Maternal treatment with alpha-phenyl-N-tert-butylnitrone attenuates secondary mitochondrial dysfunction after transient intrauterine asphyxia in the fetal rat brain.

Recirculation following 30 min of ischemia due to transient uterine artery occlusion in pregnant rats at 20 days gestation has previously been found to cause partial recovery and secondary deterioration of the cellular bioenergetic state in the fetal brain, the subsequent damage being ameliorated by a free radical spin trap agent, alpha-phenyl-N-TERT-butylnitrone (PBN). Our objective was to assess whether the secondary deterioration of the cellular bioenergetic state is due to mitochondrial dysfunction and to study whether PBN acts to prevent secondary damage to mitochondria in the fetal rat brain. Fetal neocortical tissues were sampled after 30 min of intrauterine ischemia and after 1, 2 or 4 h of recirculation. PBN or vehicle was given 1 h after recirculation. Homogenates were prepared, and ADP-stimulated, nonstimulated and uncoupled respiratory rates were measured polarographically. Ischemia was associated with a decrease in ADP-stimulated and uncoupled respiratory rates, with a marked fall in the respiratory control ratio, defined as ADP-stimulated divided by nonstimulated respiration (p < 0.01). Recirculation (1 h) brought about partial recovery, but continued reflow (2 and 4 h) was associated with a secondary deterioration of respiratory functions (p < 0.01). The secondary deterioration was prevented by PBN (p < 0.05). The results demonstrate that the secondary deterioration of the cellular bioenergetic state in ischemia-reperfusion is due to secondary mitochondrial dysfunction and that this deterioration may be induced by oxygen-derived free radicals in the immature fetal brain.

[Management of regular exercise in pregnant women].

In recent years with ever-increasing numbers of pregnant women wanting to participate in sport activities, the question as to how safe maternal exercise is for mother and fetus has become more important. The effects of pregnancy on maternal cardio-respiratory system include increases in oxygen consumption, cardiac output, heart rate, stroke volume, and plasma volume. The increase in oxygen reserve seen in early pregnancy is reduced later, suggesting that maternal exercise may present a greater physiological stress in the third trimester. The aims of this article are 1) to comment on the evidence relating to the health risks and benefits of physical activity for pregnant women and their unborn fetuses and 2) to realize guidelines for management of maternal exercise. In the absence of either obstetric or medical complications, pregnant women can continue to exercise and derive related benefits. The type, intensity, frequency, and duration of the exercise seem to be important determinants of its beneficial effects. Evidence suggests that weight-bearing exercise produces a greater decrease in oxygen reserve than non weight-bearing exercise. Furthermore, to maintain a heart rate below 150 beats per minute during pregnancy, the intensity of weight-bearing exercise must be reduced. In addition, depending on the individual's needs and the physiologic changes associated with pregnancy, women may have to modify their specific exercise regimens. Although increases in the frequency of uterine contractions have been observed during physical activities, changes are often minimal. In response to moderate exercise, the increase in frequency of uterine contractions is gestation dependent and significant in the third but not in the second trimester. The physiological adaptations to exercise during pregnancy appear to protect the fetus from potential harm and, while an upper level of safe activity has not been established, the benefits of continuing to be active during pregnancy appear to outweigh any potential risks. All decisions about participation in physical activity during pregnancy should however be made by women in consultation with their medical advisers.

Vitamins ameliorate secondary mitochondrial failure in neonatal rat brain.

Recirculation after transient intrauterine ischemia has previously been found to be accompanied by secondary mitochondrial dysfunction in the immature rat brain. This study was performed to assess the efficacy of combined treatment with ascorbic acid and alpha-tocopherol in improving secondary brain damage. On the 17th day of gestation, transient intrauterine ischemia was induced by 30 minutes of uterine artery occlusion. Either vehicle, ascorbic acid, alpha-tocopherol, or combination of ascorbic acid and alpha-tocopherol was randomly administered to pregnant rats before and after occlusion. The pups were delivered by cesarean section at 21 days of gestation, and cerebral neocortical tissue was sampled. The mitochondrial respiration was measured polarographically in homogenates. In the ischemia uterine horn, mitochondrial activity of the vehicle treatment decreased significantly to 56% of nonischemic controls. Treatment with ascorbic acid or alpha-tocopherol alone demonstrated a moderate improvement of the secondary mitochondrial dysfunction to 64% and 62% of nonischemic controls, respectively. The combined treatment caused a normalization of mitochondrial activity to 91% of nonischemic controls. These results indicate that combined treatment with ascorbic acid and alpha-tocopherol has a more protective effect against secondary mitochondrial dysfunction after transient intrauterine ischemia compared with the administration of ascorbic acid or alpha-tocopherol alone.

Assessment of endometrial perfusion with Doppler ultrasound in spontaneous and stimulated menstrual cycles.

OBJECTIVE: Endometrial perfusions were measured by Doppler ultrasound to evaluate the influence of spontaneous menstrual cycles and to study the effect of clomiphene citrate. METHODS: Flow waveforms in right and left uterine arteries were obtained by using transvaginal color Doppler ultrasonography in infertile women with 60 spontaneous menstrual cycles and 37 clomiphene citrate stimulated cycles from the follicular to the luteal phase. RESULTS: In the spontaneous menstrual cycles, the uterine arterial blood flow increased significantly from the follicular phase to the day of ovulation and then increased markedly to about 200 approximately 230% of the follicular phase after the 6th day of ovulation. In the clomiphene citrate stimulated cycles, the uterine arterial blood flow did not change during the periovulatory period and then increased significantly to about 180 approximately 220% of the follicular phase after the 6th day of ovulation. CONCLUSIONS: In the present study, the clomiphene citrate stimulated cycles showed lower endometrial perfusion during the periovulatory period compared with those in the spontaneous menstrual cycles. The results suggest that the assessment of endometrial perfusion with Doppler ultrasound can be used to reveal unexplained infertility problems in induced ovarian cycles.

Short therapeutic window for nifedipine in transient intrauterine ischemia in fetal rat brain.

The aim of this study was to explore whether nifedipine influences the secondary deterioration of cerebral mitochondrial function after transient intrauterine ischemia in fetal rats. Intrauterine ischemia was induced by a 30-min occlusion of the right uterine artery at 20 days of gestation in Wistar rats. Nifedipine (1 mg kg(-1)) or vehicle was injected subcutaneously before the onset of ischemia or 1 h after the start of recirculation. Fetuses were delivered by cesarean section at the end of ischemia (n=6 with vehicle; n=6 with nifedipine pretreatment) or at 4 h of recirculation (n=6 with vehicle; n=6 with nifedipine pretreatment; n=6 with nifedipine posttreatment), and the cerebral mitochondrial respiration was measured polarographically. Tissue oxygen tension was evaluated in placental and fetal cerebral tissues (n=5 with vehicle; n=5 with nifedipine pretreatment). The vehicle treated animals showed a significant decrease in mitochondrial activities at the end of ischemia and 4 h of recirculation. Nifedipine attenuates the secondary deterioration at 4 h of recirculation when given just prior to ischemia, but had no neuroprotective activity when given 1 h after the start of recirculation. Nifedipine pretreatment had no influence on oxygen delivery in placenta and fetal cerebrum during and after ischemia. Despite the short therapeutic window, the treatment of nifedipine attenuates the secondary deterioration of cerebral mitochondrial function after transient intrauterine ischemia in fetal rats when given just prior to ischemia.

Effect of dexamethasone on mitochondrial maturation in the fetal rat brain.

OBJECTIVE: The objective of the present study was to explore whether prenatal dexamethasone treatment influences mitochondrial maturation in the fetal rat brain. STUDY DESIGN: Mitochondrial respiration was measured polarographically with homogenates of fetal cerebral cortical tissues on day 16 (with saline solution, n = 8; with dexamethasone, n = 8), day 18 (with saline solution, n = 8; with dexamethasone, n = 8), and day 20 (with saline solution, n = 8; with dexamethasone,n = 8) of gestation. Four doses of dexamethasone (0.1 mg small middle dot kg) or vehicle (saline solution) were given, with an interval of 12 hours, until 12 hours before each measurement. RESULTS: In the vehicle-treated animals, mitochondrial respiratory activity was increased significantly after day 18 of gestation. Dexamethasone-treated animals showed a significant increase in mitochondrial activity at day 16 of gestation compared with vehicle-treated animals. CONCLUSION: The results indicate that prenatal dexamethasone treatment contributes to the precocious maturation of mitochondrial activity in the fetal rat brain. Because acceleration in cerebral mitochondrial activities is required immediately after birth to maintain high-energy phosphate levels, the precocious maturation may be crucial for the successful outcome of the preterm infant.

Windows of therapeutic opportunity on fetal growth retardation induced by transient intrauterine ischemia in rats.

OBJECTIVE: To assess the windows of therapeutic opportunity for drugs with various chemical actions on fetal growth retardation induced by transient intrauterine ischemia in rats. METHODS: At 17 days of gestation, ischemia was induced by 30 min of right uterine artery occlusion. The administration of either alpha-phenyl-N-tert-butyl-nitrone (PBN), FK 506, nifedipine, or MK-801 to pregnant rats was randomly started before occlusion, 1 hour, 3 hours, or 24 hours after recirculation. All of the pups were delivered by cesarean section at 21 days of gestation and were weighed to determine the degree of fetal growth retardation. RESULTS: The vehicle-treated animals exposed to ischemia showed a significant decrease in fetal body weight compared with the normoxic control animals. The growth disturbances were prevented by nifedipine and MK-801 only when given just prior to ischemia. In contrast, PBN and FK 506 had a protective effect even when given 1 hour and 3 hours after the start of recirculation, respectively. CONCLUSIONS: The present results indicate that treatment with PBN and FK 506 gives relatively wide windows of therapeutic opportunity in fetal growth retardation induced by transient intrauterine ischemia in rats and suggest the possibility of therapeutic intervention after the start of recirculation.

Effect of regular maternal exercise on lipid peroxidation levels and antioxidant enzymatic activities before and after delivery.

This study was designed to investigate the influence of maternal aerobic exercise on lipid peroxidation levels and antioxidant enzymatic activities before and after delivery. Predelivery and 1- and 24-hour post partum blood samples were collected from 18 nulliparous healthy pregnant women who exercised regularly throughout the whole period of pregnancy and from 22 matched controls. The plasma concentration of malondialdehyde (MDA) was measured as an indicator of lipid peroxidation. Erythrocyte enzymes, superoxide dismutase (SOD), glutathione peroxidase (GSHPx) and catalase (CAT), were measured as intracellular antioxidant markers. In the control group, MDA increased slightly from predelivery to 1 hour post partum and then increased significantly at 24 hours post partum, with significant increase in SOD and CAT activities. On the other hand, MDA of the exercise group remained unaltered at 1 and 24 hours after delivery. At 1 hour post partum, the SOD and CAT levels of the exercise group increased markedly and then decreased to predelivery levels. The present results indicate that uncontrolled lipid peroxidation occurs during labor and suggest that continuing regular maternal exercise may reduce labor-induced lipid peroxidation by improving the defense capabilities against free radical generation.

Doppler ultrasound measurement of cerebral blood flow in healthy pregnant women.

PURPOSE: To compare global cerebral blood supply in healthy pregnant women and nonpregnant women. MATERIALS AND METHODS: Flow volumes in the common, internal, and external carotid, arteries and the vertebral arteries were determined using color Doppler ultrasonography in 17 nonpregnant women, 55 healthy pregnant women at 10 to 40 weeks gestation, and 24 puerperal women within 1 week after spontaneous delivery. Global cerebral blood flow was defined as the sum of flow volumes in the bilateral internal carotid and vertebral arteries. RESULTS: In the nonpregnant group, mean flow volumes of the common, internal, and external carotid arteries and the vertebral arteries, and mean global cerebral blood flow volume were (mean±SD) 863±108 ml/min, 554 ±94 ml/min, 386±65 ml/min, 115±24 ml/min, and 669±104 ml/min, respectively. During the second trimester, flow volumes of the common and external carotid arteries increased significantly in the healthy pregnant women, to about 130 percent and 140 percent of the nonpregnant level, respectively. Global cerebral blood flow volume remained unchanged during pregnancy. CONCLUSION: During pregnancy, increase in flow volumes in the common carotid arteries were accompanied by elevated flow volumes of the external carotid arteries but not the internal carotid arteries. This distribution would tend to regulate the volume of global cerebral blood flow throughout the period of pregnancy.