Nitric oxide and reactive species are modulated in the polyphenol-induced ductus arteriosus constriction in pregnant sheep.

OBJECTIVE: Because we have previously demonstrated the relation between polyphenol-rich foods (PRF) consumption and ductus arteriosus constriction, in this work, pregnant sheep were submitted to oral PRF intake for 14 days to understand how this process occurs. Fetal Doppler echocardiography, oxidative and inflammatory biomarkers and total polyphenol excretion were evaluated. RESULTS: The high polyphenol intake induced ductus arteriosus constriction by 71.6% increase in systolic (P = 0.001) and 57.8% in diastolic velocities (P = 0.002), and 18.9% decrease in pulsatility index (P = 0.033), along with 1.7-fold increase in total polyphenol excretion, 2.3-fold decrease in inflammatory mediator nitric oxide and following redox status changes (mean ± standard deviation): higher protein carbonyls (1.09 ± 0.09 and 1.49 ± 0.31), catalase (0.69 ± 0.39 and 1.44 ± 0.33) and glutathione peroxidase (37.23 ± 11.19 and 62.96 ± 15.03) in addition to lower lipid damage (17.22 ± 2.05 and 12.53 ± 2.11) and nonprotein thiols (0.11 ± 0.04 and 0.04 ± 0.01) found before and after treatment, respectively. Ductal parameters correlated to NOx , catalase, glutathione peroxidase and protein carbonyl. CONCLUSION: Our results highlight the need to reduce maternal PRF intake in late pregnancy to prevent fetal duct constriction through NO-mediated vasoconstrictive action of polyphenols.

Fetal ductal constriction caused by maternal ingestion of green tea in late pregnancy: an experimental study.

OBJECTIVES: The aim of this study was to test the hypothesis that experimental maternal intake of green tea in late pregnancy causes fetal ductus arteriosus constriction, probably because of prostaglandin inhibition. METHODS AND RESULTS: Twelve fetal lambs (pregnancy > 120 days) were assessed before and after maternal administration of green tea (n = 8) or water (n = 4; controls) as the only source of liquid. After 1 week, echocardiography showed signs of constriction of the ductus arteriosus in all fetuses from mothers ingesting green tea, with increase in mean systolic velocity(from 0.70 ± 0.19 m/s to 0.92 ± 0.15 m/s, 31.4%, p = 0.001) and mean diastolic velocity (0.19 ± 0.05 m/s to 0.31 ± 0.01 m/s, 63.1%, p < 0.001), decrease of pulsatility index (2.2 ± 0.4 to 1.8 ± 0.3, 22.2%, p = 0.003) and increase of mean right ventricular/left ventricular diameter ratio (0.89 ± 0.14 to 1.43 ± 0.23, 60.6%, p < 0.001). In the four control fetuses, there were no significant changes. All lambs exposed to green tea also showed at autopsy dilated and hypertrophic right ventricles, which was not present in control fetuses. Histological analysis showed a significantly larger mean thickness of the medial avascular zone of the ductus arteriosus in fetuses exposed to green tea than in controls (747.6 ± 214.6 µm vs 255.3 ± 97.9 µm, p < 0.001). CONCLUSIONS: This study in fetal lambs shows a cause and effect relationship between experimental maternal exposure of green tea and fetal ductus arteriosus constriction in late pregnancy.

Dynamics of the septum primum in fetuses with intrauterine growth restriction.

PURPOSE: To test the hypothesis that the linear displacement of the septum primum (SP) is lower in fetuses with intrauterine growth restriction (IUGR) than in fetuses with appropriate growth for gestational age (AGA). METHODS: In a cross-sectional study, the ratio between the SP displacement and left atrial diameter (excursion index [EI]) was compared in 27 fetuses with IUGR (group 1), 24 fetuses with AGA of hypertensive mothers (group 2), and 35 controls (group 3). Flow through the atrioventricular (AV) valves and the umbilical artery resistance index (RI) were also compared. RESULTS: Irrespective of gestational age, mean EI in group 1 (0.41 +/- 0.07) was significantly lower than in group 2 (0.48 +/- 0.07; p < 0.001) and than in group 3 (0.50 +/- 0.06; p < 0.001), with no significant differences between groups 2 and 3. In fetuses over 30 weeks of gestation of group 1, EI was lower (0.38 +/- 0.05) than in group 2 (0.49 +/- 0.07) and group 3 (0.51 +/- 0.06; p < 0.001). There was significant inverse correlation between EI and RI (r = 0.46; p < 0.01) and no correlation between EI and AV flow velocities. CONCLUSIONS: SP mobility is reduced in fetuses over 30 weeks with IUGR compared with AGA fetuses. These findings may depend on alterations of left ventricular diastolic function and are correlated to the degree of placental insufficiency.

Assessment of diastolic ventricular function in fetuses of diabetic mothers using tissue Doppler.

OBJECTIVE: To identify the presence of ventricular diastolic dysfunction by tissue Doppler in fetuses of diabetic mothers, with or without septal hypertrophy, in comparison to fetuses of nondiabetic mothers. METHODS: A contemporary transverse study in fetuses with a gestational age between 25 weeks to term, studying diastolic function by assessment using tissue Doppler and pulsed wave Doppler of the atrioventricular diastolic flow. The mothers of the fetuses all had previous or gestational diabetes, and were referred to the Fetal Cardiology Unit of the Institute of Cardiology in Porto Alegre, Brazil. We analysed variance with the Student-Neumann-Keuls post hoc test. An alfa of 0.05 was considered significant for statistical analysis. RESULTS: The mean myocardial velocities of the E'and A' waves at the mural mitral annulus, in fetuses of diabetic mothers with myocardial hypertrophy, were, respectively, 7.00 plus or minus 1.6 centimetres per second, and 10.24 plus or minus 3.3 centimetres per second. In the fetuses of diabetic mothers group without myocardial hypertrophy, the comparable values were 7.19 plus or minus 2.4 centimetres per second and 10.77 plus or minus 3.77 centimetres per second, respectively. In the control group, they were 4.81 plus or minus 0.85 centimetres per second and 8.01 plus or minus 2.2 centimetres per second. The difference between the velocities in fetuses of diabetic mothers and in fetal normal mothers was statistically significant (p less than 0.05). Statistically significant differences were also observed in E' and A' diastolic waves at the aortic mitral annulus, as well as for the tricuspid annulus when tissue Doppler assessment was carried out in the same sample. The mean ratio between the E and E' of mitral and tricuspid waves in the control fetuses of normal mothers was significantly higher than in fetuses of diabetic mothers. CONCLUSION: Pulsed tissue Doppler, when used in fetuses of diabetic mothers and compared with fetuses of nondiabetic mothers, shows evidence of impaired diastolic function, independently of the presence of myocardial hypertrophy.

Ductus venosus flow and myocardial hypertrophy in fetuses of diabetic mothers.

OBJECTIVE: To test the hypothesis that the pulsatility index of ductus venosus (PIDV) is greater in the fetuses of diabetic mothers (FDM) with myocardial hypertrophy (MH) than in the FDM with no MH and in the control fetuses of nondiabetic mothers (FNDM). Comparing the results with mitral and tricuspid diastolic peak flows. METHODS: The cross-sectional study included fetuses with gestational ages ranging from 20 weeks to term, divided into the following 3 groups: 56 FDM with MH (group I), 36 FDM with no MH (group II), and 53 FNDM (group III, control). The Doppler echocardiogram assessed the PIDV through the ratio (systolic velocity - presystolic velocity)/mean velocity. The mitral and tricuspid E and A waves were also assessed. RESULTS: The mean PIDV in groups I, II, and III were 1.13 +/- 0.64, 0.84 +/- 0.38, and 0.61 +/- 0.17, respectively. Using ANOVA and the Tukey test, a statistically significant difference was found in the 3 groups (P = 0.015 between groups I and II; P < 0.001 between groups I and III; and P = 0.017 between groups II and III). The mean mitral E wave was significantly greater in group I (0.39 +/- 0.12 m/s) than in groups II (0.32 +/- 0.08 m/s) (P = 0.024) and III (0.32 +/- 0.08 m/s) (P = 0.023). The mean tricuspid E wave was also greater in group I (0.43 +/- 0.1 m/s) than in group III (0.35 +/- 0.10 m/s) (P = 0.031). CONCLUSION: The PIDV is significantly greater in FDM with MH than in FDM with no MH and in FNDM. Because the PIDV may represent modifications in ventricular compliance, this index may be a more sensitive parameter for assessing fetal diastolic function.

Study of global left atrial shortening in fetuses of diabetic mothers.

OBJECTIVE: To test the hypothesis that left atrial shortening fraction is lower in fetuses of diabetic mothers than in fetuses of mothers with no systemic disease. METHODS: Forty-two fetuses of mothers with previous diabetes or gestational diabetes and 39 healthy fetuses of mothers with no systemic disease (controls) underwent echocardiographic examination. Their gestational ages ranged from 25 weeks to term. The left atrial shortening fraction was obtained with the following formula: (left atrial maximum diameter - left atrial minimum diameter)/left atrial maximum diameter. Data were compared using the Student t test, with an alpha level of 0.05. RESULTS: Mean left atrial shortening fractions in fetuses of diabetic mothers and in those in the control group were 0.39 +/- 0.15 and 0.51 +/- 0.11, respectively. This difference was significant with P < 0.001. CONCLUSION: Left atrial dynamics, with a reduction in global left atrial shortening, is increased in fetuses of diabetic mothers. We speculate that this parameter may be useful in assessing fetal left ventricular diastolic function.

Pulmonary vein pulsatility in fetuses of diabetic mothers: prenatal Doppler echocardiographic study.

OBJECTIVE: To verify the hypothesis that the pulmonary vein pulsatility index is higher in fetuses of diabetic mothers than it is in normal fetuses of nondiabetic mothers. METHODS: Twenty-four fetuses of mothers with either gestational or previous diabetes (cases), and 25 normal fetuses of mothers without systemic disease (control) were examined. Fetuses were examined through prenatal Doppler and color flow mapping. The pulmonary vein pulsatility index was obtained by placing the pulsed Doppler sample volume over the right superior pulmonary vein and applying the formula (systolic velocity - presystolic velocity)/mean velocity. RESULTS: The mean gestational age of the study fetuses was 30.3 2.7 weeks, and gestational age of the controls was 29 3.3 weeks, with no significant difference in gestational age between groups (p=0.14). Fetuses of diabetic mothers had a mean pulmonary vein pulsatility index of 1.6 1, and those of the control group had an index of 0.86 0.27. CONCLUSION: Fetuses of diabetic mothers had pulmonary vein pulsatility indexes (parameter easily obtained through Doppler echocardiography that may be related to fetal diastolic function) higher than those in fetuses of mothers with normal glycemia.