por Reperfusão Miocárdica/patologia , Proteínas Proto-Oncogênicas c-bcl-2/análise , Ratos , Ratos Wistar
14.
PLoS One ; 15(1): e0219876, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31905197

RESUMO

Computational models of the cardiovascular system and specifically heart function are currently being investigated as analytic tools to assist medical practice and clinical trials. To achieve clinical utility, models should be able to assimilate the diagnostic multi-modality data available for each patient and generate consistent representations of the underlying cardiovascular physiology. While finite element models of the heart can naturally account for patient-specific anatomies reconstructed from medical images, optimizing the many other parameters driving simulated cardiac functions is challenging due to computational complexity. With the goal of streamlining parameter adaptation, in this paper we present a novel, multifidelity strategy for model order reduction of 3-D finite element models of ventricular mechanics. Our approach is centered around well established findings on the similarity between contraction of an isolated muscle and the whole ventricle. Specifically, we demonstrate that simple linear transformations between sarcomere strain (tension) and ventricular volume (pressure) are sufficient to reproduce global pressure-volume outputs of 3-D finite element models even by a reduced model with just a single myocyte unit. We further develop a procedure for congruency training of a surrogate low-order model from multi-scale finite elements, and we construct an example of parameter optimization based on medical images. We discuss how the presented approach might be employed to process large datasets of medical images as well as databases of echocardiographic reports, paving the way towards application of heart mechanics models in the clinical practice.


Assuntos
Insuficiência Cardíaca/diagnóstico por imagem , Ventrículos do Coração/diagnóstico por imagem , Modelos Cardiovasculares , Contração Miocárdica/fisiologia , Função Ventricular Esquerda/fisiologia , Idoso , Fenômenos Biomecânicos , Simulação por Computador , Ecocardiografia , Feminino , Análise de Elementos Finitos , Insuficiência Cardíaca/fisiopatologia , Ventrículos do Coração/fisiopatologia , Humanos , Masculino , Sarcômeros/fisiologia
15.
J Am Coll Cardiol ; 75(1): 1-13, 2020 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-31918815

RESUMO

BACKGROUND: The presence and significance of neural remodeling in premature ventricular contraction-induced cardiomyopathy (PVC-CM) remain unknown. OBJECTIVES: This study aimed to characterize cardiac sympathovagal balance and proarrhythmia in a canine model of PVC-CM. METHODS: In 12 canines, the investigators implanted epicardial pacemakers and radiotelemetry units to record cardiac rhythm and nerve activity (NA) from the left stellate ganglion (SNA), left cardiac vagus (VNA), and arterial blood pressure. Bigeminal PVCs (200 ms coupling) were applied for 12 weeks to induce PVC-CM in 7 animals then disabled for 4 weeks to allow complete recovery of left ventricular ejection fraction (LVEF), versus 5 sham controls. RESULTS: After 12 weeks of PVCs, LVEF (p = 0.006) and dP/dT (p = 0.007) decreased. Resting SNA (p = 0.002) and VNA (p = 0.04), exercise SNA (p = 0.01), SNA response to evoked PVCs (p = 0.005), heart rate (HR) at rest (p = 0.003), and exercise (p < 0.04) increased, whereas HR variability (HRV) decreased (p = 0.009). There was increased spontaneous atrial (p = 0.02) and ventricular arrhythmias (p = 0.03) in PVC-CM. Increased SNA preceded both atrial (p = 0.0003) and ventricular (p = 0.009) arrhythmia onset. Clonidine suppressed SNA and abolished all arrhythmias. After disabling PVC for 4 weeks, LVEF (p = 0.01), dP/dT (p = 0.047), and resting VNA (p = 0.03) recovered to baseline levels. However, SNA, resting HR, HRV, and atrial (p = 0.03) and ventricular (p = 0.03) proarrhythmia persisted. There was sympathetic hyperinnervation in stellate ganglia (p = 0.02) but not ventricles (p = 0.2) of PVC-CM and recovered animals versus sham controls. CONCLUSIONS: Neural remodeling in PVC-CM is characterized by extracardiac sympathetic hyperinnervation and sympathetic neural hyperactivity that persists despite normalization of LVEF. The altered cardiac sympathovagal balance is an important trigger and substrate for atrial and ventricular proarrhythmia.


Assuntos
Cardiomiopatias/fisiopatologia , Contração Miocárdica/fisiologia , Recuperação de Função Fisiológica/fisiologia , Complexos Ventriculares Prematuros/fisiopatologia , Remodelação Ventricular/fisiologia , Animais , Cardiomiopatias/diagnóstico por imagem , Cães , Ecocardiografia/métodos , Eletrocardiografia/métodos , Frequência Cardíaca/fisiologia , Complexos Ventriculares Prematuros/diagnóstico por imagem
16.
Am J Physiol Heart Circ Physiol ; 318(2): H264-H282, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31834834

RESUMO

The ß1-adrenergic regulation of cardiac myocyte contraction plays an important role in regulating heart function. Activation of this system leads to an increased heart rate and stronger myocyte contraction. However, chronic stimulation of the ß1-adrenergic signaling system can lead to cardiac hypertrophy and heart failure. To understand the mechanisms of action of ß1-adrenoceptors, a mathematical model of cardiac myocyte contraction that includes the ß1-adrenergic system was developed and studied. The model was able to simulate major experimental protocols for measurements of steady-state force-calcium relationships, cross-bridge release rate and force development rate, force-velocity relationship, and force redevelopment rate. It also reproduced quite well frequency and isoproterenol dependencies for intracellular Ca2+ concentration ([Ca2+]i) transients, total contraction force, and sarcomere shortening. The mathematical model suggested the mechanisms of increased contraction force and myocyte shortening on stimulation of ß1-adrenergic receptors is due to phosphorylation of troponin I and myosin-binding protein C and increased [Ca2+]i transient resulting from activation of the ß1-adrenergic signaling system. The model was used to simulate work-loop contractions and estimate the power during the cardiac cycle as well as the effects of 4-aminopyridine and tedisamil on the myocyte contraction. The developed mathematical model can be used further for simulations of contraction of ventricular myocytes from genetically modified mice and myocytes from mice with chronic cardiac diseases.NEW & NOTEWORTHY A new mathematical model of mouse ventricular myocyte contraction that includes the ß1-adrenergic system was developed. The model simulated major experimental protocols for myocyte contraction and predicted the effects of 4-aminopyridine and tedisamil on the myocyte contraction. The model also allowed for simulations of work-loop contractions and estimation of the power during the cardiac cycle.


Assuntos
Ventrículos do Coração , Contração Miocárdica/fisiologia , Miócitos Cardíacos/fisiologia , Receptores Adrenérgicos beta 1/fisiologia , Algoritmos , Animais , Sinalização do Cálcio/efeitos dos fármacos , Sinalização do Cálcio/fisiologia , Cardiotônicos/farmacologia , Proteínas de Transporte/metabolismo , Simulação por Computador , Frequência Cardíaca/fisiologia , Ventrículos do Coração/citologia , Ventrículos do Coração/efeitos dos fármacos , Camundongos , Modelos Teóricos , Contração Miocárdica/efeitos dos fármacos , Miócitos Cardíacos/efeitos dos fármacos , Fosforilação , Bloqueadores dos Canais de Potássio/farmacologia , Receptores Adrenérgicos beta 1/efeitos dos fármacos , Sarcômeros/fisiologia , Troponina I/metabolismo , Troponina I/fisiologia
17.
Int J Artif Organs ; 43(1): 25-36, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31387423

RESUMO

BACKGROUND: Right ventricular stroke work index is a useful but invasively measured parameter that can be used to predict right heart failure following continuous-flow left ventricular assist device implantation. Right ventricular contraction pressure index is a novel parameter that was developed to measure right ventricular stroke work index with echocardiography. We aimed to investigate the clinical usefulness of right ventricular contraction pressure index to predict short-term mortality and right heart failure in patients who underwent continuous-flow left ventricular assist device implantation. METHODS: A total of 49 patients who participated in institutional advanced heart failure registry and underwent continuous-flow left ventricular assist device implantation with a bridge-to-candidacy indication were analyzed retrospectively. Right ventricular contraction pressure index was calculated using offline measurements. Demographic, clinical and outcome data were obtained from the registry data. Patients were grouped according to right ventricular contraction pressure index quartiles. RESULTS: Patients within the lowest right ventricular contraction pressure index quartile had a trend toward higher short-term mortality (46.2%, p = 0.056) and combined short-term mortality and definitive right heart failure (53.8%, p = 0.054) at 15th day postoperatively. Similarly, short-term survival or survival free of definite right heart failure were significantly lower in the lowest right ventricular contraction pressure index quartile (log-rank p = 0.045 and log-rank p = 0.03, respectively). In a proportional hazards model that included echocardiographic parameters, right ventricular contraction pressure index was an independent predictor for short-term mortality (odds ratio: 6.777, 95% confidence interval: 1.118-41.098, p = 0.037), but not for combined short-term mortality and definite right heart failure. No such associations were found for long-term mortality. Right ventricular contraction pressure index had a statistically significant correlation with invasively measured pulmonary capillary wedge pressure, pulmonary vascular resistance, mean pulmonary pressure, and right ventricular stroke work index. CONCLUSION: Right ventricular contraction pressure index was found as a useful parameter for determining short-term postoperative mortality in patients undergoing continuous-flow left ventricular assist device implantation.


Assuntos
Insuficiência Cardíaca/mortalidade , Coração Auxiliar , Contração Miocárdica/fisiologia , Disfunção Ventricular Direita/fisiopatologia , Feminino , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Pressão Propulsora Pulmonar/fisiologia , Sistema de Registros , Estudos Retrospectivos , Volume Sistólico/fisiologia , Fatores de Tempo , Resistência Vascular/fisiologia
18.
Artigo em Inglês | MEDLINE | ID: mdl-31676333

RESUMO

Pythons are important models of studies on postprandial metabolism because their physiological responses are exacerbated when digesting large prey. Prior studies of these animals have shown hypertrophy of the cardiac tissue 2 to 3 days after feeding, coinciding with the peak of the specific dynamic action (SDA), but the consequences of this remodeling in myocardial contractility have not been studied, which is the purpose of this work. Specimens of Python molurus were divided into two groups: a Digesting group (2 days after feeding, at the peak of SDA), and a Fasting group (28 days after feeding). When compared to the Fasting group, the Digesting group showed higher relative ventricular mass and calcium-handling protein expression such as sarcoplasmic reticulum Ca2+-ATPase (SERCA), phospholamban (PLB), and the Na+/Ca2+ exchanger (NCX). Digesting pythons also exhibited significant increases in the cardiac contraction force (Fc), rates of force development and relaxation, and cardiac pumping capacity. Therefore, the higher SERCA, PLB and NCX expression levels increased cytosolic Ca2+ transient amplitude, improving myofilament force. These changes are crucial to maintain cardiac output and a relatively high and continuous blood flow required by metabolic expenditure that occurs in postprandial animals.


Assuntos
Boidae/fisiologia , Proteínas de Ligação ao Cálcio/biossíntese , Comportamento Alimentar/fisiologia , Contração Miocárdica/fisiologia , Miocárdio/metabolismo , Proteínas de Répteis/biossíntese , Animais , Mianmar
19.
Curr Probl Cardiol ; 45(1): 100391, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30318107

RESUMO

The metabolic sources of energy for myocardial contractility include mainly free fatty acids (FFA) for 95%, and in lesser amounts for 5% from glucose and minimal contributions from other substrates such lactate, ketones, and amino acids. However, myocardial efficiency is influenced by metabolic condition, overload, and ischemia. During cardiac stress, cardiomyocytes increase glucose oxidation and reduce FFA oxidation. In patients with ischemic coronary disease and heart failure, the low oxygen availability limits myocardial reliance on FFA and glucose utilization must increase. Although glucose uptake is fundamental to cardiomyocyte function, an excessive intracellular glucose level is detrimental. Insulin plays a fundamental role in maintaining myocardial efficiency and in reducing glycemia and inflammation; this is particularly evident in obese and type-2 diabetic patients. An excess of F availability increase fat deposition within cardiomyocytes and reduces glucose oxidation. In patients with high body mass index, a restricted diet or starvation have positive effects on cardiac metabolism and function while, in patients with low body mass index, restrictive diets, or starvation have a deleterious effect. Thus, weight loss in obese patients has positive impacts on ventricular mass and function, whereas, in underweight heart failure patients, such weight reduction adds to the risk of heart damage, predisposing to cachexia. Nutrition plays an essential role in the evolution of cardiovascular disease and should be taken into account. An energy-restricted diet improves myocardial efficiency but can represent a potential risk of heart damage, particularly in patients affected by cardiovascular disease. Micronutrient integration has a marginal effect on cardiovascular efficiency.


Assuntos
Doenças Cardiovasculares/metabolismo , Metabolismo Energético , Contração Miocárdica/fisiologia , Miocárdio/metabolismo , Estado Nutricional/fisiologia , Apoio Nutricional/métodos , Aminoácidos/metabolismo , Doenças Cardiovasculares/fisiopatologia , Ácidos Graxos não Esterificados/metabolismo , Glucose/metabolismo , Humanos , Oxirredução
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