Comparison of adipose tissue- and bone marrow- derived mesenchymal stem cells for alleviating doxorubicin-induced cardiac dysfunction in diabetic rats.

INTRODUCTION: Doxorubicin (DOX) is a well-known anticancer drug. However its clinical use has been limited due to cardiotoxic effects. One of the major concerns with DOX therapy is its toxicity in patients who are frail, particularly diabetics. Several studies suggest that mesenchymal stem cells (MSCs) have the potential to restore cardiac function after DOX-induced injury. However, limited data are available on the effects of MSC therapy on DOX-induced cardiac dysfunction in diabetics. Our objective was to test the efficacy of bone marrow-derived (BM-MSCs) and adipose-derived MSCs (AT-MSCs) from age-matched humans in a non-immune compromised rat model. METHODS: Diabetes mellitus was induced in rats by streptozotocin injection (STZ, 65 mg/kg b.w, i.p.). Diabetic rats were treated with DOX (doxorubicin hydrochloride, 2.5 mg/kg b.w, i.p) 3 times/wk for 2 weeks (DOX group); or with DOX+ GFP labelled BM-MSCs (2x106cells, i.v.) or with DOX + GFP labelled AT-MSCs (2x106cells, i.v.). Echocardiography and Langendorff perfusion analyses were carried out to determine the heart function. Immunostaining and western blot analysis of the heart tissue was carried out for CD31 and to assess inflammation and fibrosis. Statistical analysis was carried out using SPSS and data are expressed as mean ± SD. RESULTS: Glucose levels in the STZ treated groups were significantly greater than control group. After 4 weeks of intravenous injection, the presence of injected MSCs in the heart was confirmed through fluorescent microscopy and real time PCR for ALU transcripts. Both BM-MSCs and AT-MSCs injection prevented DOX-induced deterioration of %FS, LVDP, dp/dt max and rate pressure product. Staining for CD31 showed a significant increase in the number of capillaries in BM-MSCs and AT-MSCs treated animals in comparison to DOX treated group. Assessment of the inflammation and fibrosis revealed a marked reduction in the DOX-induced increase in immune cell infiltration, collagen deposition and αSMA in the BM-MSCs and AT-MSCs groups. CONCLUSIONS: In conclusion BM-MSCs and AT-MSCs were equally effective in mitigating DOX-induced cardiac damage by promoting angiogenesis, decreasing the infiltration of immune cells and collagen deposition.

Transcatheter closure of secundum ASD using Occlutech Figulla-N device in symptomatic children younger than 2 years of age.

INTRODUCTION: Atrial septal defect (ASD) transcatheter occlusion techniques have become alternatives to surgical procedures. We evaluated the efficiency and safety of the Occlutech Figulla-N device in percutaneous closure of secundum ASDs in symptomatic children younger than 2 years of age. METHODS: The study included 17 patients (9 girls, 8 boys; mean age, 10.3 ± 2.1 months). Mean weight was 7.4 ± 1.3 kg, with secundum ASDs measuring more than 8 mm with a hemodynamically significant shunt, resulting in failure to thrive, right ventricular dilatation, and pulmonary hypertension. Two girls had fenestrated ASD secundum. Defect size and total interatrial septal length were estimated by transthoracic (TTE) and transesophageal (TEE) echocardiography in 3 views. Procedures were performed under fluoroscopic and TEE guidance. Patients were followed-up at 1, 3, 6, and 12 months with TTE. RESULTS: The mean defect size was 15.4 ± 2.7 mm on TTE and 17.1 ± 1.9 mm on TEE. The mean device size was 17.8 ± 3.6 mm (range, 10 to 24 mm). The mean pulmonary artery pressure was 54 ± 18 mm Hg. The device was placed successfully in all patients including fenestrated ASDs that were closed with a single device placement. No residual flow was seen after device placement in patients. Complications were seen in 2/17 patients (11.8%) in the form of sinus tachycardia in 1 patient and femoral vein hematoma in 1 patient. At 6 and 12 months, all the patients were asymptomatic. No cardiac perforation, device erosion, embolization, thrombus formation, or malposition of the device was observed. Three patients developed mild insignificant mitral regurgitation. CONCLUSIONS: ASD closure in severely symptomatic children younger than 2 years of age using the Occlutech Figulla-N occluder is safe and efficient. Meticulous care to patient selection, adequate defect sizing, and device size selection are keys to lower incidence of complications.

Balloon angioplasty for native aortic coarctation in children and infants younger than 12 months: immediate and medium-term follow-up.

BACKGROUND: Despite more than 20 years of experience, balloon angioplasty as treatment for native coarctation of the aorta (CoA) during childhood remains controversial. METHODS AND RESULTS: Fifty-three pediatric patients with discrete native coarctation for whom balloon angioplasty (BA) was performed were included in this study. Patients were divided into 3 groups: group A patients, ≤3 months of age (n = 20); group B patients, between 4-12 months of age (n = 15); and group C patients, between 1 and 12 years (n = 18). Mean age at BA was 0.9 months for group A, 6.5 months for group B, and 7.8 years for group C. The mean body weight was 4.2 kg for group A, 8.6 kg for group B, and 15.3 kg for group C. Successful BA was achieved in 48 of 53 patients (90.6%). Follow-up revealed re-coarctation in 13/53 patients (24.5%); 6 patients with restenosis were referred for surgery, and 7 underwent a second BA procedure. At the end of the study period, BA was effective in 88.7% of patients. The incidence of peripheral vascular complications following BA was higher in group A (17%). Aneurysms were detected in 3/20 (15%) in group A and 2/15 (13.3%) in group B. CONCLUSIONS: BA is a safe and effective treatment for native aortic coarctation. Due to the risk of aneurysm formation in children, cautious selection of patients, the use of low-profile balloons, and state-of-the-art postoperative care are imperative to improve patient outcomes and decrease the risk of complications.

Percutaneous closure of medium and large PDAs using amplatzer duct occluder (ADO) I and II in infants: safety and efficacy.

BACKGROUND: The use of the Amplatzer duct occluder (ADO; AGA Medical Corporation) is well established and reported in children and adults, but there are only occasional reports on use in symptomatic infants. METHODS AND RESULTS: Between March 2009 and January 2011, a group of 47 infants less than 2 years of age with symptomatic patent ductus arteriosus (PDA) was treated using ADO I and II devices. Patients were divided into infants less than 1 year old (group A; n = 28/47; 59.6%) and children between 1 and 2 years old (group B; n = 19/47; 40.4%). Physical examinations and echocardiograms were performed before the procedure and at follow-up (3, 6, and 12 months). Mean age was 5.3 ± 2.3 months for group A and 12.6 ± 1.7 months for group B. Mean weight at closure was 4.8 ± 1.9 kg for group A and 7.3 ± 2.1 kg for group B. ADO I was deployed in 19/28 of group A (67.9%) and 16/19 of group B (84.2%). ADO II was used in 9/28 of group A (32.1%) and 3/19 of group B (15.8%). No residual shunt at the end of the procedure was detected by angiography in any of the cases closed with ADO I and only 3/12 (25%) closed with ADO II showed a minimal residual flow. No mortality or major complications occurred. Six months after closure, weight gain, control of respiratory infections, and regression of left ventricular dilatation with improved systolic function were observed. CONCLUSIONS: Percutaneous closure of moderate to large PDAs using ADO I and II devices in infants and children younger than 2 years of age is safe and effective.

Association of tumor necrosis factor-alpha polymorphisms with susceptibility and clinical outcomes of rheumatic heart disease.

OBJECTIVE: To examine the association of tumor necrosis factor-alpha (TNF-alpha) gene polymorphisms with rheumatic heart disease (RHD) and valve damage, and their influence on TNF-alpha production and disease outcome. METHODS: We performed this cross-sectional study at Kasr El-Aini Hospital, Cairo University, Cairo, Egypt, from December 2008 to October 2009. Eighty children with chronic RHD and valve affection, and 50 controls were included. Patients with any other diseases or complications were excluded. Blood samples (5 ml) were collected. Genotyping for TNF-alpha polymorphisms was performed by the polymerase chain reaction-restriction fragment length polymorphism method. Serum TNF-alpha was measured by enzyme-linked immunosorbent assay. RESULTS: Serum TNF-alpha was significantly increased in RHD compared with controls (p=0.00003). The TNF-alpha -238 adenine (AA) (p=0.036) and -308AA (p=0.003) genotypes were more frequent in RHD patients than in controls, and were associated with increased production of TNF-alpha (p=0.00001 for 238AA) and (p=0.001 for 308AA). Both polymorphisms contributed to increased susceptibility for RHD (-308AA and adenine guanine (AG), odds ratio [OR]=4.72 [95% confidence interval [CI] 2.03-11.05], p=0.0001); (-238 AA and AG, OR=2.33 [CI: 1.05-5.19], p=0.035). The presence of -308AA was associated with mitral (p=0.001) and multivalvular (p=0.003) lesions and was more prevalent in moderate (p=0.001), and severe (p<0.001) cases than in controls. The -238AA variant was associated with mitral lesions (p=0.04) and severe cases (p=0.05) as compared with controls. CONCLUSION: The TNF-alpha-238G/A and -308G/A polymorphisms were associated with susceptibility to RHD and increased production of TNF-alpha. Both polymorphisms were related to valve damage, and a more severe outcome of RHD.

Diagnostic dilemma of cardiac syncope in pediatric patients.

AIMS: Syncope is defined as temporary loss of consciousness and postural tone resulting from an abrupt transient decrease in cerebral blood flow. The present work aimed at determining how diagnostic tests are used in the evaluation of pediatric syncope at a tertiary pediatric referral center and to report on the utility and the yield of these tests. SETTINGS AND DESIGN: Retrospective study conducted at a tertiary referral arrhythmolology service METHODS AND MATERIAL: The clinical charts of 234 pediatric patients presenting with a primary complaint of syncope with an average age of 7.48 +/- 3.82(3.5-16) years were reviewed by the investigators. STATISTICAL ANALYSIS USED: Statistical Package of social science (SPSS) version 9,0 was used for analysis of data. RESULTS: The commonest trigger for syncope in the study population was early following exercise (n=65) and the commonest prodrome was palpitation, noted in 25 patients. A murmur was present in 19 of our patients (8.3%) while 10.7% (n=25) had abnormal ECGs. Of the 106 echocardiograms done, 14 (13.2%) were abnormal. Only two of them were missed by ECG. All patients were offered ambulatory 24 hour ECG. One patient with sick sinus syndrome was diagnosed only with Holter. CONCLUSIONS: Clues to the presence of cardiac syncope may include acute onset of syncope, frequent episodes, low difference between blood pressure readings in supine and erect positions (after standing for 2 minutes) and most importantly an abnormal 12 lead ECG. Transthoracic echo and Holter monitoring have low yield in pediatric syncope.