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Background: Left ventricular noncompaction (LVNC) is a hereditary type of cardiomyopathy characterized by prominent trabeculations. Detailed characteristics of biventricular noncompaction (BiVNC) remain unknown. This study aimed to elucidate the clinical characteristics and genetic landscape of BiVNC., Methods and Results: We recruited children with left ventricular noncompaction from Japanese multi-institutional centers from 2013 to 2021. Left ventricular noncompaction was classified as BiVNC, congenital heart disease, arrhythmia, dilated cardiomyopathy, or normal function. In these patients, cardiomyopathy-associated genes were screened. A total of 234 patients (127 male; mean age, 4 months [range, 0-6.6 years]) were enrolled in this study, of whom 25 had BiVNC; 55, normal function; 84, dilated cardiomyopathy; 38, congenital heart disease; and 32, arrhythmia. BiVNC was diagnosed during the perinatal period in 10 patients, in whom the prevalence was higher than that in other patients. A total of 14 patients in the group with BiVNC had congenital heart disease, but not necessarily right heart lesions. Left ventricular dyskinesis was frequently observed in the lateral wall (24%) and apex (28%). Eleven pathogenic variants were found in 11 patients with BiVNC (44.0%). The group with BiVNC had a higher ratio of mitochondrial and developmental gene variants than the other groups. Among all groups, the group with BiVNC had the worst survival rate ( P =0.0009)., Conclusions: Pediatric patients with BiVNC had a high rate of ventricular dyskinesis and poor outcome. A comprehensive and careful screening for disease-causing genes and phenotype may help identify specific patients with left ventricular noncompaction and mortality-related cardiac phenotypes.

Background: Cardiac calmodulinopathy, characterized by a life-threatening arrhythmia and sudden death in the young, is extremely rare and caused by genes encoding calmodulin, namely calmodulin 1 (CALM1), CALM2, and CALM3., Methods and results: We screened 195 symptomatic children (age 0-12 years) who were suspected of inherited arrhythmias for 48 candidate genes, using a next-generation sequencer. Ten probands were identified as carrying variants in any of CALM1-3 (5%; median age 5 years), who were initially diagnosed with long QT syndrome (LQTS; n=5), catecholaminergic polymorphic ventricular tachycardia (CPVT; n=3), and overlap syndrome (n=2). Two probands harbored a CALM1 variant and 8 probands harbored 6 CALM2 variants. There were 4 clinical phenotypes: (1) documented lethal arrhythmic events (LAEs): 4 carriers of N98S in CALM1 or CALM2; (2) suspected LAEs: CALM2 p.D96G and D132G carriers experienced syncope and transient cardiopulmonary arrest under emotional stimulation; (3) critical cardiac complication: CALM2 p.D96V and p.E141K carriers showed severe cardiac dysfunction with QTc prolongation; and (4) neurological and developmental disorders: 2 carriers of CALM2 p.E46K showed cardiac phenotypes of CPVT. Beta-blocker therapy was effective in all cases except cardiac dysfunction, especially in combination with flecainide (CPVT-like phenotype) and mexiletine (LQTS-like)., Conclusions: Calmodulinopathy patients presented severe cardiac features, and their onset of LAEs was earlier in life, requiring diagnosis and treatment at the earliest age possible.

Background: Breast milk, nature's optimum source of nutrition for infants, can contain undesirable microorganisms that cause severe morbidity. After an outbreak of multidrug-resistant Escherichia coli among neonates receiving breast milk donated by another mother in our neonatal intensive care unit (NICU), we were motivated to develop a high-grade breast milk pasteurizer (BMP) designed to thaw and pasteurize breast milk at 63°C for 30 min in a sealed bag without having to open the bag or immerse it in water., Methods: Pre-existing bacteria and spiked cytomegalovirus (CMV) were measured pre- and post-pasteurization in frozen breast milk donated by mothers of children admitted to the NICU., Results: Among 48 breast milk samples (mean ± standard deviation [SD]), pre-existing bacterial counts of 5.1±1.1 × 10 4 colony forming units (cfu)/mL decreased to less than 10 cfu/mL (below detection level) in 45 samples after pasteurization for 30 min. In three samples, 10-110 cfu/mL persisted. As no CMV was detected in any of the 48 samples, CMV at ≥5 × 10 4 pfu/mL was spiked into 11 breast milk samples. After just 10 min of pasteurization, infectious CMV was not detected (threshold <50 pfu/mL) in any sample., Conclusion: A new BMP was shown to pasteurize milk effectively with more than a 3-log reduction of microorganisms. Compared to conventional pasteurizers, this device reduces the effort involved in pasteurizing breast milk, avoids various contamination risks, and may reduce the risk of infectious disease transmission via breast milk., (© 2023 The Authors. Pediatrics International published by John Wiley & Sons Australia, Ltd on behalf of Japan Pediatric Society.)

Background: While breastfeeding provides benefits for infants and the mother, many women either do not breastfeed or terminate breastfeeding earlier than recommended. The aim of this analysis was to identify factors associated with early discontinuation of breastfeeding in Japanese women., Methods: This study used data from medical records of women delivering a singleton live birth between March 2017 and August 2019 in Iwase General Hospital, Fukushima Prefecture, Japan to assess cessation of breastfeeding by the 1-month postpartum appointment. Demographic (age at birth, and employment status), medical (parity, and physical and mental condition of the mother; and infant medical factors, such as sex, Apgar score, and jaundice, among other), and family factors (husband/partner, family members living at the same house, among others) in 734 women who had initiated breastfeeding during their delivery hospital stay were examined, and multiple logistic regression was used to determine significant predictors of early cessation of exclusive breastfeeding., Results: Bivariate analysis revealed that women who were primipara, unmarried, exposed to secondhand smoke, and employed; those who smoked before pregnancy; and those who had asthma were more likely to discontinue exclusive breastfeeding than other women. Infant factors associated with discontinuation were lower birthweight, earlier gestational age, neonatal intensive care unit admission, treatment for jaundice, or lower weight gain. Multivariable analysis revealed that primiparity, passive smoking before pregnancy, maternal employment, and neonatal jaundice therapy were associated with discontinuation of breastfeeding., Conclusions: In particular, women whose partners smoked before pregnancy may need to be targeted for additional support for breastfeeding., (© 2022. The Author(s).)

Background: Left ventricular noncompaction (LVNC) is a hereditary cardiomyopathy, associated with high morbidity and mortality, but the role of genetics in cases of fetal-onset has not been fully evaluated. The goal of this study was to identify the genetic background in LVNC fetal-onset patients using next-generation sequencing (NGS)., Methods: Thirty-three fetal-onset Japanese probands with LVNC (20 males and 13 females) were enrolled. In the enrolled patients, 81 genes associated with cardiomyopathy were screened using next-generation sequencing (NGS) retrospectively., Results: Twenty-three patients had congestive heart failure (CHF), and six patients had arrhythmias. Prominent trabeculations were mostly observed in lateral LV, posterior LV, and apex of LV in patients with LVNC. Twelve died; three patients experienced intrauterine death or termination of pregnancy. Overall, 15 variants were found among eight genes in 16 patients. Seven variants were detected in MYH7 and two in TPM1. Sarcomere gene variants accounted for 75.0%. A multivariable proportional hazards model revealed that CHF at diagnosis and a higher ratio of the noncompacted layer/compacted layer in the LV posterior wall were independent risk factors for death in LVNC fetal-onset patients (odds ratio = 4.26 × 10 6 and 1.36 × 10 8 , p = 0.0075 and 0.0005, respectively)., Conclusions: The present study is the first report focusing on genetic background combined with clinical features in LVNC fetal-onset patients using NGS. Sarcomere variants were most commonly identified in fetal-onset patients, and greater attention should be paid to fetal-onset patients with LVNC having prominent trabeculations in the LV because they are more likely to develop CHF., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The pathogenesis of virus-associated acute encephalopathy (VAE) involves brain edema caused by disruption of the blood-brain barrier (BBB). We aimed to develop an in vitro VAE model using an in vitro BBB model, to evaluate the dynamics of vascular dysfunction caused by tumor necrosis factor (TNF)-α. A co-culture model, consisting of Transwell®-grown human brain microvascular endothelial cells and pericytes, was treated with serially diluted TNF-α. Transendothelial electrical resistance (TER) was measured using cellZscope®. A permeability assay, using fluorescein isothiocyanate-conjugated sodium or dextran, was performed. Changes in claudin-5 localization and expression after TNF-α treatment were observed using immunofluorescence staining and western blot analysis. The TER decreased and permeability increased after TNF-α treatment; recovery time was dependent on TNF-α concentration. Claudin-5 was delocalized after TNF-α treatment and recovered in a TNF-α concentration-dependent manner. The expression of claudin-5 decreased 24 h after the TNF-α treatment and completely recovered 48 h after TNF-α treatment. Claudin-5 delocalization was likely associated with vascular hyperpermeability. To conclude, we evaluated vascular endothelial cell permeability and injury in VAE using an in vitro BBB model treated with TNF-α. This system can be useful for developing novel therapeutic strategies for VAE and designing treatments that target vascular permeability.

Platelets parameters including platelet count (PLT), plateletcrit (PCT), mean platelet volume (MPV) and platelet distribution width (PDW) are associated with various physiological and pathological functions in various disease. However, few studies have addressed whether perinatal factors may be associated with platelet parameters at birth in a large cohort of late preterm and term neonates. The aim of this study to investigate perinatal factors affecting platelet parameters in late preterm and term neonates. We retrospectively investigated platelet parameters including PLT, PCT, MPV, and PDW on the first day of life in 142 late preterm and 258 term neonates admitted to our NICU from 2006 through 2020. PLT, MPV, PCT, PDW on Day 0 did not significantly differ between the two groups. In term neonates, multivariate analysis revealed that PCT correlated with being small for gestational age (SGA) (β = -0.168, P = 0.006), pregnancy induced hypertension (PIH) (β = -0.135, P = 0.026) and male sex (β = -0.185, P = 0.002). PLT was associated with SGA (β = -0.186, P = 0.002), PIH (β = -0.137, P = 0.024) and male sex (β = -0.166, P = 0.006). In late preterm neonates, multivariate analysis revealed that PLT were associated with PIH, whereas no factors associated with PDW and MPV were found. In all patients studied, chorioamnionitis (CAM) was significantly associated with MPV (CAM = 10.3 fL vs. no CAM = 9.7 fL, P<0.001). Multivariate analysis showed that SGA, male sex and PIH were associated with PCT and PLT. This study demonstrates that different maternal and neonatal complications affect platelet parameters in late preterm and term neonates., Competing Interests: The authors have declared that no competing interests exist.

Background: During storage, the potassium level of red blood cell (RBC) components increases, especially after irradiation. Neonates are prone to hyperkalemia, for example, non-oliguric hyperkalemia, so using potassium adsorption filters during transfusion may be helpful. To overcome dilution of RBC components caused by saline priming of existing potassium adsorption filters, a downsized potassium adsorption filter for neonates (PAF-n, Kawasumi Laboratories Inc., Tokyo, Japan) was developed., Study Design and Methods: To assess the performance of PAF-n, its adsorption efficiency and RBC recovery rate were evaluated by testing pre-filtration and serial post-filtration (0-30 mL, 30-60 mL, 60-90 mL, and 90-120 mL) samples from 8 RBC components., Results: The average potassium adsorption rate of the PAF-n was 90.5% ± 0.78%, and never less than 89.0% in any of 8 RBC components. RBC recovery rates were 99.3% ± 1.12%., Conclusion: The PAF-n showed an effective potassium ability with negligible RBC dilution., (© 2020 AABB.)

Aim: Effects of nicotine on fetal hemodynamics are not well known, especially in the first trimester fetus. We investigated the acute and chronic effects of nicotine on hemodynamics in pregnant mice and their fetuses using ultrasound. Postnatal health status including growth and hemodynamics was also examined., Methods: To investigate the acute effects of nicotine on fetal hemodynamics, we injected nicotine 0.2 mg/kg subcutaneously into pregnant mice on gestational days (GD) 9.5, 11.5 and 13.5 and compared with saline-injected group. To determine the chronic effects of nicotine on fetal hemodynamics, we administered nicotine in drinking water (0.1 mg/mL) to pregnant mice from GD 6.5 until they gave birth and compared hemodynamics with water-administered mice., Results: Regarding the acute effects of nicotine, we found no intergroup difference in maternal hemodynamics; however, fetal blood flow through the dorsal aorta, carotid artery and umbilical artery tended to decrease, particularly on GD 11.5. Regarding the chronic effects of nicotine, we observed no intergroup difference in maternal body weight changes and hemodynamics; however, blood flow to all fetal organs tended to be lower in the nicotine water group than in the water group with significant difference on GD 13.5. The offspring of the nicotine water group had significantly low birth weights and continued to have low body weight until 9 weeks of age. In addition, these offspring developed postnatal cardiac hypertrophy., Conclusion: Nicotine adversely affects fetal hemodynamics acutely and chronically in early pregnancy, potentially leading to fetal tissue hypoxia, intrauterine growth restriction and adverse postnatal health effects., (© 2020 Japan Society of Obstetrics and Gynecology.)

At 32 weeks of gestation, a male fetus with congenitally corrected transposition of the great arteries developed hydrops fetalis caused by a combination of mitral valve regurgitation and tricuspid valve regurgitation (TR). We performed a pulmonary artery banding (PAB) at 108 days old for gradually progressing TR, after confirming that a balloon dilatation test in the main pulmonary artery reduced TR. As the patient grew, the PAB became tighter and systolic blood pressure in the morphological left ventricle increased. At present, the patient is waiting for a double switch operation.

Premature infants are often exposed to positive pressure ventilation and supplemental oxygen, which leads to the development of chronic lung disease (CLD). There are currently no standard serum biomarkers used for prediction or early detection of patients who go on to develop CLD. MicroRNAs (miRNAs) are a novel class of naturally occurring, short, noncoding substances that regulate gene expression at the posttranscriptional level and cause translational inhibition and/or mRNA degradation and present in body fluids packaged in extracellular vesicles (EVs), rendering them remarkably stable. Our aim was to evaluate miRNAs identified in serum EVs of premature infants as potential biomarkers for CLD. Serum EVs were extracted from premature infants at birth and on the 28th day of life (DOL). Using a human miRNA array, we identified 62 miRNAs that were universally expressed in CLD patients and non-CLD patients. Of the 62 miRNAs, 59 miRNAs and 44 miRNAs were differentially expressed on DOL0 and DOL28 in CLD and non-CLD patients, respectively. Of these miRNAs, serum EV miR-21 was upregulated in CLD patients on DOL28 compared with levels at birth and downregulated in non-CLD patients on DOL28 compared with levels at birth. In neonatal mice exposed to hyperoxia for 7days, as a model of CLD, five miRNAs (miR-34a, miR-21, miR-712, miR-682, and miR-221) were upregulated, and 7 miRNAs (miR-542-5p, miR-449a, miR-322, miR-190b, miR-153, miR-335-3p, miR-377) were downregulated. MiR-21 was detected as a common miRNA that changed in CLD patients and in the hyperoxia exposed mice. We conclude that EV miR-21 may be a biomarker of CLD.

Background: Platelets participate in many physiological and pathological functions and some platelet parameters predict adult diseases. However, few studies report whether platelet parameters may reflect neonatal disease and mortality in a large cohort. Objective: We aimed to investigate whether platelet parameters could predict bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), intraventricular hemorrhage (IVH), and NICU mortality. Study Design and Methods: This retrospective cohort study examined records from 2006 to 2017 at the neonatal intensive care unit (NICU) of Fukushima Medical University Hospital. We retrospectively investigated platelet count, plateletcrit (PCT), mean platelet volume (MPV), and platelet distribution width (PDW) on the first day of life in preterm newborns born <32 weeks' gestation admitted to our NICU from 2006 to 2017. Receiver operating characteristic (ROC) and multiple regression analyses, along with Cox proportional hazard modeling, identified independent predictors of morbidities and mortality in preterm newborns. Results: Of 1,501 neonates admitted to our NICU, a total of 305 preterm newborns were included in this study. Gestational age, birth weight, and Apgar score were significantly lower in non-survivors than in survivors. Platelet count, PCT, PDW and PMI did not differ significantly between the two groups, whereas mean MPV in non-survivors was significantly higher than in survivors (10.5 fl vs. 10.0 fl, p = 0.001). Multivariate Cox hazard modeling showed that shorter GA [HR: 0.628, 95% CI: 0.464-0.840, p = 0.003], male sex [HR: 0.269, 95% CI: 0.113-0.640, p = 0.001], and MPV [HR: 1.469, 95% CI: 1.046-2.063, p = 0.026] independently predicted overall survival. Per receiver operating curve, an MPV threshold of 10.2 fl. MPV predicts prognosis in neonates with a sensitivity of 72.4% and a specificity of 58.6% (AUC = 0.685, 95% CI: 0.600-0.789, p = 0.001). Furthermore, multivariate analysis revealed that platelet parameters were not associated with BPD and NEC, whereas small for gestational age (SGA), Apgar score at 5 min, and low PCT were associated with intraventricular hemorrhage (IVH). Conclusion: This study demonstrates that low PCT predicts IVH, and MPV ≥ 10.2 fL correlates with mortality among infants born after <32 weeks' gestation., (Copyright © 2020 Go, Ohto, Nollet, Takano, Kashiwabara, Chishiki, Maeda, Imamura, Kawasaki, Momoi and Hosoya.)

To date, few studies have investigated whether perinatal factors affect coagulation parameters at birth in preterm and term neonates. We retrospectively investigated coagulation factors on day 1 in 609 consecutive neonates admitted to our neonatal intensive care unit between January 2010 and December 2017. We measured coagulation factors on day 1 using peripheral blood samples. Multivariate analysis revealed that prothrombin time-international normalized ratio correlated with intraventricular hemorrhage ( p  = 0.000; β  = 0.180) and placental abruption (PA; p  = 0.000; β  = 0.142). Activated partial thromboplastin time (aPTT) correlated with birth weight (BW; p  = 0.000; β  =  - 0.217), gestational age (GA; p  = 0.000; β  =  - 0.282), and PA ( p  = 0.000; β  = 0.181). Fibrinogen concentration was associated with respiratory distress syndrome ( p  = 0.007; β  =  - 0.114), pregnancy-induced hypertension ( p  = 0.000; β  =  - 0.141), and Apgar score at 1 minute ( p  = 0.043; β  = 0.147). Furthermore, the level of d-dimer inversely correlated with Apgar score at 5 minutes ( p  = 0.049). Finally, antithrombin III levels positively correlated with GA ( p  = 0.000) and BW ( p  = 0.000). Thus, maternal and neonatal complications affect coagulation parameters in preterm and term neonates., Competing Interests: None declared., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Background: Left ventricular non-compaction (LVNC) is a cardiomyopathy morphologically characterized by 2-layered myocardium and numerous prominent trabeculations, and is often associated with dilated cardiomyopathy (DCM). Variants in the gene encoding tafazzin (TAZ) may change mitochondrial function and cause dysfunction of many organs, but they also contribute to the DCM phenotype in LVNC, and the clinical and echocardiographic features of children with this phenotype are poorly understood., Methods and results: We enrolled 92 DCM phenotype LVNC patients and performed next-generation sequencing to identify the genetic etiology. Ten TAZ variants were identified in 15 male patients (16.3%) of the 92 patients, including 3 novel missense substitutions. The patients with TAZ variants had a higher frequency of early onset of disease (92.3% vs. 62.3%, P=0.0182), positive family history (73.3% vs. 20.8%, P=0.0001), and higher LV posterior wall thickness Z-score (8.55±2.60 vs. 5.81±2.56, P=0.0103) than those without TAZ variants, although the mortality of both groups was similar., Conclusions: This study provides new insight into the impact of DCM phenotype LVNC and emphasizes the clinical advantages available for LVNC patients with TAZ variants.

We investigated the relationship of neonatal and maternal serum creatinine (nSCr and mSCr, respectively) with various maternal/infant characteristics at different gestational ages (GA). We reviewed medical records of neonates admitted to NICU. We collected data on birth weight, GA, Apgar scores, medications, etc. Spearman's test was used to analyze the correlation between serum creatinine and continuous variables, and the Mann-Whitney U and Kruskal-Wallis tests for continuous variables between groups. The changes in nSCr, mSCr, and nSCr/mSCr ratio because of gestational age and the points in gestational changes in trends were estimated using joinpoint trend analysis. From 614 neonate and mother pairs, we found that nSCr was significantly correlated with GA. However, mSCr at >28 wks decreased with GA. The nSCr/mSCr ratio was correlated with GA. In infants born <29 weeks, pregnancy-induced hypertension (PIH) (p = 0.000, β = 0.20) and mSCr (p = 0.000, β = 0.73) were significantly associated with nSCr. In term infants, maternal magnesium administration (p = 0.000, β = 0.25), respiratory distress syndrome (p = 0.013, β = 0.16), PIH (p = 0.005, β = 0.19), and mSCr (p = 0.000, β = 0.33) were significantly associated with nSCr. nSCr reflected mSCr at all gestational ages. The correlation between nSCr and mSCr in preterm infants (p = 0.000, β = 0.74) was stronger than in term infants (p = 0.000, β = 0.34)., Competing Interests: The authors have declared that no competing interests exist.

Background: We hypothesized that gallbladder (GB) volume is affected by serial changes during the early infancy period in extremely premature infants., Methods: We conducted a prospective study of extremely premature infants admitted to the neonatal intensive care unit of Fukushima Medical University Hospital, Fukushima City, Japan between January 2014 and December 2015. GB volume was measured by an abdominal ultrasound ellipsoid method between Day 0 and Day 56 after birth within 60 minutes before enteral feeding. We calculated GB volume (mL)/weight (kg), which was evaluated as GV/W., Results: Intotal, 30 infants were included. Themediangestationalageoftheinfantswas 26 weeks 5 days (range, 23 weeks 1 day-28 weeks 6 days), and the median birth weight was 731 g (range, 398-1220 g). The detection rate of GB decreased in the infants over time; the rates were > 93% between Day 0 and Day 7 and < 77% between Day 10 and Day 56 after birth. GV/W decreased in the infants over time. The median GV/W values were 0.18 (range, 0.05 -0.59) in infants on admission and constantly < 0.05 in those between Day 10 and Day 56 after birth. There was no correlation of GV/W with clinical variables after birth., Conclusion: It is considered that GB volume is not affected by serial changes without nonfavor-able course of enteral nutrition., Competing Interests: Conflicts of interest: The authors have no conflict of interest to declare in relation to this study.

Background: Virus-associated acute encephalopathy (VAE) is a severe central nervous system complication caused by common viral infections in children. The pathophysiology of VAE is thought to be endothelial injury. This study was designed to establish an in vitro VAE model for evaluating endothelial injury caused by the proinflammatory cytokine TNF-α., Methods: Transwell-grown human umbilical vein endothelial cells (HUVECs) monolayers were incubated with serially diluted TNF-α. Transendothelial electrical resistance (TER) was measured using impedance spectroscopy. Permeability changes of HUVECs after TNF-α treatment were determined by fluorescein isothiocyanate (FITC)-conjugated dextran. Moreover, TNF-α-induced morphological changes in claudin-5 and apoptosis were observed by immunofluorescent staining., Results: The decrease in TER, time of TER recovery to baseline, and increase in permeability were all dependent on TNF-α concentration. Immunofluorescent staining showed that claudin-5 was delocalized after TNF-α treatment in a dose-dependent manner. In addition, some apoptotic cells were observed at high TNF-α concentrations., Conclusion: TER measurement combined with a permeability assay could be useful for evaluating vascular endothelial cell permeability in an in vitro model. These evaluation methods will contribute to both the development of specific treatments focusing on vascular permeability, and the search for a novel therapeutic strategy in VAE treatment.

Aim  We determined whether the bacteria in the lower respiratory tract (LRT) in extremely premature infants with severe bronchopulmonary dysplasia (BPD) are different from those with nonsevere BPD. Study Design  We conducted a retrospective study of extremely premature infants who were admitted to the neonatal intensive care unit of Fukushima Medical University Hospital, Japan between April 2005 and March 2014. We screened for the bacterial colonization of the LRT using tracheobronchial aspirate fluid. Results  A total of 169 extremely premature infants were included. Overall, 102 did not experience severe BPD, whereas the remaining 67 experienced severe BPD. Corynebacterium species (Cs) were more frequently detected in the severe BPD than nonsevere BPD infants ( p  = 0.03). There were significant differences between infants with and without severe BPD in the duration of endotracheal ventilation ( p  = 0.00, odds ratio [OR], 1.03; 95% confidence interval [CI], 1.01-1.06), the duration of supplemental oxygen ( p  = 0.00, OR, 1.02; 95% CI, 1.01-1.03) before 36 weeks of postmenstrual age, and the frequency of sepsis after 7 postnatal days ( p  = 0.01, OR, 1.73; 95% CI, 1.18-2.54). Conclusion  Cs are more likely to be present in the severe BPD infants with longer duration of endotracheal ventilation., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

Infants with Down syndrome (DS) are at risk of developing a transient myeloproliferative disorder during the neonatal period, known as transient abnormal myelopoiesis (TAM). It is characterized by clonal myeloproliferation and is typically self-limiting. However, TAM can be a life-threatening disorder, when complicated by liver fibrosis. Here, we evaluated cytokine profiles in two male DS infants having TAM with or without liver dysfunction. The first patient, Patient 1, had hyperleukocytosis with cholestatic liver dysfunction, coagulopathy, and increased counts of blasts and was treated with exchange transfusion (ExT) due to the serious general condition. In Patient 1, serum interleukin (IL)-8 and plasma transforming growth factor (TGF)-β1 levels were markedly elevated before ExT (1,518.2 pg/mL and 17,635 pg/mL, respectively). After ExT, serum IL-8 and plasma TGF-β1 levels decreased to 40.7 pg/mL and 6,847 pg/mL, respectively. However, Patient 1 died on day 56 due to cholestatic liver dysfunction; namely, this patient represents fatal TAM. The second patient, Patient 2, had hyperleukocytosis with increased counts of blasts without liver dysfunction and was treated with cytarabine. In Patient 2, plasma TGF-β1 levels, but not plasma IL-8, were elevated (9,068 pg/mL and 28 pg/mL, respectively). Patient 2 was discharged on day 47. In summary, plasma TGF-β1 levels were elevated in the two DS infants with TAM, regardless of the presence or absence of hepatic fibrosis. Importantly, fatal TAM is assoicated with the elevated serum level of IL-8. We thus propose that IL-8 may be involved in the pathogenesis of liver fibrosis.

A 9-year-old girl developed influenza A H1N1 pdm09-associated myocarditis and pericarditis 2 days after starting zanamivir therapy. The virus was detected in the respiratory tract but not in the serum or pericardial effusion. The virus sampled from the respiratory tract had normal susceptibility to neuraminidase inhibitors. Although no differences in interferon-γ, interleukin (IL)-1β, and tumor necrosis factor-α were observed between the plasma and pericardial effusion, some inflammatory cytokines or chemokines (IL-6 and IL-8) and vascular endothelial growth factor were remarkably elevated in the pericardial effusion compared with the plasma. This suggested that the influenza virus, after infecting the respiratory tract, affected the myocardium, causing myocarditis to gradually develop, which might have been followed by an autoreactive pericarditis causing increased pericardial effusion. Therefore, influenza-associated myocarditis should be considered when influenza patients have respiratory and cardiac involvement, even during treatment with a neuraminidase inhibitor., (© 2015 Japan Pediatric Society.)

Chronic active Epstein-Barr virus (EBV) infection (CAEBV), characterized by persistent infectious mononucleosis-like symptoms, can lead to cardiovascular complications including coronary artery aneurysm or myocarditis. Here, we present the case of an 11-year-old boy with pulmonary arterial hypertension (PAH) and junctional ectopic tachycardia associated with CAEBV. The patient did not have any major symptoms attributed to CAEBV, such as fever, lymphadenopathy or splenomegaly when the PAH developed. Mild liver dysfunction was found at the first examination, and it persisted. Two years after the PAH symptoms appeared, CAEBV was evident, based on deteriorated liver function, hepatosplenomegaly, and coronary artery aneurysms. CAEBV should be considered as a cause of secondary PAH, particularly when liver dysfunction coexists., (© 2015 Japan Pediatric Society.)

Left ventricular noncompaction (LVNC) is a recently defined cardiomyopathy characterized by a pattern of prominent trabecular meshwork and deep intertrabecular recesses. LVNC is rarely described in fetal life, and a small number of cases have been reported. We report the first fetal case, to our knowledge, of LVNC associated with a novel mutation in the MYH7 gene (c.1625A>C; p.Lys542Thr). This patient showed cardiomegaly on prenatal ultrasonographic examinations, with features indicating noncompaction of the myocardium apparent in the second trimester. This case highlights the importance of prenatal ultrasonography for the diagnosis of LVNC and suggests that abnormal myocardial development underlies the pathogenesis of LVNC., (Copyright © 2015 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Hyperammonemia of newborns should be treated promptly, and the outcome depends on the rapid elimination of excessive plasma ammonia. We encountered a case of transient hyperammonemia in an extremely low-birthweight infant whose plasma ammonia decreased sufficiently after continuous hemodialysis therapy. It seems that continuous hemodialysis therapy using the peripheral artery and umbilical vein is useful for hyperammonemia of extremely low-birthweight infants; however, there are several problems to consider due to the immaturity of these infants., (© 2013 The Authors. Pediatrics International © 2013 Japan Pediatric Society.)

Background: Although glucocorticoid hormones play important roles in fetal development, the expression of their receptors in the whole blood of preterm infants remains unknown., Objectives: The aim of this study was to investigate the levels of glucocorticoid receptor (GR) α and β in the whole blood of preterm and term infants., Study Design: The study group consisted of 131 infants, of which 54 (41%) were preterm. Whole blood from preterm and term infants was analyzed by real-time PCR to monitor the levels of each receptor mRNA., Results: GRβ mRNA were detected in 96.6% and GRα mRNA in 100% of participants. The GRα and GRβ isoforms were detected at a ratio of 1:0.0002. GRβ mRNA/GAPDH expression in preterm infants was significantly higher than that in term infants (p=0.002). There was significant correlation between GRα/GRβ ratio and birth weight in preterm infants (rs=0.317, p=0.019), as well as between GRβ/GAPDH expression and birth weight (rs=-0.296, p=0.030). Furthermore, in preterm infants, GRβ/GAPDH expression was higher in those with SGA than in those without SGA (p=0.022)., Conclusion: Importantly, in preterm infants, both the expression of GRβ and the GRα/GRβ ratio were associated with birth weight. Further studies with larger populations are necessary to determine the relation between the expression of GR and the clinical relevance of preterm infants.

Aims: Hypoxia is known to influence cardiovascular (CV) function, in part, through adenosine receptor activation. We have shown in a mouse model that during primary cardiac morphogenesis, acute maternal hypoxia negatively affects fetal heart rate, and recurrent maternal caffeine exposure reduces fetal cardiac output (CO) and downregulates fetal adenosine A(2A) receptor gene expression. In the present study, we investigated whether maternal caffeine dosing exacerbates the fetal CV response to acute maternal hypoxia during the primary morphogenesis period., Material and Methods: Gestational-day-11.5 pregnant mice were exposed to hypoxia (45 s duration followed by 10 min of recovery and repeated 3 times) while simultaneously monitoring maternal and fetal CO using high-resolution echocardiography., Results:   Following maternal hypoxia exposure, maternal CO transiently decreased and then returned to pre-hypoxia baseline values. In contrast to a uniform maternal cardiac response to each exposure to hypoxia, the fetal CO recovery time to the baseline decreased, and CO rebounded above baseline following the second and third episodes of maternal hypoxia. Maternal caffeine treatment inhibited the fetal CO recovery to maternal hypoxia by lengthening the time to CO recovery and eliminating the CO rebound post-recovery. Selective treatment with an adenosine A(2A) receptor antagonist, but not an adenosine A(1) receptor antagonist, reproduced the altered fetal CO response to maternal hypoxia created by caffeine exposure., Conclusions:   Results suggest an additive negative effect of maternal caffeine on the fetal CV response to acute maternal hypoxia, potentially mediated via adenosine A(2A) receptor inhibition during primary cardiovascular morphogenesis., (© 2012 The Authors. Journal of Obstetrics and Gynaecology Research © 2012 Japan Society of Obstetrics and Gynecology.)

Background: The aim of this retrospective study was to evaluate the influence of prenatal diagnosis on perinatal outcomes of congenital heart disease (CHD) over a 17 year period at a single center., Methods: The perinatal outcome of CHD in 146 patients diagnosed on fetal echocardiography between 1994 and 2010 were reviewed. The characteristics of 193 neonatal inpatients with CHD treated at the authors' department between 2001 and 2010 were also analyzed; among the inpatients, 61 were diagnosed before birth (prenatal group) and 132 were diagnosed after birth (postnatal group)., Results: Among the 146 patients prenatally diagnosed with CHD, the prenatal mortality, including abortion and stillbirth, decreased from 1994 to 2010. Among the 193 neonatal inpatients, the prenatal group had lower gestational age and bodyweight than the postnatal group. Further, the prenatal group had lower blood pH at admission, but no patient in that group experienced ductal shock, although six patients in the postnatal group did. The average dose of prostaglandin E1 used in duct-dependent CHD was significantly lower in the prenatal group than in the postnatal group (3.4 vs. 4.6 ng/kg per min; P = 0.015)., Conclusions: Prenatal diagnosis of CHD enables planned labor, prevents ductal shock, and reduces prostaglandin E1 side-effects and medical expenditure., (© 2012 The Authors. Pediatrics International © 2012 Japan Pediatric Society.)

Introduction: Pulmonary interstitial emphysema is a serious complication of mechanical ventilation and can become life-threatening if progression occurs. Therapeutic lung puncture is a treatment option for severe pulmonary interstitial emphysema but has a limited use in babies with extremely low birth weight. We present a case of pulmonary interstitial emphysema in a Japanese baby (1-day-old) boy with extremely low birth weight. The emphysema was successfully decompressed by therapeutic lung puncture performed with a trocar catheter., Case Presentation: The baby was born with a weight of 420g, which, to the best of our knowledge, is the lowest reported birth weight among babies with pulmonary interstitial emphysema. A chest X-ray on postnatal day 2 revealed pulmonary interstitial emphysema, which gradually progressed to diffuse pseudocystic changes. His condition became life-threatening despite the use of high-frequency oscillatory ventilation and lateral decubitus positioning. We evacuated the pulmonary interstitial emphysema by lung puncture with a trocar catheter to avoid respiratory and cardiovascular collapse. This resulted in adequate evacuation of the emphysema and a dramatic improvement in his clinical condition., Conclusions: Therapeutic lung puncture performed with a trocar catheter is beneficial in babies with extremely low birth weight and diffuse pulmonary interstitial emphysema. This treatment option may be broadly applicable, especially in an emergency situation.

Unlabelled: Barth syndrome is an X-linked disorder usually diagnosed in infancy. It is characterized by hypotonia, dilated cardiomyopathy, neutropenia, growth retardation, and 3-methylglutaconic aciduria. The syndrome is typically caused by mutations in the TAZ (G4.5) gene, which encodes a novel protein family called the tafazzins. We report the case of two brothers with Barth syndrome and left ventricular noncompaction (LVNC) caused by a splice donor mutation in TAZ. Both had impaired sucking ability at the age of 2 months. The elder brother was diagnosed with LVNC at the age of 4 months; by that time he had developed severe heart failure with metabolic decompensation. He died at 12 months of age due to intractable heart failure despite pharmacological therapy with diuretics, an angiotensin-converting enzyme inhibitor, and a beta-blocker. However, the younger brother, who was diagnosed as having Barth syndrome and LVNC with heart failure at the age of 2 months, received early medical treatment and demonstrated normal echocardiographic findings., Conclusion: The clinical courses of Barth syndrome observed in our cases show the phonotypic variability of this syndrome and suggest that early therapy may be beneficial for maintaining cardiac function.

Objectives: To evaluate whether peripheral arterial catheter management is more effective than umbilical arterial management in very preterm neonates., Methods: Thirty-eight very preterm neonates born in Fukushima Medical University Hospital between October 2008 and March 2010 were evaluated. A peripheral arterial catheter was inserted in 19 neonates (peripheral group) and an umbilical arterial catheter in the remaining 19 neonates (umbilical group)., Results: The median gestational ages of the peripheral and umbilical groups were 195 and 185 days, respectively (p=0.04). The systolic and diastolic blood pressure (BP) was significantly higher in the peripheral group than in the umbilical group (p=0.03 and p=0.001). There was a significant relationship between BP at cannulation and urinary output after cannulation for 24 h in the peripheral group (r(s)=0.49, p=0.03); however, no such significant relationship was found in the umbilical group., Conclusions: We considered that peripheral artery catheters provide a well-functioning route for continuous BP monitoring, even in very preterm neonates. Because umbilical catheter placement might affect urinary output, we speculated that peripheral arterial catheter placement would be a more effective management strategy than umbilical arterial catheter placement in very preterm neonates. Further studies of larger populations are necessary to evaluate the effectiveness of arterial management including long-term follow-up studies.

Classical citrullinemia generally involves hyperammonemic coma in the first few days of life and leads to neurological sequelae in survivors. We report a case of an elder sister who fell into a hyperammonemic coma on the fifth day after birth. She was successfully treated with intravenous benzoate and hemodialysis, and was subsequently diagnosed with citrullinemia on the basis of biochemical analysis. Two years later, a younger sister was born without prenatal diagnosis. We monitored plasma ammonia and citrulline levels after birth, and again diagnosed her with CTLN1 on the basis of biochemical and DNA analyses. There have been few reports of the prospective treatment of citrullinemia; however, our experience indicates the need for the prospective management and the rapid reduction of ammonia levels to avoid neonatal hyperammonemic coma and subsequent sequelae.

Identification of cells that are endowed with maximum potency could be critical for the clinical success of cell-based therapies. We investigated whether cells with an enhanced efficacy for cardiac cell therapy could be enriched from adult human skeletal muscle on the basis of their adhesion properties to tissue culture flasks following tissue dissociation. Cells that adhered slowly displayed greater myogenic purity and more readily differentiated into myotubes in vitro than rapidly adhering cells (RACs). The slowly adhering cell (SAC) population also survived better than the RAC population in kinetic in vitro assays that simulate conditions of oxidative and inflammatory stress. When evaluated for the treatment of a myocardial infarction (MI), intramyocardial injection of the SACs more effectively improved echocardiographic indexes of left ventricular (LV) remodeling and contractility than the transplantation of the RACs. Immunohistological analysis revealed that hearts injected with SACs displayed a reduction in myocardial fibrosis and an increase in infarct vascularization, donor cell proliferation, and endogenous cardiomyocyte survival and proliferation in comparison with the RAC-treated hearts. In conclusion, these results suggest that adult human skeletal muscle-derived cells are inherently heterogeneous with regard to their efficacy for enhancing cardiac function after cardiac implantation, with SACs outperforming RACs.

Isolated levocardia (IL) is a rare type of situs inversus in which the heart is in the normal left-side position, but the abdominal viscera are in the dextroposition. Polysplenia is a congenital disorder affecting the asymmetric organs, including the heart, lungs, bronchi, liver, stomach, intestines, and spleen. In this report, we present a rare type satisfying the characteristics of both IL and polysplenia, confirmed by several imaging investigations, which revealed normally structured lungs and heart and the existence of the inferior vena cava (IVC), which runs on the left side, returns to the anterior-right side at the liver, and returns to the right atrium directly. Anatomical investigation and careful observation will make it possible to improve the prognosis of IL., (© 2011 The Authors. Congenital Anomalies © 2011 Japanese Teratology Society.)

Objective: To examine the expression levels of glucocorticoid receptor (GR) isoforms in peripheral blood mononuclear cells (PBMCs) and serum cortisol levels in cord blood from term infants., Methods: The study population consisted of 172 term infants who were delivered from healthy pregnant women. GRalpha and GRbeta expression levels, and serum cortisol level in cord blood were determined by real-time PCR and ELISA, respectively., Results: Detection rates of GRalpha, GRbeta, and GAPDH were 100%, 63.4%, and 100%, respectively. The expression level of GRalpha was about 200 times that of GRbeta. There were no associations between GR expression level and clinical variables. There were significant associations of low UmApH, maternal gravidity or parity, and vaginal delivery with a high cortisol level; however, there were no correlations between GR expression levels and cortisol level., Conclusions: It is considered that glucocorticoid effects could be expected from the fetal period to the neonatal period, because GRalpha expression level was not related to perinatal factors, GRbeta expression level, and cortisol level in term infants. Further studies of larger populations including very preterm and small for gestational age infants are necessary to determine the balance of expression between GRalpha and GRbeta, and cortisol level.

Background: In children who have undergone a bidirectional Glenn procedure without antegrade or additional pulmonary blood flow, we have often noted a discrepancy between apparent lung perfusion on scintigraphy and superior vena cava angiography when evaluating right and left pulmonary blood flow. We found a tendency for radionuclide, tracer 99mTc-MAA, when administered through a single upper extremity vein, to preferentially accumulate in the ipsilateral lung., Objective: In the present study, we examined whether the ratio of right-to-left pulmonary flow varied when 99mTc-MAA was administered via either the right upper or the left upper extremity vein., Materials and Methods: We studied six children (median age 1.3 ± 0.23 years) who underwent a bidirectional Glenn before total cavopulmonary connection. Five children who underwent biventricular repair served as a control. Perfusion scintigraphy using 99mTc-labeled macroaggregated albumin (99mTc-MAA) was performed in all children. First, we injected radionuclide via the right upper extremity and calculated the pulmonary accumulation in both lungs (R-image). Second, we injected the same dose of radionuclide via the left upper extremity and calculated the pulmonary accumulation (B-image), which represented the resulting administration via both upper extremities. The lung accumulation that resulted from radionuclide administration via the left upper extremity (L-image) was determined by subtracting the R-image from the B-image. We evaluated the right-to-total pulmonary blood flow ratio (radionuclide accumulation in right lung / radionuclide accumulation in both lungs) in the R-, L- and B-images., Results: The right-to-total pulmonary blood flow ratios in the R-, L- and B-images were 815 ± 15.3%, 39.8 ± 11.7% and 61.3 ± 11.8%, respectively, and there were significant differences among the three images (P < 0.01). On the other hand, in the control group, the right-to-total pulmonary blood flow ratios in the R-, L- and B-images were 59.3 ± 22.4%, 57.8 ± 26.4% and 58.8 ± 23.7%, respectively, and there was no significant difference., Conclusion: In children with bidirectional Glenn circulation without antegrade or additional pulmonary blood flow, the venous blood of each arm tends to flow into the ipsilateral lung. The administration of radionuclide via both arms is important for accurate evaluation of lung perfusion scintigraphy in children who have undergone a bidirectional Glenn procedure.

Injectable biomaterials have been recently investigated as a therapeutic approach for cardiac repair. Porcine-derived small intestinal submucosa (SIS) material is currently used in the clinic to promote accelerated wound healing for a variety of disorders. In this study, we hypothesized that gels derived from SIS extracellular matrix would be advantageous as an injectable material for cardiac repair. We evaluated 2 forms of SIS gel, types B (SIS-B) and C (SIS-C), for their ability to provide a therapeutic effect when injected directly into ischemic myocardium using a murine model of an acute myocardial infarction. Echocardiography analysis at both 2 and 6 weeks after infarction demonstrated preservation of end-systolic left ventricular geometry and improvement of cardiac contractility in the hearts injected with SIS-B when compared with control hearts injected with saline. However, the SIS-C gel provided no functional efficacy in comparison with control. Histological analysis revealed that SIS-B reduced infarct size and induced angiogenesis relative to control, whereas injection of SIS-C had minimal effect on these histological parameters. Characterization of both gels revealed differential growth factor content with SIS-B exhibiting higher levels of basic fibroblast growth factor than SIS-C, which may explain, at least in part, the differential histological and functional results. This study suggests that SIS gel offers therapeutic potential as an injectable material for the repair of ischemic myocardium. Further understanding of SIS gel characteristics, such as biological and physical properties, that are critical determinants of efficacy would be important for optimization of this biomaterial for cardiac repair., (Copyright 2010 Elsevier Ltd. All rights reserved.)

TAZ (G4.5) was initially identified as the gene associated with Barth syndrome and left ventricular noncompaction (LVNC). The purpose of this study was to investigate patients with LVNC for disease-causing mutations in TAZ. In 124 Japanese patients, including 50 families, mutation analysis of TAZ was performed using DNA sequencing. A splice donor mutation was identified in two brothers with Barth syndrome and LVNC, and a sister who was asymptomatic. However, the variant was not identified in either parent or the maternal grandparents, all of whom were asymptomatic. Due to the recurrent inheritance of this variant by each of the children we concluded that this was evidence of gonadal mosaicism in the obligate carrier mother, the first reported occurrence of this in Barth syndrome.

Objectives: The aim of this study was to evaluate the therapeutic potential of human skeletal muscle-derived myoendothelial cells for myocardial infarct repair., Background: We have recently identified and purified a novel population of myoendothelial cells from human skeletal muscle. These cells coexpress myogenic and endothelial cell markers and produce robust muscle regeneration when injected into cardiotoxin-injured skeletal muscle., Methods: Myoendothelial cells were isolated from biopsies of human skeletal muscle using a fluorescence-activated cell sorter along with populations of regular myoblasts and endothelial cells. Acute myocardial infarction was induced in male immune-deficient mice, and cells were directly injected into the ischemic area. Cardiac function was assessed by echocardiography, and donor cell engraftment, angiogenesis, scar tissue, endogenous cardiomyocyte proliferation, and apoptosis were all evaluated by immunohistochemistry., Results: A greater improvement in left ventricular function was observed after intramyocardial injection of myoendothelial cells when compared with that seen in hearts injected with myoblast or endothelial cells. Transplanted myoendothelial cells generated robust engraftments within the infarcted myocardium, and also stimulated angiogenesis, attenuation of scar tissue, and proliferation and survival of endogenous cardiomyocytes more effectively than transplanted myoblasts or endothelial cells., Conclusions: Our findings suggest that myoendothelial cells represent a novel cell population from human skeletal muscle that may hold promise for cardiac repair.

Caffeine consumption during pregnancy is reported to increase the risk of in utero growth restriction and spontaneous abortion. In the present study, we tested the hypothesis that modest maternal caffeine exposure affects in utero developing embryonic cardiovascular (CV) function and growth without altering maternal hemodynamics. Caffeine (10 mg.kg(-1).day(-1) subcutaneous) was administered daily to pregnant CD-1 mice from embryonic days (EDs) 9.5 to 18.5 of a 21-day gestation. We assessed maternal and embryonic CV function at baseline and at peak maternal serum caffeine concentration using high-resolution echocardiography on EDs 9.5, 11.5, 13.5, and 18.5. Maternal caffeine exposure did not influence maternal body weight gain, maternal CV function, or embryo resorption. However, crown-rump length and body weight were reduced in maternal caffeine treated embryos by ED 18.5 (P < 0.05). At peak maternal serum caffeine concentration, embryonic carotid artery, dorsal aorta, and umbilical artery flows transiently decreased from baseline at ED 11.5 (P < 0.05). By ED 13.5, embryonic aortic and umbilical artery flows were insensitive to the peak maternal caffeine concentration; however, the carotid artery flow remained affected. By ED 18.5, baseline embryonic carotid artery flow increased and descending aortic flow decreased versus non-caffeine-exposed embryos. Maternal treatment with the adenosine A(2A) receptor inhibitor reproduced the embryonic hemodynamic effects of maternal caffeine exposure. Adenosine A(2A) receptor gene expression levels of ED 11.5 embryo and ED 18.5 uterus were decreased. Results suggest that modest maternal caffeine exposure has adverse effects on developing embryonic CV function and growth, possibly mediated via adenosine A(2A) receptor blockade.

Objectives: We investigated whether vascular endothelial growth factor (VEGF) was associated with the angiogenic and therapeutic effects induced after transplantation of skeletal muscle-derived stem cells (MDSCs) into a myocardial infarction (MI)., Background: Because very few MDSCs were found to differentiate into new blood vessels when injected into the heart, the mechanism underlying the occurrence of angiogenesis after MDSC transplantation is currently unknown. In the present study, we used a gain- or loss-of-VEGF function approach with skeletal MDSCs engineered to express VEGF or soluble Flt1, a VEGF-specific antagonist, to identify the involvement of VEGF in MDSC transplantation-induced neoangiogenesis., Methods: Vascular endothelial growth factor- and soluble Flt1-engineered MDSCs were injected into an acute MI. Angiogenesis and cardiac function were evaluated by immunohistochemistry and echocardiography., Results: Both control and VEGF-overexpressing MDSCs induced angiogenesis, prevented adverse cardiac remodeling, and improved function compared with saline-injected hearts. However, these therapeutic effects were diminished in hearts transplanted with MDSCs expressing soluble Flt1 despite successful cell engraftment. In vitro experiments demonstrated that MDSCs increased secretion of VEGF in response to hypoxia and cyclic stretch (likely conditions in ischemic hearts), suggesting that transplanted MDSCs release VEGF in vivo., Conclusions: Our findings suggest that VEGF is essential for the induction of angiogenesis and functional improvements observed after MDSC transplantation for infarct repair.

Objectives: Our objective in this study was to apply an elastic, biodegradable polyester urethane urea (PEUU) cardiac patch onto subacute infarcts and to examine the resulting cardiac ventricular remodeling and performance., Background: Myocardial infarction induces loss of contractile mass and scar formation resulting in adverse left ventricular (LV) remodeling and subsequent severe dysfunction., Methods: Lewis rats underwent proximal left coronary ligation. Two weeks after coronary ligation, a 6-mm diameter microporous PEUU patch was implanted directly on the infarcted LV wall surface (PEUU patch group, n = 14). Sham surgery was performed as an infarction control (n = 12). The LV contractile function, regional myocardial wall compliance, and tissue histology were assessed 8 weeks after patch implantation., Results: The end-diastolic LV cavity area (EDA) did not change, and the fractional area change (FAC) increased in the PEUU patch group (p < 0.05 vs. week 0), while EDA increased and FAC decreased in the infarction control group (p < 0.05). The PEUU patch was largely resorbed 8 weeks after implantation and the LV wall was thicker than infarction control (p < 0.05 vs. control group). Abundant smooth muscle bundles with mature contractile phenotype were found in the infarcted myocardium of the PEUU group. The myocardial compliance of the PEUU group was distributed between normal myocardium and infarction control (p < 0.001)., Conclusions: Implantation of a novel biodegradable PEUU patch onto a subacute myocardial infarction promoted contractile phenotype smooth muscle tissue formation and improved cardiac remodeling and contractile function at the chronic stage. Our findings suggest a new therapeutic option against post-infarct cardiac failure.

Newborn animals are more resistant to anoxia than older animals, partly due to an increased tolerance of the immature heart to anoxia. Newborn animals also have a more robust preterminal gasp. We investigated the relationship between gasping and cardiac function in immature and maturing rats exposed to anoxia. Immature postnatal day 7 (PND7) rats (n = 13) and maturing PND17 rats (n = 13) were exposed to 100% nitrogen (anoxia) for 10 min. Echocardiography was used to calculate cardiac contractility (CC) by left ventricular shortening fraction and cardiac output (CO) from Doppler velocity recordings of pulmonary artery blood flow. In a separate group of PND7 rats, CC and CO were recorded after the paralytic agent pancuronium was used to prevent gasping. Anoxia decreased CC and CO in PND7 and PND17 rats, followed by a partial and transient recovery. Gasping preceded recovery of CO and was required to sustain CO. Gasping in PND7 rats lasted longer (541 s versus 351 s, p < 0.01) and resulted in a greater recovery of CC and CO. Anoxia-induced gasping and the associated recovery of cardiac function were abolished by paralysis. Thus, anoxia-induced gasping transiently improves cardiac function, and more robust gasping in immature rats is associated with increased cardiac anoxic tolerance.

Using the whole-cell voltage clamp technique, we investigated the effects of thiopental on membrane currents in H9c2 cells, a cell line derived from embryonic rat heart. Thiopental blocked a rapidly activating, very slowly-inactivating ultra-rapid type I(Kur)-like outward K(+) current in a concentration-dependent manner. The half-maximal concentration (IC(50)) of thiopental was 97 microM with a Hill coefficient of 1.2. The thiopental-sensitive current was also blocked by high concentrations of nifedipine (IC(50) = 9.1 microM) and 100 microM chromanol 293B, a blocker of slowly activating delayed rectifier K+ current (I(Ks)), but was insensitive to E-4031, an inhibitor of rapidly activating delayed rectifier K(+) current (I(Kr)). TEA (tetraethylammonium) at 5 mM and 4-AP (4-aminopiridine) at 1 mM reduced the K(+) current to 30.8 +/- 12.2% and 20.5 +/- 6.5% of the control, respectively. Using RT-PCR, we detected mRNAs of Kv2.1, Kv3.4, Kv4.1, and Kv4.3 in H9c2 cells. Among those, Kv2.1 and Kv3.4 have I(Kur)-type kinetics and are therefore candidates for thiopental-sensitive K(+) channels in H9c2 cells. This is the first report showing that thiopental inhibits I(Kur). This effect of thiopental may be involved in its reported prolongation of cardiac action potentials.