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Glomerular filtration and volume regulation in gravid animal models.

The gestational increase in glomerular filtration rate (GFR) that occurs in the normal rat is the result exclusively of an increase in plasma flow rate, and there is no sustained increase in glomerular capillary blood pressure during a normal pregnancy. The factor or factors that initiate the gestational renal vasodilatation (and plasma volume expansion) are maternal, not fetoplacental in origin. Apart from ruling out prostaglandins as an initiating agent, animal studies have not yet defined the precise nature of the initiating factors; it is unlikely that the gestational plasma volume expansion can be the sole cause of the increased GFR seen in pregnancy. The normal kidney in pregnancy exhibits substantial renal reserve to amino acid infusion, despite being already vasodilated by the gestational stimulus. The renal volume-sensing and control system of tubuloglomerular feedback is fully operative in pregnancy, and appears to be 'reset' to perceive the expanded plasma volume of pregnancy as normal. This observation agrees with many other indications that the sensors perceiving and controlling intravascular volume are reset during a normal pregnancy to enable the mother to accommodate the increased plasma volume without provoking a natriuretic response. Multiple pregnancies do not have any cumulative, long-term deleterious effects on renal function, either when the underlying function is normal or when it has been compromised by removal of renal mass plus high-protein feeding. In the short-term, pregnancy does not worsen kidney function when underlying glomerulonephritis is present. Therefore, the hyperfiltration of pregnancy does not appear to be a damaging entity, unlike other hyperfiltration states studied in the male rat. Still unknown is the mechanism by which pregnancy does worsen underlying glomerular disease in some women. The preliminary data in the rat, presented above, suggest that the exacerbating influence may be something other than the glomerular haemodynamic changes of pregnancy.

Animals↗

Renal tubular function in the gravid rat.

Pregnancy in the rat is accompanied by enhanced reabsorption of salt and water throughout most, if not all, of the gestational period. Many mechanisms have been suggested but definitive answers are still awaited. The major area of controversy centres around the detection of changes at term. There is general agreement that, at least in mid-gestation, the increase in reabsorption can be attributed to increases in the proximal tubules, the loop of Henle and collecting duct. The contribution of the proximal tubule to the increased reabsorption at term is still uncertain. Enhanced salt and water reabsorption is demonstrated in distal nephron segments irrespective of the stage of gestation. Micropuncture and microperfusion experiments have identified increased reabsorption of water, sodium and chloride in the loop of Henle, but it appears that there is net addition of glucose, urea and potassium to the tubular fluid in this segment which, at least for potassium and glucose, offsets to some extent increased reabsorption by the proximal tubule. Altered renal handling of other solutes (uric acid, calcium and magnesium) also occurs throughout pregnancy but the mechanisms responsible and nephron sites involved remain to be investigated. Attempts to attribute altered reabsorption to direct renal effects of changes in maternal hormones are inconclusive. Prolactin mimics some of the pregnancy-associated increases in reabsorption following chronic administration to male and non-pregnant female rats. These effects might be due to a direct renal action of the hormone or even to the volume expansion following its dipsogenic action.

Animals↗

Maternal and fetal effects of laparoscopic insufflation in the gravid baboon.

STUDY OBJECTIVE: To test the hypothesis that intraabdominal pressures (IAP) associated with abdominal insufflation for laparoscopic procedures can alter pulmonary and hemodynamic values in the pregnant baboon and hemodynamic values in the fetus. DESIGN: A descriptive physiologic study. SETTING: Animal research facility at Scott and White Memorial Hospital, Temple, TX. PARTICIPANTS: Four pregnant baboons at 120 +/- 7 days' gestation. INTERVENTIONS: The baboons underwent general anesthesia, Swan-Ganz and arterial catheter placement, and abdominal insufflation at 10 and 20 mm Hg IAP for 20-minute intervals at each pressure. The following end points were measured: maternal heart rate (MHR), mean arterial pressure (MAP), cardiac output (CO), pulmonary capillary wedge pressure (PCWP), pulmonary artery pressures (PAP), central venous pressure (CVP), systemic vascular resistance (SVR), ventilator rate (VR), oxygen saturation, and end-tidal carbon dioxide (CO2). Fetal heart rate and fetal growth values were measured, and umbilical artery Doppler flow studies were performed. MEASUREMENTS AND MAIN RESULTS: The PCWP (p <0.026), CVP (p <0.0012), and PAP (p <0.046) were significantly increased at 20 mm Hg IAP; CO decreased as IP increased. The MAP, MHR, and SVR did not change significantly with increased IAP. The only significant change in pulmonary values was the increase in peak airway pressure (p <0.001). The VR was increased from an average of 18 to 41 breaths/minute in an attempt to maintain adequate oxygen saturation and to normalize end-tidal CO2 when IAP was increased to 20 mm Hg. Respiratory acidosis (pH <7. 35, partial pressure of carbon dioxide >50 torr) was demonstrated in three of four animals within 20 minutes at an IAP of 20 mm Hg. Results of Doppler flow studies on the effects of the fetuses were unaltered immediately after this procedure compared with baseline measurements. Normal interval growth was demonstrated 2 weeks after the procedure. CONCLUSION: The baboon mothers and fetuses had no adverse effects at an IAP of 10 mm Hg, but may have significant cardiovascular and respiratory alterations associated with IAP of 20 mm Hg.

Acidosis, Respiratory↗

Life event stress and the association with spontaneous abortion in gravid women at an urban emergency department.

In this study, the authors hypothesized that life event stress is associated with an increased risk of spontaneous abortion. Using a nested case-control design in an emergency department (N = 970), stress was measured using a life event inventory and a sample drawn from R. B. Ness et al.'s (1999) Early Pregnancy Study. Gestational age at time of fetal loss served as a marker of chromosomal status. Women experiencing more than one life event used more alcohol and public assistance. Spontaneous abortion at 11 weeks or greater was associated with more life event stress (adjusted odds ratio 2.9, 95% confidence interval 1.4-6.2), whereas spontaneous abortion at any gestational age was not, implying that life event stress increases the risk of chromosomally normal spontaneous abortion. An analysis of confounders showed tobacco use was associated with an increased risk of spontaneous abortion, whereas prenatal care was only associated with fetal loss at 11 weeks or greater.

Abortion, Spontaneous↗

Intervillous blood flow in the third trimester gravid rhesus monkey (Macaca mulatta): use of sonographic contrast agent and harmonic imaging.

A properly implanted and functioning placenta is essential for the normal outcome of pregnancy. As pregnancy advances, an increasing supply of maternal blood, which reaches the intervillous space of the placenta via the spiral arteries, is necessary for continued growth and development of the fetus. Presumably, deficient blood flow to the intervillous space can lead to placental ischaemia and an unfavourable outcome, such as pre-eclampsia. In this study, we used a primate model, where echocontrast-enhanced harmonic imaging was utilized to demonstrate placental intervillous blood flow without visualization of fetal blood circulation within the chorionic villi. We propose that this technique, which requires further assessment of efficacy and safety prior to use in humans, is a potentially useful non-invasive clinical tool for assessing intervillous blood flow in the third trimester of pregnancy.

Animals↗

[Opiate addiction in gravidity - consequences for the newborn. Results of an interdisciplinary treatment concept].

AIMS: To evaluate the outcome of infants of drug dependent mothers (IDM) after establishing an interdisciplinary attention concept at the University Hospital in Vienna. To compare the influence of different maintenance agents on neonatal morbidity. PATIENTS AND METHODS: All newborns of opiate dependent mothers were prospectively included from III 1995 to IX 1999. The following data were collected: maintenance agent (methadone, slow release morphine, buprenorphine), infectious status, demographic data, congenital malformations, perinatal complications, as well as incidence and duration of the neonatal abstinence syndrome (NAS). Medical treatment with phenobarbital (1995 - 96) or morphine hydrochloride (MoHCl) (1997 - 99), respectively, was indicated when Finnegan score exceeded 10. RESULTS: 88 neonates (38 females/50 males) with a median gestational age of 39 weeks were included, 18 (20.5 %) were born prematurely. The median birthweight was 2905 g, 24 (27.3 %) infants were small for date (< 10th percentile), 15 (17 %) microcephalic. The malformation incidence was 7.4 %. 63 (72 %) of all newborns had to be treated due to abstinence syndrome: in the methadone group 76 %, in the morphine group 93 %, but in the buprenorphine group 19 % only (p < 0.01). Median duration of withdrawal was 15.1 days (d) with significant difference after antenatal buprenorphine exposure compared to methadone and morphine exposure (8.3 d versus 15 d and 16.5 d respectively). In neonates treated with phenobarbital duration of NAS was 17.6 d, whereas NAS in infants with MoHCl therapy lasted 12.8 d (p < 0.05). CONCLUSION: Incidence and duration of NAS after buprenorphine exposure was significantly lower than after methadone and morphine exposure. Withdrawal time under morphin-hydrochloride therapy was reduced by one third compared to treatment with phenobarbital.

Buprenorphine↗

Pelvic organ prolapse in the Women's Health Initiative: gravity and gravidity.

OBJECTIVE: The purpose of this study was to describe the prevalence of and correlates for pelvic organ prolapse. STUDY DESIGN: This was a cross-sectional analysis of women who enrolled in the Women's Health Initiative Hormone Replacement Therapy Clinical Trial (n = 27,342 women). Baseline questionnaires ascertained demographics and personal habits. A baseline pelvic examination assessed uterine prolapse, cystocele, and rectocele. Descriptive statistics and logistic regression models were used to investigate factors that were associated with pelvic organ prolapse. RESULTS: In the 16,616 women with a uterus, the rate of uterine prolapse was 14.2%; the rate of cystocele was 34.3%; and the rate of rectocele was 18.6%. For the 10,727 women who had undergone hysterectomy, the prevalence of cystocele was 32.9% and of rectocele was 18.3%. After controlling for age, body mass index, and other health/physical variables, African American women demonstrated the lowest risk for prolapse. Hispanic women had the highest risk for uterine prolapse. Parity and obesity were strongly associated with increased risk for uterine prolapse, cystocele, and rectocele. CONCLUSION: Pelvic organ prolapse is a common condition in older women. The risk for prolapse differs between ethnic groups, which suggests that the approaches to risk-factor modification and prevention may also differ. These data will help address the gynecologic needs of diverse populations.

Black or African American↗

Inhibitory potency of isoprenaline on guinea-pig and gravid human myometrium following extraneuronal uptake blockade.

The hypothesis that inhibitory effects of isoprenaline on myometrial contractility may be constrained by activation of putative intracellular beta-adrenoceptors negatively-coupled to adenylate cyclase was examined. Field-stimulated preparations of guinea-pig and human myometrium were used to examine the influence of the catecholamine extraneuronal uptake2 inhibitors, corticosterone and beta-oestradiol, on the inhibitory effects of the beta-adrenoceptor agonist, isoprenaline, on uterine contraction. Longitudinal and circular myometrial layers were obtained from guinea-pigs in dioestrus, primed with oestrogen before progesterone, or pregnant (Days 62-65). In the guinea-pig myometrium, corticosterone (30 microM) did not affect responses to isoprenaline. beta-oestradiol (10 microM) induced a small potentiation of the effects of isoprenaline on longitudinal myometrium from dioestrus guinea-pigs. Myometrial preparations were obtained from pregnant women (36-40 weeks gestation) undergoing caesarean section. Isoprenaline inhibited stimulation-evoked contractions in 7 of 10 preparations of the inner myometrial layer and in 5 of 8 preparations of outer myometrial layer. Corticosterone (30 microM) reduced the effects of isoprenaline on the inner layer and did not affect the outer layer. These results do not support the existence of mechanism involving isoprenaline-sensitive intracellular receptors which constrain responses to beta-adrenoceptor agonists.

Adolescent↗