Cardioprotective effects of the electrolyte solution sterofundin and the possible underlying mechanisms.

Background: Sterofundin (SF) is one of the most widely used electrolyte solutions in almost all areas of medicine, with particular importance in intensive care. It provides powerful correction of acid-base imbalances, ion fluctuations, and impaired energy metabolism, which are the three most important characteristics after myocardial infarction (MI). However, whether and how SF protects the heart from post-MI damage are largely unknown.

Right ventricular volume overload reboots cardiomyocyte proliferation via immune responses.

Background: Right ventricular volume overload (RVVO) is one of the most important hemodynamic characteristics in children with congenital heart disease (CHD) and heart failure, and cardiomyocyte (CM) proliferation is one of the most vital factors for improving cardiac performance. However, whether and how RVVO reboots CM proliferation remains elusive.

Methods And Results: We first created a neonatal RVVO mouse model via abdominal aorta and inferior vena cava-fistula microsurgery at postnatal day 7 (P7), the edge of CM proliferation window.

Engineered model of heart tissue repair for exploring fibrotic processes and therapeutic interventions.

Advancements in human-engineered heart tissue have enhanced the understanding of cardiac cellular alteration. Nevertheless, a human model simulating pathological remodeling following myocardial infarction for therapeutic development remains essential. Here we develop an engineered model of myocardial repair that replicates the phased remodeling process, including hypoxic stress, fibrosis, and electrophysiological dysfunction.

Hemodynamic Melody of Postnatal Cardiac and Pulmonary Development in Children with Congenital Heart Diseases.

Hemodynamics is the eternal theme of the circulatory system. Abnormal hemodynamics and cardiac and pulmonary development intertwine to form the most important features of children with congenital heart diseases (CHDs), thus determining these children's long-term quality of life. Here, we review the varieties of hemodynamic abnormalities that exist in children with CHDs, the recently developed neonatal rodent models of CHDs, and the inspirations these models have brought us in the areas of cardiomyocyte proliferation and maturation, as well as in alveolar development.

Volume overload impedes the maturation of sarcomeres and T-tubules in the right atria: a potential cause of atrial arrhythmia following delayed atrial septal defect closure.

Adult patients with atrial septal defects (ASD), the most common form of adult congenital heart disease, often die of arrhythmias, and the immaturity of cardiomyocytes contributes significantly to arrhythmias. ASD typically induces a left-to-right shunt, which then leads to the right atrium (RA) volume overload (VO). Whether or not VO contributes to RA cardiomyocyte immaturity and thereby causes arrhythmias in adult patients with ASD remains unclear.

A surgical mouse model of neonatal right ventricular outflow tract obstruction by pulmonary artery banding.

Backgroud: Diseased animal models play an extremely important role in preclinical research. Lacking the corresponding animal models, many basic research studies cannot be carried out, and the conclusions obtained are incomplete or even incorrect. Right ventricular (RV) outflow tract (RVOT) obstruction leads to RV pressure overload (PO) and reduced pulmonary blood flow (RPF), which are 2 of the most important pathophysiological characteristics in pediatric cardiovascular diseases and seriously affect the survival rate and long-term quality of life of many children.

Establishment and Confirmation of a Postnatal Right Ventricular Volume Overload Mouse Model.

Right ventricular (RV) volume overload (VO) is common in children with congenital heart disease. In view of distinct developmental stages,the RV myocardium may respond differently to VO in children compared to adults. The present study aims to establish a postnatal RV VO model in mice using a modified abdominal arteriovenous fistula.

A neonatal rat model of pulmonary vein stenosis.

Objectives: Pulmonary vein stenosis (PVS), one of the most challenging clinical problems in congenital heart disease, leads to secondary pulmonary arterial hypertension (PAH) and right ventricular (RV) hypertrophy. Due to the lack of a rodent model, the mechanisms underlying PVS and its associated secondary effects are largely unknown, and treatments are minimally successful. This study developed a neonatal rat PVS model with the aim of increasing our understanding of the mechanisms and developing possible treatments for PVS.

Dynamic changes in P300 enhancers and enhancer-promoter contacts control mouse cardiomyocyte maturation.

Cardiomyocyte differentiation continues throughout murine gestation and into the postnatal period, driven by temporally regulated expression changes in the transcriptome. The mechanisms that regulate these developmental changes remain incompletely defined. Here, we used cardiomyocyte-specific ChIP-seq of the activate enhancer marker P300 to identify 54,920 cardiomyocyte enhancers at seven stages of murine heart development.

Ability of the Right Ventricle to Serve as a Systemic Ventricle in Response to the Volume Overload at the Neonatal Stage.

Background: In children with hypoplastic left heart syndrome (HLHS), volume overload (VO) is inevitable, and the right ventricle (RV) pumps blood into the systemic circulation. Understanding the molecular differences and their different responses to VO between the RV and left ventricle (LV) at the neonatal and highly plastic stages may improve the long-term management of children with HLHS.

Methods And Results: A neonatal rat ventricular VO model was established by the creation of a fistula between the inferior vena cava and the abdominal aorta on postnatal day 1 (P1) and confirmed by echocardiographic and histopathological analyses.

Congenital heart disease-associated pulmonary dysplasia and its underlying mechanisms.

Clinical observation indicates that exercise capacity, an important determinant of survival in patients with congenital heart disease (CHD), is most decreased in children with reduced pulmonary blood flow (RPF). However, the underlying mechanism remains unclear. Here, we obtained human RPF lung samples from children with tetralogy of Fallot as well as piglet and rat RPF lung samples from animals with pulmonary artery banding surgery.

Expression and Predictive Functional Profiles of MicroRNAs Data in Vascularized Composite Allotransplantation Acute Rejection.

Background: This study aimed to investigate the mechanisms of acute rejection for vascularized composite allotransplantation (VCA) using microRNAs (miRNAs) differential expression in a VCA animal model.

Methods: Brown Norway rats were used as transplant donors and Lewis rats as VCA receptors. The changes were divided into different stages before and after transplantation in Lewis rats, and all appearance changes were recorded.

Potential Roles of miRNAs in Acute Rejection for Vascularized Composite Allotransplantation.

Aim: The development of microsurgery has greatly advanced vascularized composite allotransplantation (VCA). However, like organ transplantation, VCA is also limited by acute rejection, and concerns regarding long-term survival and function of the transplanted graft. Therefore, it is necessary to elucidate the molecular mechanisms underlying acute rejection caused by VCA, in order to improve patient survival.

GATA4 Regulates Developing Endocardium Through Interaction With ETS1.

Background: The pioneer transcription factor (TF) GATA4 (GATA Binding Protein 4) is expressed in multiple cardiovascular lineages and is essential for heart development. GATA4 lineage-specific occupancy in the developing heart underlies its lineage specific activities. Here, we characterized GATA4 chromatin occupancy in cardiomyocyte and endocardial lineages, dissected mechanisms that control lineage specific occupancy, and analyzed GATA4 regulation of endocardial gene expression.

Molecular Changes in Prepubertal Left Ventricular Development Under Experimental Volume Overload.

Background: Left ventricular (LV) volume overload (VO), commonly found in patients with chronic aortic regurgitation (AR), leads to a series of left ventricular (LV) pathological responses and eventually irreversible LV dysfunction. Recently, questions about the applicability of the guideline for the optimal timing of valvular surgery to correct chronic AR have been raised in regard to both adult and pediatric patients. Understanding how VO regulates postnatal LV development may shed light on the best timing of surgical or drug intervention.

Volume Overload Initiates an Immune Response in the Right Ventricle at the Neonatal Stage.

Pulmonary regurgitation caused by the correction or palliation of pediatric tetralogy of Fallot (TOF) leads to chronic right ventricular (RV) volume overload (VO), which induces adolescent RV dysfunction. A better understanding of the molecular mechanism by which VO initiates neonatal RV remodeling may bring new insights into the post-surgical management of pediatric TOF. We created a fistula between the abdominal aorta and inferior vena cava on postnatal day 1 (P1) using a rat model to induce neonatal VO.

Postnatal Right Ventricular Developmental Track Changed by Volume Overload.

Background Current right ventricular (RV) volume overload (VO) is established in adult mice. There are no neonatal mouse VO models and how VO affects postnatal RV development is largely unknown. Methods and Results Neonatal VO was induced by the fistula between abdominal aorta and inferior vena cava on postnatal day 7 and confirmed by abdominal ultrasound, echocardiography, and hematoxylin and eosin staining.

Downregulated developmental processes in the postnatal right ventricle under the influence of a volume overload.

The molecular atlas of postnatal mouse ventricular development has been made available and cardiac regeneration is documented to be a downregulated process. The right ventricle (RV) differs from the left ventricle. How volume overload (VO), a common pathologic state in children with congenital heart disease, affects the downregulated processes of the RV is currently unclear.

Dexmedetomidine Protects Human Cardiomyocytes Against Ischemia-Reperfusion Injury Through α2-Adrenergic Receptor/AMPK-Dependent Autophagy.

Ischemia-reperfusion injury (I/R) strongly affects the prognosis of children with complicated congenital heart diseases (CHDs) who undergo long-term cardiac surgical processes. Recently, the α2-adrenergic receptor agonist (Dex) has been reported to protect cardiomyocytes (CMs) from I/R in cellular models and adult rodent models. However, whether and how Dex may protect human CMs in young children remains largely unknown.

Role of Blood Oxygen Saturation During Post-Natal Human Cardiomyocyte Cell Cycle Activities.

Blood oxygen saturation (SaO) is one of the most important environmental factors in clinical heart protection. This study used human heart samples and human induced pluripotent stem cell-cardiomyocytes (iPSC-CMs) to assess how SaO affects human CM cell cycle activities. The results showed that there were significantly more cell cycle markers in the moderate hypoxia group (SaO: 75% to 85%) than in the other 2 groups (SaO <75% or >85%).