Effects of domperidone on QTc interval in infants.

AIM: To prospectively evaluate the effects of oral domperidone on the QTc interval in infants. METHODS: Infants (0-1 year) with a diagnosis of gastro-oesophageal reflux (GOR) disease were included. A 12-lead electrocardiography (ECG) was performed in all infants at baseline and 1 h after the intake of domperidone after 7-14 days; the corrected QTc interval was calculated by one investigator (MV) according to Bazett's formula. RESULTS: Forty-five infants were enrolled in this study. The mean gestational age was of 38.6 weeks (35.5-42.0), and the mean age at the start of domperidone was 75.3 days (19-218 days). No statistically significant difference in corrected QTc was observed between baseline and the second ECG (0.389 ± 0.02 vs. 0.397 ± 0.31; p 0.130)). A trend was observed regarding gender: Although there was no difference in QTc change in girls (p 0.622), there was a strong trend in boys (p 0.051). Two infants (both boys) had a clinically significant QTc prolongation (> 460 msec) without symptoms. The Spearman correlation test showed no relation between the QTc change and age (r: -0.05822; p 0.7284). There was no relation between domperidone dosage and QTc change. CONCLUSION: Overall, the group-analysis showed no statistical significant difference in QTc duration induced by domperidone. However, 2/45 (4.4%) infants had a prolonged QTc interval (> 460 msec) induced by domperidone. As a consequence, QTc measurement should be recommended in routine in infants when domperidone is started.

Functional outcome of bone marrow stem cells: mononuclear versus mesenchymal stem cells after cellular therapy in myocardial scar in Wistar rats.

Experimental studies have suggested that a bone marrow stem cell transplant into the heart produces a favorable impact on tissue perfusion, yielding a new perspective on myocardial regeneration. Studies in human beings have demonstrated an improved clinical and functional cardiac state, which has been explained mainly by the angiogenic potential of the stem cells. Our objective was to compare the functional outcome of mononuclear stem (MoSC) and mesenchymal stem (MeSC) cell therapy after myocardium infarction in rats. Forty-two rats with myocardial infarctions underwent autologous transplantation of MoSC and MeSC in animals with ejection fractions lower than 40%. The functional analysis was performed using echocardiography at baseline and at 1 month after direct injection into the ventricular wall using: 5 x 10(6) MoSC (n = 08) or 2.5 x 10(6) MeSC (n = 13) or medium controls (n = 21). Statistical significance was accepted when P < .05. Intragroup comparisons of baseline versus 1-month follow-up were performed with paired t tests. Kruskal-Wallis was used as appropriate. There was a difference in baseline left ventricular ejection fraction (LVEF) and left ventricular-end dyastolic volume between all groups. After 1 month, LVEF decreased in the control group but remained unchanged in MoSC and MeSC groups. In all groups we observed myocardial remodeling. In conclusion, we have not demonstrated functional effectiveness with either MoSC or MeSC cell type, but potentially improved myocardial perfusion needs to be analyzed.

Simultaneous autologous transplantation of cocultured mesenchymal stem cells and skeletal myoblasts improves ventricular function in a murine model of Chagas disease.

BACKGROUND: Cellular transplantation is emerging as a promising strategy for the treatment of postinfarction ventricular dysfunction. Whether its beneficial effects can be extended to other cardiomyopathies remains an unexplored question. We evaluated the histological and functional effects of simultaneous autologous transplantation of co-cultured stem cells and skeletal myoblasts in an experimental model of dilated cardiomyopathy caused by Chagas disease, characterized by diffuse fibrosis and impairment of microcirculation. METHODS AND RESULTS: Wistar rats weighing 200 grams were infected intraperitoneally with 15 x 10(4) trypomastigotes. After 8 months, 2-dimensional echocardiographic study was performed for baseline assessment of left ventricle (LV) ejection fraction (EF) (%), left ventricle end-diastolic volume (LVEDV) (mL), and left ventricle end-systolic volume (LVESV) (mL). Animals with LV dysfunction (EF <37%) were selected for the study. Autologous skeletal myoblasts were isolated from muscle biopsy and mesenchymal stem cells from bone marrow aspirates were co-cultured in vitro for 14 days, yielding a cell viability of >90%. Eleven animals received autologous transplant of 5.4 x 10(6)+/-8.0 x 10(6) cells (300 microL) into the LV wall. The control group (n=10) received culture medium (300 microL). Cell types were identified with vimentin and fast myosin. After 4 weeks, ventricular function was reassessed by echo. For histological analysis, heart tissue was stained with hematoxylin and eosin and immunostained for fast myosin. After 4 weeks, cell transplantation significantly improved EF and reduced LVEDV and LVESV. No change was observed in the control group. CONCLUSIONS: The co-transplant of stem cells and skeletal myoblasts is functionally effective in the Chagas disease ventricular dysfunction.

Cell transplantation after the coculture of skeletal myoblasts and mesenchymal stem cells in the regeneration of the myocardium scar: an experimental study in rats.

UNLABELLED: In myocardial infarction and Chagas's disease, some physiopathological aspects are common: cardiomyocyte loss due to ischemia leads to a reduction of contractility and heart function. Different cells have been proposed for cellular cardiomioplasty. OBJECTIVE: Our goal was to evaluate the method of co-culture of skeletal muscle (SM) and mesenchymal stem cells (MSC) for cell therapy of heart failure in Chagas's disease (CD) and myocardium postinfarction (MI). METHODS: For MI, 39 rats completed the study at 1 month. Seventeen rats received cell therapy into the scar and 22 rats only medium. For CD, 15 rats completed the study at 1 month including 7 that received cell therapy and eight followed the natural evolution. All animals underwent ecocardiographic analysis at baseline and 1 month. Left ventricular, ejection fraction, end systolic, and end dyastolic volume were registered and analyzed by ANOVA. The co-culture method of SM and MSC was performed at 14 days (DMEM, with 15% FCS, 1% antibiotic, IGF-I, dexamethasone). Standard stain analysis was performed. RESULTS: For MI ejection fraction in the animals that received the co-cultured cells increased from 23.52+/-8.67 to 31.45+/-8.87 (P=.006) versus the results in the control group: 26.68+/-6.92 to 22.32+/-6.94 (P=.004). For CD, ejection fraction in animals that received the co-cultured cells increased from 31.10+/-5.78 to 53.37+/-5.84 (P<.001) versus the control group values of 36.21+/-3.70 to 38.19+/-7.03 (P=0.426). Histopathological analysis of the animals receiving co-cultured cells demonstrated the presence of myogenesis and angiogenesis. CONCLUSION: The results validated the product of SM and MSC co-cultures for treatment of diseases.

Cell transplantation: differential effects of myoblasts and mesenchymal stem cells.

BACKGROUND: Cellular transplantation has emerged as a novel therapeutic option for treatment of ventricular dysfunction. Both skeletal myoblasts (SM) and mesenchymal stem cells (MSC) have been proposed as ideal cell for this aim. The aim of this study is to compare the efficacy of these cells in improving ventricular function and to evaluate the different histological findings in a rat model of severe post-infarct ventricular dysfunction. METHODS: Myocardial infarction was induced in Wistar rats by left coronary occlusion. Animals with resulting ejection fraction (EF) lower than 40% were included. Heterologous SM were obtained by lower limb muscle biopsy and MSC by bone marrow aspiration. Nine days after infarction, rats received intramyocardial injection of SM (n=8), MSC (n=8) or culture medium, as control (n=11). Echocardiographic evaluation was performed at baseline and after 1 month. Histological evaluation was performed after HE and Gomori's trichrome staining and immunostainig against desmin, fast myosin and factor VIII. RESULTS: There was no difference in baseline EF and left ventricular end diastolic (LVEDV) and systolic volume (LVESV) between all groups. After 1 month a decrease was observed in the EF in the control group (27.0+/-7.10% to 21.46+/-5.96%, p=0.005) while the EF markedly improved in SM group (22.66+/-7.29% to 29.40+/-7.01%, p=0.04) and remained unchanged in the MSC group (23.88+/-8.44% to 23.63+/-10.28%, p=0.94). Histopathology identified new muscular fibers in the group that received SM and new vessels and endothelial cells in the MSC. CONCLUSION: Skeletal myoblasts transplantation resulted in myogenesis and improvement of ventricular function. In contrast, treatment with mesenchymal stem cells resulted in neoangiogenesis and no functional effect.

Effect of fetal growth restriction on ultrasonographically measured cardiac size.

The effect of fetal growth restriction on cardiac size is controversial. It has not been established whether cardiac size of small for gestational age (SGA) fetuses is smaller or larger than appropriate for gestational age (AGA) fetuses. Such controversy may stem from heterogeneity in study population in previous reports. Both fetal hypoxemia and increased impedance to flow in fetoplacental vessels, two findings often encountered in severe fetal growth restriction, may lead to cardiomegaly. Therefore we have measured cardiac dimensions and cardiothoracic indices in a homogeneous group of SGA fetuses without ultrasonographic or Doppler evidence of fetal distress or increased umbilical artery flow impedance (n = 10). This group was compared with AGA fetuses matched for sex and estimated fetal weight (n = 20). No differences were observed between the two groups in cardiac and chest measurements and indices. Heart circumference and area significantly correlated with fetal weight, both among AGA (r = 0.88 for both; P < 0.0001), as well as SGA fetuses (r = 0.89 and 0.88, respectively; P = 0.0006 and 0.0008).

Fetal breathing movements are associated with changes in compliance of the left ventricle.

We have tested the hypothesis that the limited fetal ventricular distensibility is not only an intrinsic cardiac characteristic but is also contributed to by the pressure exerted by the intrathoracic organs. To this purpose we have studied the diastolic cardiac function by Doppler velocimetry in 11 fetuses during fetal breathing and in 22 fetuses during apnea, controlling for gestational age at examination and heart rate. Inspiration was associated a significant increase in left ventricular compliance, as measured by deceleration time (inspiration 182.6 +/- 15.5 s vs. expiration 137.1 +/- 13.1 s vs. apnea 151.7 +/- 51.8 s), and in ventricular filling, as measured by velocity time integral (inspiration 0.086 +/- 0.020 m vs. expiration 0.064 +/- 0.014 m vs. apnea 0.065 +/- 0.011 m), compared with both the expiration and apnea groups. These increases most likely reflect changes in venous return and ventricular end-diastolic volume secondary to a decrease in intrathoracic pressure during fetal breathing.

Alterations in ventricular filling in small-for-gestational-age fetuses.

OBJECTIVE: This study was designed to evaluate if fetal diastolic cardiac function is compromised in small-for-gestational-age (SGA) fetuses with documented fetal well-being at the biophysical profile. STUDY DESIGN: We have compared indices of diastolic cardiac flow in singleton SGA fetuses with forward diastolic flow in the umbilical artery at Doppler velocimetry and documented fetal well-being (n = 10) with those of appropriate-for-gestational-age (AGA) controls with documented fetal well-being matched for gestational age at ultrasound (n = 20). RESULTS: At the mitral valve, velocity time integral (VTI) (0.059+/-0.011 vs. 0.069+/-0.011 m, p = 0.04), peak velocity of the A wave (0.426+/-0.043 vs. 0.498+/-0.087 m/s, p = 0.005), and acceleration time of the E wave (0.046+/-0.004 vs. 0.053+/-0.007 s, p = 0.008) were significantly different between SGA and AGA fetuses. At the right atrioventricular valve, only VTI was significantly different between SGA and AGA fetuses (0.065+/-0.014 vs. 0.078+/-0.011, p = 0.03). CONCLUSIONS: These findings suggest that SGA fetuses have significantly lower left and right ventricular diastolic filling compared with AGA fetuses without significant changes in diastolic function.

[Role of the atrioventricular septum and mitro-aortic separation in the pathogenesis of fixed subaortic stenosis]. / Papel do septo atrioventricular e da separação mitro-aórtica na patogênese da estenose subaórtica fixa.

PURPOSE: To analyze, by cross-sectional echocardiography, morphological features of the atrial atrioventricular and ventricular septum potentially involved in the genesis of fixed subaortic stenosis. METHODS: Forty three children with fixed subaortic stenosis were compared with 86 normal children, matched by age, sex and body surface, and 43 children with congenital heart defects without fixed subaortic stenosis. RESULTS: The groups did not differ in as age, sex or body surface. The atrioventricular septum was significantly smaller in children with subaortic stenosis than in normal children or patients with other congenital heart diseases. The ventricular septum was significantly more aligned with the atrial septum in cases than in normal children and in patients with other congenital heart diseases. The odds ratio for the development of fixed subaortic stenosis was statistically significant in the presence of a short atrioventricular septum and with alignment of the ventricular and atrial septum, when analyzed in isolation or when controlled by perimembranous ventricular septal defect. CONCLUSION: It was concluded that in fixed subaortic stenosis the atrioventricular septum length is decreased and that this alteration may be a risk factor for its development.