The outcome of the surgical repair of multiple ventricular septal defects was satisfactory. Although the sandwich technique is simple and effective, the use of numerous felt patches disturbed the movement of the interventricular septum. An effort should be made to close the muscular ventricular septal defect directly to avoid postoperative cardiac dysfunction. Large apical ventricular septal defects, especially those located just underneath the moderator band, are considered suitable for the sandwich technique.
Regenerative therapy is a new strategy for the end-stage heart failure; however, the ideal cell source has not yet been established for this therapy. We expected that the amnion might be an ideal cell source for cardiac regenerative therapy and that the differentiation potency of the human amnion mesenchymal cells (hAMCs) could be improved by overexpression of Oct4, a key factor that maintains the undifferentiated state. A plasmid vector was made by insertion of the Oct4 open reading frame (ORF) under control of a cytomegalovirus (CMV) promoter (pCMV-hOct4) and transfected into hAMCs by electroporation. The optimum induction time was investigated by comparing the quantity of stem cell-specific mRNAs, cardiac-specific mRNAs, and cardiac-specific proteins with time. hAMCs already expressed cardiac-specific proteins such as Nkx2.5 and Connexin43. After pCMV-hOct4 transfection, endogenous Oct4 mRNA and other stem cell markers showed a transient increase. With 5-azacytidine treatment, quantities of the cardiac-specific mRNAs, such as GATA4 and myosin light-chain-2v (Mlc-2v), were increased significantly. After Oct4 overexpression, the highest expression of cardiac-specific mRNAs and stem cell makers was seen at almost the same time. Furthermore, more mature myocardial contraction proteins were observed when hAMCs were induced at specific optimal times after gene transfection. In conclusion, hAMCs were activated to an undifferentiated state by overexpression of Oct4, and their cardiac differentiation potency was improved. Thus, the single-time transfection of the Oct4 expression vector may be a useful strategy for effective cell therapy. The use of cryopreserved hAMCs in cell therapy still requires more investigation.
Adult cardiomyocytes have little ability to regenerate, thus cardiac regeneration therapy represents a potential method for treating severe heart failure. Human amniotic mesenchymal cells (hAMCs) have the potential to be a useful cell source for cardiac regeneration therapy. We attempted to isolate stem cells from hAMCs and differentiate them into cardiomyocytes. Nanog promoter-Cre plasmid and cytomegalovirus (CMV) promoter-loxP-STOP-loxP-Red-puro(r) plasmid were co-transfected into immortalized hAMCs (iHAMs). Nanog-positive iHAMs were treated with 5-azacytidine (5-aza), trichostatin A (TA), activin A (AA), and bone morphogenetic protein-4 (BMP-4), or co-cultured with murine fetal cardiomyocytes for cardiomyocytes differentiation. Isolated Nanog-positive iHAMs were analyzed by quantitative RT-PCR and immunofluorescent staining before and after differentiation. Expression of Nanog, Oct3/4, Sox2, and Klf4 was significantly higher in Nanog-positive than in Nanog-negative iHAMs. Nanog-positive iHAMs were stained for Nanog and Oct3/4 in the nucleus. Nanog-positive iHAMs treated with 5-aza expressed Nkx2.5, GATA-4, human atrial natriuretic peptide (hANP), cardiac troponin T (cTnT), myocin light chain (Mlc)-2a, Mlc-2v, β-myosin heavy chain (β-MHC), hyperpolarization-activated cyclic nucleotide gated channels (HCN)-4, and inwardly rectifying potassium channels (Kir)-2.1. Although Nanog-positive iHAMs treated with TA, AA, or BMP-4 expressed several cardiac markers, no contraction was observed. Co-cultured Nanog-positive iHAMs with murine fetal cardiomyocytes spontaneously contracted in a synchronized manner and expressed the cardiac markers. In conclusion, Nanog-positive hAMCs with characteristics of stem cells were isolated and differentiated into cardiomyocyte-like cells, suggesting that these isolated hAMCs could be a useful cell source for cardiac regeneration therapy.
A two-month-old male infant with tetralogy of Fallot underwent a right-sided modified Blalock-Taussig shunt using a 4 mm expanded polytetrafluoroethylene graft through a right thoracotomy. Five months later, the patient developed otitis media, followed by repeated relapses of pneumonia and fever of unknown origin. Multidetector-row computed tomography and angiography, performed at 12 months of age, revealed a pseudoaneurysm of the subclavian artery at the insertion of the modified Blalock-Taussig shunt. After 20 days of antibiotic therapy, the pseudoaneurysm and infected graft were successfully resected through a median sternotomy approach. This report describes the treatment strategy of this rare but potentially fatal complication after a modified Blalock-Taussig shunt operation.
ereditary spherocytosis (HS) is a genetically determined red blood cell membrane disorder that results in hemolytic anemia. 1 There are only a few case reports of patients with HS who have undergone open heart surgery. [2][3][4][5][6][7][8][9] Theoretically, these patients have a high risk of perioperative hemolysis and secondary renal dysfunction attributable to the deleterious effects of cardiopulmonary bypass (CPB). Because limited information is available concerning such operations for patients with HS, we report the findings of an 18-month-old child with congenital heart disease and HS. Case ReportA 5-month-old girl was referred to hospital after a diagnosis of ventricular septal defect (VSD) and pulmonary stenosis (PS). She was suspected to have HS because her father and grandmother were known to have suffered from HS. Her red blood cells showed increased osmotic fragility, and a diagnosis of HS was made. At the ages of 7 and 17 months, 10 ml/kg of packed red blood cells were transfused in order to treat the progressive anemia. Gradually, the pressure gradient between the right ventricle and pulmonary artery decreased, and left ventricular volume increased (Table 1). On admission, the patient was anemic and icteric. She weighed 11.9 kg. Physical examination revealed a systolic ejection murmur at the left second intercostal space and splenomegaly. Hematologic investigation revealed a hemoglobin level of 7.2 g/dl, and reticulocyte count of 36.8%. The total bilirubin level was 2.8 mg/dl (Table 2). Two-dimensional echocardiography showed a large perimembranous VSD with left-to-right shunt, and valvular and supravalvular PS. The pulmonary annulus measured 12 mm and the main pulmonary trunk measured 6 mm. Circulation Journal Vol.70, December 2006Echocardiography also showed non-compaction of the left ventricular muscle. Cardiac catheterization confirmed the left-to-right shunt, with a ratio of pulmonary blood to systemic blood flow (Qp/Qs) of 1.78:1. The left ventricle was dilated to 195% of the normal volume, but overall left ventricular function was normal. Central venous pressure and pulmonary capillary wedge pressure was 9 mmHg and 13 mmHg, respectively. The systolic pressure gradient between the right ventricle and distant main pulmonary trunk was 49 mmHg. Although open heart surgery using CPB has the risk of hemolytic crisis, the most recent reports 5,7 suggest that the results for patients with HS without splenectomy are acceptable. Therefore, the patient was scheduled for open heart surgery at the age of 18 months. Her parents were informed of the purpose and risk of the surgical treatment, and they gave written informed consent.She underwent closure of the VSD, commissurotomy of the pulmonary valve, and patch angioplasty of the pulmonary trunk using autologous pericardium. The CPB circuit consisted of a roller pump and a membrane oxygenator, and the CPB time was 150 min. In order to maintain the hematocrit level and osmotic pressure of the priming solution, 150 ml of packed red blood cells and 20 ml of ...
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