RESUMO
Although the rate of preterm birth has increased in recent decades, a number of preterm infants have escaped death due to improvements in perinatal and neonatal care. Antenatal glucocorticoid (GC) therapy has significantly contributed to progression in lung maturation; however, its potential effects on other organs remain controversial. Furthermore, the effects of antenatal GC therapy on the fetal heart show both pros and cons. Translational research in animal models indicates that constant fetal exposure to antenatal GC administration is sufficient for lung maturation. We have established a premature fetal rat model to investigate immature cardiopulmonary functions in the lungs and heart, including the effects of antenatal GC administration. In this review, we explain the mechanisms of antenatal GC actions on the heart in the fetus compared to those in the neonate. Antenatal GCs may contribute to premature heart maturation by accelerating cardiomyocyte proliferation, angiogenesis, energy production, and sarcoplasmic reticulum function. Additionally, this review specifically focuses on fetal heart growth with antenatal GC administration in experimental animal models. Moreover, knowledge regarding antenatal GC administration in experimental animal models can be coupled with that from developmental biology, with the potential for the generation of functional cells and tissues that could be used for regenerative medical purposes in the future.
Assuntos
Glucocorticoides , Nascimento Prematuro , Animais , Metabolismo Energético , Feminino , Coração Fetal , Glucocorticoides/farmacologia , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Gravidez , RatosAssuntos
Vacinas contra COVID-19 , COVID-19 , Miocardite , Doença Aguda , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Meios de Contraste/efeitos adversos , Gadolínio , Humanos , Imageamento por Ressonância Magnética/métodos , Imagem Cinética por Ressonância Magnética/métodos , Miocardite/diagnóstico por imagem , Miocardite/etiologiaAssuntos
Aneurisma Coronário , Trombose Coronária , Síndrome de Linfonodos Mucocutâneos , Trombose , Aneurisma Coronário/diagnóstico por imagem , Aneurisma Coronário/etiologia , Angiografia Coronária , Trombose Coronária/diagnóstico por imagem , Trombose Coronária/etiologia , Humanos , Síndrome de Linfonodos Mucocutâneos/complicações , Síndrome de Linfonodos Mucocutâneos/diagnóstico , Trombose/diagnóstico por imagem , Trombose/etiologiaRESUMO
We describe a female infant with incontinentia pigmenti complicated by severe pulmonary arterial hypertension that was markedly improved by tadalafil administration. The infant was referred to our institution because of neonatal seizures and generalized skin rash at the age of 1 day. She was diagnosed with incontinentia pigmenti on skin biopsy findings. In addition to incontinentia pigmenti, she had pulmonary arterial hypertension without structural heart disease. The pulmonary hypertension rapidly worsened at the age of 2 months and was confirmed by cardiac catheterization. The pulmonary artery pressure was equal to systemic pressure but it decreased in response to nitric oxide inhalation. We, therefore, initiated treatment with tadalafil of 1â¯mg/kg/day. The follow-up cardiac catheterization performed at 9 months revealed dramatic improvement in the pulmonary artery pressure. An IKBKG mutation with deletion of exons 4-10 was detected in the blood of both the patient and her mother. Our experience indicates that tadalafil may be beneficial in treating pulmonary arterial hypertension associated with incontinentia pigmenti.
Assuntos
Hipertensão Pulmonar/tratamento farmacológico , Incontinência Pigmentar/complicações , Tadalafila/uso terapêutico , Éxons , Feminino , Humanos , Hipertensão Pulmonar/complicações , Hipertensão Pulmonar/diagnóstico por imagem , Hipertensão Pulmonar/fisiopatologia , Quinase I-kappa B/sangue , Quinase I-kappa B/genética , Incontinência Pigmentar/diagnóstico , Recém-Nascido , NF-kappa B/genética , NF-kappa B/metabolismo , Convulsões/genética , Deleção de Sequência , Pele/patologia , Tadalafila/administração & dosagemRESUMO
BACKGROUND: ATP synthesis and cardiac contraction-related protein production are accelerated in the immature fetal heart by antenatal glucocorticoids (GC). This study investigated the structural maturity of the myocardium and underlying signal pathway associated with cardiac growth in fetal rats that received antenatal GC. METHODS AND RESULTS: Dexamethasone (DEX) was given to pregnant rats for 2 days from day 17 or day 19 of gestation, and the hearts of 19 and 21 day fetuses and 1-day-old neonates were analyzed. Although irregular myofibril orientation was observed morphologically in 19 day fetal hearts, the myofibril components were organized in fetuses after DEX. The cross-sectional area of the myocardium and Ki-67-positive cells were significantly increased in fetal DEX groups, suggesting that cardiac enlargement resulted from myocyte proliferation. Glycogen synthase kinase-3ß (GSK-3ß) protein was significantly decreased in fetal DEX groups. ß-Catenin and vascular endothelial growth factor protein were also significantly increased. Furthermore, increased cardiomyocyte proliferation appeared to be mediated by GC receptors after culture with DEX in vitro. CONCLUSIONS: Antenatal DEX induces structural maturity accompanying cardiomyocyte proliferation in the premature fetal rat heart, and GSK-3ß and ß-catenin are thought to contribute to cardiac growth.
Assuntos
Proliferação de Células/efeitos dos fármacos , Dexametasona/farmacologia , Glucocorticoides/farmacologia , Coração/efeitos dos fármacos , Animais , Western Blotting , Células Cultivadas , Feminino , Glicogênio Sintase Quinase 3 beta/metabolismo , Coração/crescimento & desenvolvimento , Imuno-Histoquímica , Antígeno Ki-67/metabolismo , Gravidez , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Ratos , Transdução de Sinais , beta Catenina/metabolismoRESUMO
Importance: Few studies with sufficient statistical power have shown the association of the z score of the coronary arterial internal diameter with coronary events (CE) in patients with Kawasaki disease (KD) with coronary artery aneurysms (CAA). Objective: To clarify the association of the z score with time-dependent CE occurrence in patients with KD with CAA. Design, Setting, and Participants: This multicenter, collaborative retrospective cohort study of 44 participating institutions included 1006 patients with KD younger than 19 years who received a coronary angiography between 1992 and 2011. Main Outcomes and Measures: The time-dependent occurrence of CE, including thrombosis, stenosis, obstruction, acute ischemic events, and coronary interventions, was analyzed for small (z score, <5), medium (z score, ≥5 to <10; actual internal diameter, <8 mm), and large (z score, ≥10 or ≥8 mm) CAA by the Kaplan-Meier method. The Cox proportional hazard regression model was used to identify risk factors for CE after adjusting for age, sex, size, morphology, number of CAA, resistance to initial intravenous immunoglobulin (IVIG) therapy, and antithrombotic medications. Results: Of 1006 patients, 714 (71%) were male, 341 (34%) received a diagnosis before age 1 year, 501 (50%) received a diagnosis between age 1 and 5 years, and 157 (16%) received a diagnosis at age 5 years or older. The 10-year event-free survival rate for CE was 100%, 94%, and 52% in men (P < .001) and 100%, 100%, and 75% in women (P < .001) for small, medium, and large CAA, respectively. The CE-free rate was 100%, 96%, and 79% in patients who were not resistant to IVIG therapy (P < .001) and 100%, 96%, and 51% in patients who were resistant to IVIG therapy (P < .001), respectively. Cox regression analysis revealed that large CAA (hazard ratio, 8.9; 95% CI, 5.1-15.4), male sex (hazard ratio, 2.8; 95% CI, 1.7-4.8), and resistance to IVIG therapy (hazard ratio, 2.2; 95% CI, 1.4-3.6) were significantly associated with CE. Conclusions and Relevance: Classification using the internal diameter z score is useful for assessing the severity of CAA in relation to the time-dependent occurrence of CE and associated factors in patients with KD. Careful management of CE is necessary for all patients with KD with CAA, especially men and IVIG-resistant patients with a large CAA.
Assuntos
Aneurisma Coronário/etiologia , Síndrome de Linfonodos Mucocutâneos/complicações , Adolescente , Criança , Pré-Escolar , Aneurisma Coronário/diagnóstico por imagem , Aneurisma Coronário/epidemiologia , Aneurisma Coronário/patologia , Angiografia Coronária , Doença das Coronárias/diagnóstico por imagem , Doença das Coronárias/epidemiologia , Doença das Coronárias/etiologia , Resistência a Medicamentos , Feminino , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Lactente , Japão/epidemiologia , Estimativa de Kaplan-Meier , Masculino , Síndrome de Linfonodos Mucocutâneos/tratamento farmacológico , Síndrome de Linfonodos Mucocutâneos/epidemiologia , Estudos Retrospectivos , Medição de Risco/métodos , Fatores de Risco , Índice de Gravidade de Doença , Fatores SexuaisRESUMO
BACKGROUND: Several coronary artery Z score models have been developed. However, a Z score model derived by the lambda-mu-sigma (LMS) method has not been established. METHODS: Echocardiographic measurements of the proximal right coronary artery, left main coronary artery, proximal left anterior descending coronary artery, and proximal left circumflex artery were prospectively collected in 3,851 healthy children ≤18 years of age and divided into developmental and validation data sets. In the developmental data set, smooth curves were fitted for each coronary artery using linear, logarithmic, square-root, and LMS methods for both sexes. The relative goodness of fit of these models was compared using the Bayesian information criterion. The best-fitting model was tested for reproducibility using the validation data set. The goodness of fit of the selected model was visually compared with that of the previously reported regression models using a Q-Q plot. RESULTS: Because the internal diameter of each coronary artery was not similar between sexes, sex-specific Z score models were developed. The LMS model with body surface area as the independent variable showed the best goodness of fit; therefore, the internal diameter of each coronary artery was transformed into a sex-specific Z score on the basis of body surface area using the LMS method. In the validation data set, a Q-Q plot of each model indicated that the distribution of Z scores in the LMS models was closer to the normal distribution compared with previously reported regression models. Finally, the final models for each coronary artery in both sexes were developed using the developmental and validation data sets. A Microsoft Excel-based Z score calculator was also created, which is freely available online (http://raise.umin.jp/zsp/calculator/). CONCLUSIONS: Novel LMS models with which to estimate the sex-specific Z score of each internal coronary artery diameter were generated and validated using a large pediatric population.
Assuntos
Vasos Coronários/anatomia & histologia , Vasos Coronários/diagnóstico por imagem , Ecocardiografia/normas , Imageamento Tridimensional/normas , Modelos Estatísticos , Adolescente , Envelhecimento/patologia , Envelhecimento/fisiologia , Algoritmos , Criança , Pré-Escolar , Simulação por Computador , Ecocardiografia/métodos , Feminino , Humanos , Imageamento Tridimensional/métodos , Lactente , Recém-Nascido , Japão/epidemiologia , Masculino , Modelos Cardiovasculares , Pediatria/normas , Valores de Referência , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Caracteres SexuaisRESUMO
BACKGROUND: Platelet aggregation is generally measured by the optical density method. This method is not very sensitive in detecting platelet activation because of the poor correlation between the formation of platelet aggregates and light transmission, and inability to detect small platelet aggregates. Recently, a new method was developed that detects small platelet aggregates formed in the early phase of platelet aggregation by means of a particle counting technique using light scattering. METHODS: The present study used the particle counting method to measure spontaneous platelet aggregation (SPA) produced by agitation with a stirrer bar without agonists in patients with Kawasaki disease (KD) and children's thrombotic disease, and compared the results with the conventional optical density method. RESULTS: Using the particle counting method, significantly higher SPA rates were found before treatment than in healthy adults and at the other stages of treatment. A similar tendency was noted with the optical density method; however, the positive rate of SPA was significantly higher with the particle counting method in each stage except the second stage, which was the period from the start of gamma-globulin therapy to 20 days. CONCLUSION: These results indicate that enhanced platelet aggregation is noted at a high frequency before treatment of KD and that the particle counting method is superior to the optical density method in detecting enhanced platelet aggregation.