N-acetyl-cysteine (NAC) attenuates LPS-induced maternal and amniotic fluid oxidative stress and inflammatory responses in the preterm gestation.

OBJECTIVE: Maternal infection is associated with oxidative stress and inflammation. We sought to determine whether N-acetyl-cysteine can decrease maternal oxidative stress and the inflammatory response in preterm gestation. STUDY DESIGN: Pregnant rats 16 days, were treated with (1) lipopolysaccharide, (2) N-acetyl-cysteine 120 minutes after lipopolysaccharide, or (3) saline solution (intraperitoneal). Six hours after lipopolysaccharide administration, serum lipid peroxide formation (LPO), tumor necrosis factor-α, interleukin-6, and interleukin-1ß levels in maternal serum and amniotic fluid were determined. RESULTS: Lipopolysaccharide significantly increased maternal serum lipid peroxide formation (24-118.5 nmol/mL; P < .05), and maternal serum and amniotic fluid tumor necrosis factor-α, interleukin-6, and interleukin-1ß. N-acetyl-cysteine treatment after lipopolysaccharide significantly attenuated lipid peroxide formation (47.5 nmol/mL) and proinflammatory cytokines response in maternal serum and amniotic fluid. CONCLUSION: Maternal and amniotic fluid oxidative stress and inflammatory stimulation are attenuated by N-acetyl-cysteine even when administered after lipopolysaccharide. These results suggest that N-acetyl-cysteine may protect the fetus from adverse sequelae associated with inflammatory stimulation.

Maternal cerebral blood flow during normal pregnancy: a cross-sectional study.

OBJECTIVE: Pregnancy is associated with substantial changes in the maternal circulatory physiology. Our aim was to investigate maternal cerebral blood flow (CBF) during normal pregnancies. STUDY DESIGN: We prospectively measured maternal CBF in 210 low-risk pregnant women at different gestational ages, and in 15 nonpregnant women. CBF was assessed by measuring blood flow volume in the internal carotid artery (ICA) by dual-beam angle-independent digital Doppler ultrasound. RESULTS: ICA blood flow volume increased during pregnancy from 318 mL/min ± 40.6 mL/min in the first trimester to 382.1 mL/min ± 50.0 mL/min during the third trimester, corresponding to CBF values of 44.4 and 51.8 mL/min(-1)/100 g(-1), respectively (P < .0001). CBF changes were associated with progressive decrease in cerebral vascular resistance and moderate increase in ICA diameter. CONCLUSION: Maternal CBF is gradually increasing during normal pregnancy. Vasorelaxing impact of estrogens and other factors on cerebral vessels may explain the changes in CBF during pregnancy.

The effect of maternal hyperoxygenation on fetal circulatory system in normal growth and IUGR fetuses. What we can learn from this impact.

PURPOSE: The objectives of study were to assess and compare the effects of maternal hyperoxygenation on fetal circulation, in fetuses with intrauterine growth retardation and normal fetal growth. METHODS: Twelve singleton pregnant women with normal fetal growth and 12 singleton pregnant women with intrauterine growth restriction were recruited. Mean gestational age of 35.2 ± 3.5 and 34.7 ± 3.9 weeks, respectively. Doppler blood flow velocity waveforms were obtained from the middle cerebral artery, umbilical, main and proximal right pulmonary arteries. Pulsatility indices were calculated for all the vessels. Peak systolic velocity was determined for the middle cerebral artery. Following baseline measurements; each woman received 70% humidified oxygen for 10 min. Doppler measurements were then repeated. RESULTS: The pulsatility index in the middle cerebral artery increased significantly from 1.5 ± 0.27 to 1.88 ± 0.48, respectively (p = .006) in the high-risk group. However, it did not change significantly in the low-risk group. Hyperoxygenation caused a significant decrease in pulsatility indices in the pulmonary arteries for both groups. CONCLUSIONS: Hyperoxygenation interrupts the relative brain-sparing effect in the intrauterine growth retardation group, but it did not significantly change the pulsatility index of the middle cerebral artery in fetuses with adequate weight. The pulsatility index in the pulmonary arteries decreased significantly following hyperoxygenation.

Power spectral analysis of heart rate variability during the 100-g oral glucose tolerance test in pregnant women.

OBJECTIVE: The aims of the present study were to 1) evaluate autonomic function during the oral glucose tolerance test (OGTT) in pregnant women and 2) investigate whether gestational diabetes mellitus (GDM) modifies autonomic control of heart rate variability. RESEARCH DESIGN AND METHODS: We prospectively studied 27 pregnant women (15 without GDM, 12 with GDM) during a 100-g OGTT. The maternal electrocardiogram was recorded before and 60 min after glucose ingestion, when peak glucose levels are expected. The time and frequency domains of maternal cardiac intervals were analyzed. RESULTS: There was a significant decrease in the high-frequency (HF) band in both groups after the ingestion of glucose. The normalized low-frequency (LF) band significantly increased and the normalized HF band significantly decreased after glucose ingestion. The LF-to-HF ratio was significantly higher in the group with GDM at baseline and significantly increased in both groups after glucose ingestion. A regression analysis revealed a significant decrease in the HF band with increasing blood glucose levels. CONCLUSIONS: Acute elevation of blood glucose levels during the OGTT caused substantial autonomic alterations, including sympathetic activation and parasympathetic withdrawal. Both arms of the autonomic system were affected during the test, thus lending support to the concept that these changes are centrally integrated. The autonomic changes were less pronounced in women with GDM compared with in normal control subjects, suggesting that chronic hyperglycemia and hyperinsulinemia may alter modulation of the autonomic nervous system.

The effect of a nitric oxide donor on fetal heart rate patterns in patients with hypertension.

OBJECTIVE: To estimate whether nitric oxide donors can be administered safely to patients with pregnancy-associated hypertension based on computer analysis of antepartum fetal heart rate (FHR) tracings. METHODS: Thirty-minute recordings of FHR and fetal movements, before (stage I) and after (stage II) sublingual administration of 5 mg of isosorbide dinitrate, a nitric oxide donor, were obtained in 20 women with pregnancy-associated hypertension. RESULTS: Baseline FHR in stage I did not differ significantly from that in stage II (140.9 +/- 2.0 beats per minute and 137.5 +/- 2.1 beats per minute, respectively). There were no significant differences between stage I and II in the number (9.67 +/- 1.14 versus 9.56 +/- 1.07), amplitude (26.14 +/- 1.03 versus 24.5 +/- 0.85 beats per minute), and duration (36.03 +/- 1.46 versus 34.04 +/- 1.57 seconds) of heart rate accelerations. During stage II, the number (1.39 +/- 0.43) and duration (26.9 +/- 1.38 seconds) of heart rate decelerations did not change significantly as compared with stage I (1.67 +/- 0.33 and 26.23 +/- 1.13 seconds, respectively). However, the amplitude of heart rate decelerations was significantly higher in stage I compared with stage II (-19.36 +/- 1.44 versus -14.38 +/- 1.55 beats per minute, respectively). There were more fetal body movements during stage II than stage I (12.39 +/- 2.8 versus 9.72 +/- 2.0), but the difference was not statistically significant. CONCLUSION: Based on numeric analysis of FHR records, our data suggest that short-acting donors of nitric oxide can be administered safely to patients with pregnancy-associated hypertension.

The effect of maternal supine position on umbilical and cerebral blood flow indices.

OBJECTIVE: The brain sparing phenomenon in the fetus is a protective mechanism aimed at maintaining sufficient blood flow towards the brain during chronic or acute fetal stress, such as that caused by hypoxemia or utero-placental insufficiency. In this study we investigated whether the brain sparing effect can also be elicited by a physiological stress associated with maternal posture. Study design Twenty-three low-risk pregnant women participated in the study. Between 36 and 40 weeks' gestation, Doppler flow velocity waveforms were obtained from the fetal middle cerebral and the umbilical artery in the supine and the left lateral decubitus positions. Pulsatility index, systolic/diastolic index, and peak systolic velocities were measured and comparison was made between the left lateral and supine positions. RESULTS: The pulsatility index in the middle cerebral artery decreased from 1.78±0.27 in the left lateral decubitus position to 1.29±0.16 in supine position (p<0.0001). Peak systolic velocity decreased from 46.05±7.85cm/s to 39.43±7.95cm/s, respectively (p=0.001). The pulsatility index in the umbilical artery decreased from 0.89±0.13 in the left lateral position to 0.74±0.11 in the supine position (p<0.0001). CONCLUSIONS: This study demonstrates that the supine position in late pregnancy, causing aortic and venacaval compression, leads to brain auto-regulation that activates the brain sparing effect in the fetus. This protective mechanism, shown here for the first time to be linked to a physiological stress, may provide the basis for a novel approach in the assessment of fetal wellbeing.

Cerebral blood flow is increased during controlled ovarian stimulation.

Estrogen appears to enhance cerebral blood flow (CBF). An association between CBF and physiologically altered hormonal levels due to menstrual cycle, menopause, or exogenous manipulations such as ovariectomy or hormone replacement therapy has been demonstrated. The purpose of this study was to determine the association between ovarian stimulation and CBF in vivo by measuring blood flow in the internal carotid artery (ICA) after pituitary suppression and during controlled ovarian stimulation in women undergoing in vitro fertilization treatment cycles. ICA volume flows were measured by angle-independent dual-beam ultrasound Doppler in 12 women undergoing controlled ovarian stimulation. Measurements were performed after pituitary/ovarian suppression, in the late follicular phase, and at midluteal phase. Blood flow in the ICA increased by 22.2% and 32% in the late follicular and midluteal phases compared with the respective values obtained during ovarian suppression (P < 0.0005 and P < 0.0001, respectively). There was a significant correlation between increments in estrogen levels and increments in CBF when the late follicular phase was compared with the ovarian suppression period (r = 0.8, P < 0.001). Mean blood flow velocity significantly increased (by 15.7% and 16.9%, respectively) and cerebral vascular resistance significantly decreased (by 17.6% and 26.5%) during the late follicular and midluteal phases compared with respective measures during ovarian suppression. There was a significant correlation between an increase in estrogen levels and a decrease in cerebral vascular resistance when the late follicular phase was compared with the ovarian suppression period (r = -0.6, P < 0.05). These changes imply sex hormone-associated intracranial vasodilation leading to increased CBF during controlled ovarian stimulation.

Effect of aging on the cardiovascular regulatory systems in healthy women.

Aging, independently from the hormonal status, is a major risk factor for cardiovascular morbidity in healthy women. Therefore, we studied the effect of healthy aging on the cardiovascular homeostatic mechanisms in premenopausal and postmenopausal women with similar estrogen levels. Twelve healthy postmenopausal women, confirmed by follicular-stimulating hormone (FSH) and luteal hormone (LH) levels, were compared with 14 normally menstruating women during the early follicular phase (young-EF), to avoid as much as possible the effects of estrogen. Systolic BP was 108 +/- 1.5 vs. 123 +/- 2.5 (P < 0.001), supine norepinephrine was 260 +/- 30 vs. 216 +/- 45 and upright 640 +/- 100 vs. 395 +/- 50 pg/ml (P = 0.05) in young-EF vs. postmenopausal, respectively. Plasma renin activity and aldosterone remained unchanged. Vagal cardiac tone indices decreased significantly with aging (young-EF vs. postmenopausal): high-frequency (HF) band, root mean square successive differences (rMSSD) and proportion of R-R intervals >50 ms (PNN50%) were 620 +/- 140 vs. 270 +/- 70 (P = 0.04), 53 +/- 7 vs. 30 +/- 3 (P = 0.02), and 23 +/- 5 vs. 10 +/- 3 (P = 0.04), respectively. LF to HF ratio was 0.85 +/- 0.17 in young-EF and became 1.5 +/- 0.22 in postmenopausal (P = 0.03). Both arms of the baroreflex, +BRS (29 +/- 5 vs. 13.5 +/- 2.5, P = 0.01) and -BRS (26 +/- 4 vs. 15 +/- 1.5, P = 0.02) decreased with aging. Cardiovascular alpha(1)-adrenoreceptor responsiveness significantly increased and beta-decreased in postmenopausal compared with young EF (P < 0.001, both). The corrected QT intervals (QTc) were similar, whereas corrected JT intervals (JTc) and JTc to QTc ratio were prolonged in the postmenopausal group. We conclude that in young women, parasympathetic control is the main regulator of the cardiovascular system and in postmenopausal women, sympathetic tone dominates. The transition from parasympathetic to sympathetic control may contribute to the increased cardiovascular morbidity with aging.

The effect of isosorbide dinitrate, a donor of nitric oxide, on maternal cerebral blood flow in gestational hypertension and preeclampsia.

OBJECTIVE: The purpose of this study was to investigate the effect of a nitric oxide donor on cerebral perfusion pressure and other blood flow index values in the maternal middle cerebral and basilar arteries. STUDY DESIGN: Sublingual tablets of 5-mg isosorbide dinitrate were administered to 19 hypertensive pregnant patients. Doppler velocimetry of the middle cerebral and basilar arteries was obtained with a transcranial Doppler with the use of the transtemporal and suboccipital approach. RESULTS: The mean (+/-SEM) flow velocity in the middle cerebral artery significantly decreased from a baseline of 65.9 +/- 3.1 cm/s to 55.2 +/- 2.2 and 52.0 +/- 2.1 cm/s at 10 and 20 minutes (P <.0001). Resistance area product insignificantly increased from a baseline of 2.0 +/- 0.1 before isosorbide dinitrate to 2.19 +/- 0.11 at 20 minutes. No significant changes were observed in the resistance and pulsatility indices in the middle cerebral artery. The cerebral perfusion pressure did not change significantly after isosorbide dinitrate (84.5 +/- 7.3, 80.8 +/- 6.6, and 78.5 +/- 5.0 mm Hg at 0, 10, and 20 minutes, respectively) nor did the cerebral blood flow index. CONCLUSION: The results obtained demonstrate that cerebral perfusion pressure is unaltered by isosorbide dinitrate, despite significant changes in maternal blood pressure and in blood flow velocities in the middle cerebral artery.