Effect of fetal hypercapnia on maternal and fetal cardiovascular and respiratory function

After direct infusion of a carbonic anhydrase inhibitor to the fetus the fetal PCO2 increased to 70-80 mm Hg. Under the conditions of our sheep preparation no changes were seen in uterine or umbilical blood flows.     

Effect of alcohol on fetal cerebral function and metabolism.

The effect of maternal alcohol infusions on fetal cerebral function in terms of the electroencephalogram (EEG) and fetal brain metabolism was studied in 10 fetal sheep experiments. A 9.75 per cent alcohol-dextrose solution was infused at the rate of 15 c.c. per kilogram of maternal weight for 1 or 2 hours. Fetal cerebral uptake of oxygen was unaffected. Blood flow was significantly increased as a result of a greater decrease in resistance than decrease in blood pressure. The cerebral uptake of glucose and the glucose-oxygen utilization ratio were significantly increased. The EEG showed a decrease in amplitude and slowing of the dominant rhythm as the blood alcohol concentration increased and became isoelectric on occasion during the postinfusion period associated with a severe fetal acidosis.     

Effect of maternal cocaine administration on maternal and fetal glucose, lactate, and insulin in sheep

Although cocaine use during pregnancy is an important cause of perinatal morbidity and mortality, there are no reports of its effect on maternal and fetal carbohydrate metabolism. Six pregnant ewes and their fetuses were instrumented under halothane general anesthesia at 113-119 days' gestation. Between 124-135 days' gestation, the ewes received a single infusion of vehicle or cocaine (1.0 or 2.0 mg/kg) into the jugular vein. At least 24 hours was allowed between successive injections. Maternal and fetal blood samples were drawn at 30 and 20 minutes before and at 5, 15, 30, and 60 minutes after the injection. Both maternal and fetal glucose and lactate concentrations increased (P less than .05) after injection of cocaine at 2.0 mg/kg. There were no significant changes in maternal or fetal plasma insulin concentrations after vehicle or cocaine administration. Induction of hyperglycemia and lactacidemia could be mechanisms whereby cocaine exerts its adverse effects during pregnancy.     

Effect of alpha 1 receptor blockade upon maternal and fetal cardiovascular responses to cocaine

Previous studies in pregnant ewes have demonstrated that intravenous (IV) cocaine produces increased maternal blood pressure and vasoconstriction of the uterine arteries, resulting in decreased uterine blood flow and decreased fetal oxygen levels. To determine whether these responses to cocaine were mediated by alpha 1-adrenergic receptor stimulation, cocaine was administered to four pregnant ewes before and after phenoxybenzamine hydrochloride, an alpha 1 receptor antagonist. Before phenoxybenzamine infusion, cocaine 2.0 mg/kg produced a 53% increase in maternal mean arterial pressure (MAP), a 50% reduction in total uterine blood flow, and a 191% increase in uterine vascular resistance. Cocaine also increased fetal MAP by 24%, increased the fetal heart rate (FHR) by 51%, and reduced fetal PO2 by 29%. Alpha 1 receptor blockade after phenoxybenzamine 5.0 mg/kg was confirmed by a lack of change in uterine blood flow to IV norepinephrine 30 micrograms before cocaine administration. After phenoxybenzamine, cocaine produced no increase in maternal or fetal MAP. However, total uterine blood flow decreased 44%, uterine vascular resistance increased 59%, FHR increased 36%, and fetal PO2 fell 18%. Because the fetal responses mimicked the maternal responses to cocaine both before and after phenoxybenzamine, phenoxybenzamine apparently crossed the placenta to block fetal alpha 1 receptors as well. Alpha 1-adrenergic receptor stimulation is the major mechanism for the maternal and fetal hypertensive responses to cocaine. Although cocaine produces uterine artery vasoconstriction primarily by alpha 1 adrenergic receptor stimulation, its vasoconstrictive effects may involve other vasoactive neurotransmitters, such as dopamine or serotonin.     

卵巢切除和雌激素补充治疗对大鼠膀胱功能及结构的影响

目的通过对不同雌激素水平大鼠进行膀胱功能、组织形态和超微结构的比较,探讨雌激素对膀胱功能的影响及其作用机制。方法30只雌性成年SD大鼠均分为3组:OVX+E组(切除双侧卵巢后补充戊酸雌二醇0·8mg·kg-1·d-1,溶于0·5%羧甲基纤维素钠,每日灌胃1次)、OVX组(切除双侧卵巢)、正常对照组(未切除卵巢),后两组大鼠每日给予0·5%羧甲基纤维素钠灌胃1次。3组大鼠用药12周后行膀胱压力容积测定,并用切除膀胱的石蜡切片分析胶原纤维和平滑肌的面密度及两者比值,透射电镜下观察逼尿肌的超微结构。结果(1)OVX组膀胱最大容量(0·32±0·20)ml、顺应性(0·012±0·006)ml/cmH2O(1cmH2O=0·098kPa)和最大收缩力(1·4±0·4)cmH2O,相对于正常对照组[分别为(1·11±0·09)ml、(0·026±0·003)ml/cmH2O和(4·4±0·3)cmH2O]明显减少,差异均有统计学意义(P<0·05)。OVX+E组膀胱最大容量为(0·83±0·10)ml,相对于正常对照组减少(P<0·05),而膀胱顺应性(0·029±0·003)ml/cmH2O、最大收缩力(4·8±1·4)cmH2O与正常对照组比较,差异无统计学意义(P>0·05)。(2)胶原纤维面密度、胶原纤维面密度/平滑肌面密度比值,OVX组分别为0·218±0·041和0·54±0·08,相对于正常对照组(0·160±0·039、0·32±0·09)明显增加,差异有统计学意义(P<0·05);而OVX+E组(0·178±0·027、0·38±0·06)与正常对照组比较,差异无统计学意义(P>0·05)。(3)电镜观察OVX组逼尿肌超微结构出现退行性改变,其他两组无类似变化。结论大鼠切除双侧卵巢后膀胱功能明显降低,补充雌激素有利于改善膀胱功能,这一作用可能是通过抑制胶原增生,保护细胞器来实现的。     

The effects of ritodrine infusion on fetal myocardial function and fetal hemodynamics

The effects of ritodrine infusion on fetal myocardial function and fetal hemodynamics were studied in 18 singleton, healthy, pregnant women with premature uterine contractions. Ritodrine was given intravenously for 2 1/2 h. In 10 cases both M-mode echocardiographs of the fetal heart and measurements of the blood flow in the fetal descending thoracic aorta were made before and after the infusion. No changes took place in the functional parameters or ventricular size of the fetal heart during the infusion. Fetal heart rate increased significantly. In the aorta both the volumetric flow and time-averaged systolic peak, mean and end-diastolic velocities increased significantly, while there were no changes in wave-form indices. In 8 other cases, blood velocity waveform indices were measured by color Doppler flow mapping from the fetal middle cerebral, renal and umbilical arteries. During the infusion the waveform indices decreased significantly in the middle cerebral and renal arteries. There was no change in the indices of the umbilical artery. Ritodrine did not cause any unfavorable changes in the fetal myocardial function or blood flow in the aorta and umbilical artery. The decreased waveform indices in fetal middle cerebral and renal arteries might indicate decreased vascular resistance in these vessels.     

肾脏肾素-血管紧张素系统与胎源性肾小球硬化

肾脏肾素-血管紧张素系统(renin-angiotensin system,RAS)在肾小球硬化的发生发展中起到重要作用。近年来的研究表明,胚胎肾脏发育不良能够增加成年后肾脏疾病的易感性,且证实肾小球硬化可能具有宫内发育起源。相关研究也表明,各种因素导致的孕期不良宫内环境会分别导致胚胎期、成年后RAS出现病理性改变,进而导致胎儿肾脏发育不良、致成年后肾小球硬化易感。     

Recent cocaine use is not associated with fetal acidemia or other manifestations of intrapartum fetal distress

The objective of this paper is to evaluate the impact of recent cocaine use on umbilical cord blood gas values in cocaine-dependent pregnant women who received formal prenatal care. Ninety-two cocaine-dependent pregnant women receiving comprehensive prenatal care were divided into two groups, with patients in Group A (n = 35) testing positive for cocaine metabolites at the time of delivery and Group B (n = 57) testing negative. One hundred and three patients with no history of drug or alcohol dependence served as the control group (Group C). Umbilical cord blood gases were obtained at all deliveries. Additional variables included 1 and 5-min Apgar scores, meconium staining of the amniotic fluid, route of delivery, premature rupture of the membranes, and length of nursery stay. There were no statistically significant differences between groups in either umbilical artery pH, pO2, pCO2, bicarbonate, or base excess. Similarly, there was no difference in meconium staining of the amniotic fluid, depressed Apgar scores, cesarean delivery, or neonatal length of stay. Our data do not support an association between recent cocaine use and fetal hypoxemia or acidemia, depressed 5-min Apgar scores, meconium staining of the amniotic fluid, or cesarean delivery in cocaine-dependent pregnant women enrolled in prenatal care.     

Metabolism of cocaine by human placentas: implications for fetal exposure

To assess placental metabolism of cocaine, placentas were obtained at the time of delivery and the microsomes were extracted by ultracentrifugation within 2 hours. Placental microsomes were cultured with cocaine at physiologic plasma concentrations similar to those of cocaine users (0.75 micrograms/ml). Two control groups were established. In the first group an anticholinesterase was added to the culture to suppress enzyme activity, and in the second cocaine was cultured alone without placental microsomes to obtain baseline spontaneous conversion of the drug. The results indicate that cocaine is biotransformed by the human placenta, presumably by cholinesterase activity. This suggests that the placenta may provide a moderate degree of protection from cocaine-induced morbidity, such as abruptio placentae and fetal growth retardation, by converting cocaine into less active metabolites. These results also have pharmacogenetic implications because cholinesterase activity varies among individuals. Hence placentas that cannot transform the drug may place the conceptus at greater risk of developmental abnormalities.     

Realtime sonographic diagnosis of fetal dysplastic kidney

A case of unilateral renal dysplasia was diagnosed in utero using realtime scanning. The diagnosis was confirmed neonatally and the affected kidney was surgically removed. Pathologic findings were consistent with the features of this malformation. The echographic characteristics of renal dysplasia and the differential diagnosis are described. The potential uses of ultrasonography in the diagnosis and follow-up of pregnancies associated with or at risk of renal malformations are discussed.     

Brain damage and hypoxia in an ovine fetal chronic cocaine model.

OBJECTIVE: To assess the development of brain damage in an ovine fetal chronic cocaine model. To evaluate the effect of isolated hypoxic tests on this model and to correlate hemodynamic findings (brain-sparing effect) following fetal hypoxia and the occurrence of brain damage. STUDY DESIGN: Fifteen ewes were divided into a control group (n=7) and a cocaine treated group (n=8). From day 65 to day 134 the cocaine treated animals received a daily (5 days per week) intramuscular injection (2 mg/kg cocaine) and the control animals a placebo injection (2 ml of isotonic solution). Both groups underwent hypoxic tests (cord compression (3 min) and aortic compression (1 min)) at 90 and 134 days. In addition, anesthesia for magnetic resonance imaging (MRI) examination was carried out at 125 days. Fetal blood samples were collected during both series of hypoxic tests and the cerebral and umbilical flows were monitored by Doppler. Samples from 25 brains (control n = 10; cocaine n= 15) were processed for light and electron microscopic examination. Quantification of brain damage was done on semithin sections from six areas of cortex and germinal matrix on each fetus. RESULTS: Similar forms of brain damage (selective neuronal loss limited to the parasaggital cortex, striatum, hippocampus and Purkinje cells) was present in both groups but lesions were more frequent in the cocaine treated group as shown by quantitative analysis for the proportion of abnormal capillaries (65% vs. 35%), capillary edema (61% vs. 34%) and abnormal neurons showing delayed neuronal degeneration (DND) (66% vs. 36%) in the cocaine and control group respectively. There was no significant difference in immunoreactivity for glial fibrillary acidic protein (GFAP) but it was more marked in the cerebellum of cocaine treated animals. Fetal blood samples showed a moderate sustained hypoxia and Doppler findings demonstrated the presence of a brain sparing effect associated with increased uterine and umbilical vascular resistance in the cocaine treated group. Nevertheless, the amplitude of the heart rate increase and cerebral dilatation was significantly lower in the cocaine treated animals. CONCLUSION: This ovine fetal chronic cocaine model showed the presence of brain damage. Cocaine treatment seems to potentiate the effect of the hypoxic tests. Independent of the cause, the brain damage developed in the presence of brain sparing effect, strongly suggesting that this phenomenon is a sign of a pathological fetal condition and no guarantee that it will prevent tissue damage.