Effect of exercise on maternal hemodynamics and placental blood flow in healthy women

Intervillous placental blood flow responses to standardized exercise during late pregnancy were studied using a Xenon technique in 25 healthy women. Thirteen of them were studied twice between the 32nd and 38th weeks of pregnancy, with mean 32 (range 22 to 40) days between the studies. At the end of a 6-min exercise, mean maternal heart rate had risen from 77 +/- 10 (SD) to 154 +/- 11 beats/min, amounting to 63% of maximal oxygen uptake. Stroke volume rose by 9%, cardiac output by 65% and cardiac index by 71% as a consequence of exercise, but peripheral vascular resistance declined by 41%. The placental blood flow was at a similar level after the exercise as before the exercise, being 95 +/- 19 (mean +/- SD) ml/min/100 ml of intervillous space before, 98 +/- 24 one min after, and 93 +/- 16 30 min after the cessation of exercise. No change was found in the level of placental blood flow between the 32-34th and 37-38th weeks of pregnancy. The placental blood flow had a positive correlation with maternal weight, mean arterial blood pressure and with diastolic blood pressure. Maternal heart rate, cardiac output, cardiac index, placental weight and the birth weight of the infant was not correlated with placental blood flow. It is concluded that in normal pregnancy a short submaximal exercise has little effect on placental blood flow measured after exercise.     

Umbilical flow in the normal and pre-eclamptic placenta. A study in vitro

In order to develop a simple in vitro method for assessing adequacy of placental perfusion, umbilical flow was measured in placentae from 10 normal control women and from 10 women with pre-eclampsia, by infusing through the umbilical arteries a heparinized 0.9% saline solution. The average induced umbilical flow in placentae from uneventful pregnancies was 276 +/- 16 SE ml/min compared with 163 +/- 12 ml/min (p less than 0.001) in the pre-eclamptic group. In angiographic studies, 79 +/- 2 SE% of the cotyledons from the normal series, and only 56 +/- 3% (p less than 0.001) from the pre-eclamptic series were functional. Additionally, gross and histological examination revealed three distinct types of cotyledon. Placental areas that blanched following saline infusion showed no blood in the collapsed villi or in the intervillous space; areas distinguished by a ruddy appearance following perfusion showed blood trapped in the villi and in the intervillous space; in a third area, the findings were mixed. When compared with placental zones identified by perfusion with 5% Hypaque solution, these three anatomical regions corresponded to normal, reduced, or absent flow (blanched, intermediate, or ruddy regions, respectively). We conclude that under the conditions of this in vitro study, pre-eclamptic placentae had a greater proportion of umbilical perfusion deficits than had normal placentae.     

Fetoplacental vascular responses to prostacyclin after thromboxane-induced vasoconstriction

The vasodilator prostacyclin is produced by fetal tissues and may serve to protect umbilical blood flow. We hypothesized that prostacyclin could reverse fetoplacental vasoconstriction produced by a thromboxane mimic (U-46619). Fetal regional blood flow was measured by the radioactive microsphere technique in six unanesthetized, near-term ovine fetuses. Measurements were made in the control period, again 20 minutes after a fetal infusion of U-46619 was begun, and finally 20 minutes after prostacyclin was added to the U-46619 infusion. Mean arterial pressure rose significantly in response to U-46619 (38 +/- 1 to 51 +/- 2 mm Hg, p less than 0.01) and returned to baseline after prostacyclin (42 +/- 2 mm Hg). Renal resistance was increased from 0.16 +/- 0.01 to 0.22 +/- 0.01 mm Hg.ml-1.min.100 gm-1 (p less than 0.05) by U-46619 and decreased significantly (p less than 0.05) below baseline by addition of prostacyclin (0.10 +/- 0.02 mm Hg.ml-1.min.100 gm-1). Placental resistance also increased significantly (p less than 0.03) in response to U-46619 (from 0.15 +/- 0.01 to 0.21 +/- 0.01 mm Hg.ml-1.min.kg-1 fetal weight) but was further increased to 0.29 +/- 0.03 mm Hg.ml-1.min.kg-1 fetal weight by the addition of prostacyclin. Umbilical placental blood flow decreased significantly (p less than 0.03) when prostacyclin was added to U-46619 (315 +/- 40 to 195 +/- 30 ml.min-1.kg-1 fetal weight). Whereas U-46619 had no effect on fetal arterial blood gases, the addition of prostacyclin resulted in significant fetal acidosis (p less than 0.03). We conclude that thromboxane mimic causes fetal hypertension and renal and placental vasoconstriction. Prostacyclin reverses hypertension and renal vasoconstriction but, unexpectedly, worsens fetal placental vasoconstriction produced by thromboxane. It is likely that the observed fetal acidosis is a result of compromised placental function.     

Increased biological oxidation and reduced anti-oxidant enzyme activity in pre-eclamptic placentae

Oxidative stress occurs when cellular levels of reactive oxygen species exceed anti-oxidant capabilities and has been implicated in the pathogenesis of pre-eclampsia. In this study we have examined the tissue levels of endogenous anti-oxidant proteins (superoxide dismutase, glutathione peroxidase, thioredoxin reductase and thioredoxin) and the level of lipid and protein oxidation in placental samples from normal and pre-eclamptic pregnancies. Pre-eclamptic tissue homogenates demonstrated significantly increased levels of lipid peroxidation (20.68 +/- 7.811 microM protein versus 5.33 +/- 4.03 microM/mg protein, P < 0.001) and a trended increase in protein carbonyl concentration (248.1 +/- 97.71 units/mg protein versus 209.7 +/- 82.6 U/mg protein) when compared to controls. The levels and activities of the anti-oxidant proteins superoxide dismutase (2.48 +/- 0.6 U/mg protein versus 2.02 +/- 0.51 U/mg protein, P <0.02), thioredoxin reductase (19.25 +/- 9.81 U/mg protein versus 13.02 +/- 5.66 U/mg protein,P = 0.02), thioredoxin (107.00 +/- 18.11 ng/mg protein versus 91.12 +/- 21.18 ng/mg protein, P = 0.02) and glutathione peroxidase (17.33 +/- 6.63 mmol/min/mg protein versus 11.50 +/- 3.11 mmol/min/mg, P < 0.02) were all found to be significantly reduced when comparing pre-eclamptic placental tissue homogenates to gestational age-matched control placentae from non-pre-eclamptic pregnancies. The results of this study demonstrate a decreased enzymatic anti-oxidant capacity and increased oxidation in placental tissue from pre-eclamptic women, which may contribute to the pathogenesis of this complex disorder.     

Increase in serum concentrations of inhibin in early onset pre-eclampsia with intrauterine growth restriction

AIM: Recently, it has been hypothesized that reduced placental blood flow in early pregnancy causes changes in endothelial function, leading to pre-eclampsia. To clarify this clinically, we assessed serum concentrations of inhibin and uric acid in pre-eclamptic women compared with those of normotensive pregnant women. METHODS: One hundred and forty normotensive pregnant women (at 20-41 weeks' gestation) and 50 women with pre-eclampsia (at 24-41 weeks' gestation) were the study subjects. Pre-eclamptic women were classified according to the new criteria for pregnancy-induced hypertension produced by the Japanese Society of Obstetrics and Gynecology (JSOG). Serum concentrations of uric acid and inhibin were measured enzymatically and by radioimmunoassay, respectively. RESULTS: Serum concentrations of inhibin and uric acid in the pre-eclamptic women were significantly higher than in gestational age-matched normotensive pregnant women. There were significant correlations among inhibin and uric acid, blood pressure and birth weight. According to JSOG criteria, of the 50 pre-eclamptic women, 18 were early onset (EO), including 16 cases complicated by intrauterine growth restriction (IUGR), and 32 cases were late onset, including 12 cases complicated by IUGR. In the patients with EO and IUGR, serum concentrations of inhibin, but not uric acid, were significantly elevated as compared with those of the other pre-eclamptic women. CONCLUSION: The results suggest that an increase in the serum concentration of inhibin seen in EO pre-eclampsia, together with IUGR, might be a cause of reduced placental blood flow.     

Portal vein blood flow-effects of pregnancy, gravity, and exercise

OBJECTIVE: We sought to test the hypotheses that pregnancy increases portal vein blood flow and that regular exercise training during pregnancy limits the flow redistribution away from the splanchnic and uterine circulations in response to either gravitational or exercise-induced hemodynamic stress. STUDY DESIGN: Portal vein blood flow, which probably reflects changes in uterine blood flow, was estimated with ultrasonography in 6 regularly exercising and 6 physically active control subjects before and during pregnancy after 15 minutes of rest in the left lateral recumbent position, after 5 minutes of standing rest, and immediately and 5 minutes after 20 minutes of treadmill exercise at 55% +/- 3% of maximal aerobic capacity. RESULTS: Portal vein blood flow rose significantly during early and mid pregnancy at recumbent rest (from 660 +/- 110 to 1090 +/- 120 mL/min), standing rest (580 +/- 70 to 790 +/- 120 mL/min), immediately after exercise (160 +/- 30 to 360 +/- 60 mL/min), and at 5 minutes of recovery (520 +/- 60 to 760 +/- 110 mL/min). Before pregnancy, exercise training did not blunt the decremental effects of either gravity or exercise on portal vein blood flow. During mid and late pregnancy, exercise training had no effect on the fall in portal vein blood flow with gravitational stress, but it markedly reduced the decremental effects of exercise (average for the 2 time points, -510 +/- 80 vs -840 +/- 100 mL/min) and improved recovery at 5 minutes after exercise (940 +/- 140 vs 600 +/- 130 mL/min). CONCLUSIONS: Portal vein blood flow rises significantly during pregnancy, and flow redistribution away from the splanchnic and uterine circulations in response to severe hemodynamic stress is reduced by exercise training in mid and late pregnancy.     

Monoamine oxidase activity in the term human placenta

Using a radioenzymatic assay, placental monoamine oxidase (MAO) activity was measured at term after delivery in normal and high-risk pregnancies where decreases in placental blood flow previously were shown. MAO activity in placentas of healthy controls after spontaneous labor was similar to that after elective cesarean section not in labor (mean +/- SE, 133 +/- 18 versus 100 +/- 15 nmol/min/mg protein, respectively). Compared to controls, there was a significant reduction in placental MAO activity in high-risk pregnancies (chronic hypertension, toxemia, and diabetes mellitus), 71 +/- 14, 69 +/- 22, and 69 +/- 7, respectively (P less than 0.05). These differences also were maintained when data were expressed per total placental weight. Effects of antihypertensive drugs on MAO activity in healthy placental tissue were assessed. In homogenates, both hydralazine and magnesium sulfate reduced enzyme activity, while in explants this was not observed. The effects of certain metabolites (which are elevated in plasma of diabetic patients) on healthy homogenates also were studied. Only butyrate reduced enzyme activity. In conclusion, placental MAO activity in vitro is low in term high-risk pregnancies. This may reduce local metabolic inactivation of catecholamines and serotonin and consequently lead to a decrease in blood flow. Such a direct relationship must be confirmed in further studies.     

Placental vascular responses to nicardipine in the hypertensive ewe

Calcium channel blockers are arterial vasodilators effective in the treatment of hypertension. Therefore nicardipine, a dihydropyridine calcium channel blocker, should modulate angiotensin II-induced vasoconstriction. Regional blood flows were measured with radioactive microspheres in five chronically catheterized near-term ewes both before and 15 minutes after maternal infusion of angiotensin II at 5 micrograms/min. Nicardipine was then administered intravenously at 20 micrograms/kg/min over 2 minutes while the angiotensin II infusion was maintained. Blood flows were measured after 5 minutes. Maternal blood pressure levels were increased by angiotensin II from 83 +/- 4 mm Hg to 114 +/- 5 mm Hg, and were decreased to 70 +/- 4 mm Hg by nicardipine (p less than 0.05). Nicardipine also reversed angiotensin II-induced vasoconstriction in the renal and endomyometrial vascular beds (p less than 0.05). Unexpectedly, however, nicardipine worsened placental vasoconstriction caused by angiotensin II, as placental blood flow fell from 242 +/- 32 ml.min-1.kg-1 fetal weight to 128 +/- 7 ml.min-1.kg-1 fetal weight (p less than 0.05), and placental resistance increased from 0.48 +/- 0.04 mm Hg.ml-1.min.kg-1 fetal weight to 0.55 +/- 0.05 mm Hg.ml-1.min.kg-1 fetal weight (p less than 0.05). Nicardipine reverses angiotensin II-induced vasoconstriction systemically and in the kidney and uterus of the pregnant ewe, but does not reverse placental vasoconstriction and may significantly alter fetal cardiorespiratory status.     

The effect of maternal exercise on fetal umbilical artery waveforms

Twenty-one nulliparous women in the last trimester of pregnancy gave their informed verbal consent to undergo an acute exercise test. Fetal umbilical artery velocimetry waveforms were measured to monitor the effect of exercise on fetal umbilical artery blood flow. The mean gestational age was 32 weeks (range 28-37 weeks). The mean exercise intensity was 71% of submaximal exercise (range 67-74%). Maternal heart rate rose significantly (P less than 0.001) from a mean of 83 to 138 beats per min. Following moderate exercise, the systolic over the diastolic ratio (S/D) decreased significantly (P less than 0.001) after 2 and 20 min. This indicates a decrease in umbilical blood flow resistance and an improved placental circulation following exercise in healthy women. We conclude that maternal exercise does not appear to be harmful to the mother or her fetus at this level of exercise intensity in healthy individuals.     

Fetal infusions of plasma cause an increase in umbilical vascular resistance in sheep

Earlier studies suggested that the fetal placental circulation is relatively inert with fetal placental flow increasing or decreasing with perfusion pressure. Subsequent studies have demonstrated that the placenta may not be an unreactive vascular bed. The present study was undertaken to determine if plasma infusion-induced hypertension increased fetal placental flow in proportion to the driving pressure across the fetal placental circulation. Six fetal sheep were operated on at 118-122 days to place intravascular catheters and a flow sensor on the common umbilical artery. Starting 6 days later, the fetuses were infused with adult sheep plasma. During the 7-day-long infusion period, they received a total of 1515+/-217 (SD) ml of fluid and 93.2+/-12.0 g of protein. Fetal plasma protein concentrations increased from 34.2+/-2.3 to 77.0+/-9.7 g/l (P<0.0001). Fetal arterial blood pressures rose from 42+/-3 to 59+/-4 mmHg (P<0.01) and venous pressures rose from 2.2+/-0.5 to 4.8+/-0.8 mmHg (P<0.01). In spite of the large increase in driving pressure, fetal placental blood flow remained (statistically) constant (627+/-299 ml/min and 552+/-221 ml/min) while fetal umbilical resistance increased from 0.077+/-0.038 to 0.115+/-0.053 mmHg min/ml (P<0.01). On day 7, plasma renin activity had fallen from 6.7+/-4.2 ng/(ml/h) at preinfusion control to 0.6+/-0.6 ng/(ml/h) (P<0.05) and plasma angiotensin-II concentration had fallen from 33.2+/-26.6 to 6.2+/-3.9 pg/ml, although this fall was not statistically significant (P=0.07). Fetal placental flow did not increase with increased driving pressure across the fetal placental circulation. The increase in fetal placental resistance may be a response to the increase in arterial pressure since there was no increase in flow.     

The effect of maternal exercise on umbilical artery blood flow in insulin-dependent diabetics.

Nine insulin-dependent diabetic women underwent a moderate exercise test. The mean exercise intensity achieved was 65% (50-80%) of submaximal exercise. The maternal heart rate rose significantly after exercise from a mean of 85 b.p.m. (60-109 b.p.m.) to a mean of 140 b.p.m. (112-168 b.p.m.). Maternal systolic blood pressure rose significantly from a mean of 115 mmHg (90-130 mmHg) to a mean of 157 mmHg (145-180 mmHg). The diastolic blood pressure also rose, but insignificantly, from a mean of 71 mmHg (65-90) mmHg to a mean of 85 mmHg (80-90) mmHg after exercise. The mean umbilical pulsatility index (PI) showed significant decrease at 2 and 6 minutes of recovery from exercise and subsequently showed a significant rise after 20 minutes. This rise continued even after a full 30 minutes of recovery from exercise.     

Fetal vascular responses to prostacyclin

Prostacyclin is a potent vasodilator produced by both maternal and fetal tissues that dilates the umbilical placental vasculature in vitro. To test the hypothesis that prostacyclin dilates the fetal placental circulation in vivo, we measured blood flow by the radioactive microsphere technique in six unanesthetized near-term ovine fetuses before and during prostacyclin infusion. Fetal mean arterial pressure fell 15% from 35 +/- 3 to 31 +/- 3 mm Hg (p less than 0.05) during prostacyclin infusion, and heart rate increased from 182 +/- 6 to 208 +/- 19 beats/min (p less than 0.05). Placental blood flow changed from 240 +/- 58 to 191 +/- 46 ml.min-1.kg-1 fetal weight (p = 0.07), whereas vascular resistance was unchanged (0.16 +/- 0.04 to 0.18 +/- 0.06 mm Hg.ml-1.min.kg fetal weight). Fetal arterial pH decreased from 7.33 +/- 0.03 to 7.28 +/- 0.02 (p less than 0.05) during prostacyclin infusion, with a significant decrease in base excess from -1.2 +/- 1.4 to -3.1 +/- 1.6 (p less than 0.05) and a trend toward hypercarbia (p = 0.07). We conclude that in vivo administration of prostacyclin to the ovine fetus does not cause fetal placental vasodilation and does cause a significant fetal acidemia. The mechanism for these unexpected observations is likely shunting of blood away from the placenta to other organs in the face of systemic vasodilation.     

Characterisation of tone oscillations in placental and myometrial arteries from normal pregnancies and those complicated by pre-eclampsia and growth restriction

Agonist-induced tone oscillations (rhythmic contractions and relaxations) occur in vascular beds to allow acute regulation of volume flow and thus the delivery of oxygen and nutrients to the tissue. Mechanisms responsible for the control of human placental vasomotor tone and blood flow are poorly characterized. This study aimed to characterise thromboxane-induced tone oscillations in human placental and myometrial arteries. Chorionic plate and myometrial arteries obtained from biopsies at term were mounted for isometric tension measurement. Tone oscillations were observed in chorionic arteries only when exposed to sub-maximal (<1 microM) concentrations of U46619. Slow (mean+/-SEM) frequency (2.6+/-0.5 per hour), large amplitude (39+/-7% of peak contraction) tone oscillations were elicited by 0.03 microM U46619 (n=18). In the presence of the nitric oxide synthase (NOS) inhibitor l-NNA (100 microM) the amplitude was significantly reduced (40+/-13% to 18+/-8%, P<0.05, n=6), frequency was unaltered and the bradykinin-dependent vasodilator response was reduced (68+/-13% to 40+/-19%, P<0.05, n=6). Myometrial arteries exposed to 1 microM U46619 developed tone oscillations within 10 min, which increased in amplitude over 30min occurring at relatively constant frequency. The mean amplitude of oscillations at 30 min (31+/-7%, n=16) was similar to that in chorionic arteries but the occurrence more frequent (42.8+/-9.7 per hour, P<0.001). Inhibition of NOS did not alter tone oscillations in myometrial arteries. Tone oscillations in chorionic arteries from pre-eclamptic and growth restricted (FGR) pregnancies were reduced in amplitude whereas those in myometrial arteries had increased frequency. Inhibition of NOS further reduced oscillation amplitude in chorionic arteries from FGR pregnancies. The alterations may contribute to the vasculopathology of these conditions, or, may represent compensatory mechanisms to maintain a matching of materno-placental blood flow.     

Placental stem cell markers in pre-eclampsia

OBJECTIVE: To investigate the placental CD34, CD44, and leukemia inhibitory factor (LIF) levels in normotensive and pre-eclamptic women. METHOD: The study population consisted of 21 women with pre-eclampsia. Twenty normotensive pregnant women served as controls and were matched to pre-eclamptic patients by gestational age at delivery. Decidual samples obtained from the central part of the placenta were stored at -70 degrees C until analysis. CD44 and LIF were quantified in homogenates by enzyme-linked immunosorbent assay (ELISA), while CD34 was quantified by flow cytometry. RESULTS: The pre-eclamptic and normotensive groups were well matched. There were no significant differences in age, parity, weight, and gestational age at birth between the groups (P>0.05). The mean placental levels of CD34 (6.55+/-2.48 vs 3.16+/-1.23), CD44 (385.24+/-178.85 vs 157.75+/-31.73, and LIF (140+/-51.11 vs 96.25+/-31.62) were significantly higher in pre-eclamptic compared with normotensive women, respectively (P<0.05). CONCLUSION: Higher levels of CD34, CD44, and LIF were found in the placentas of pre-eclamptic compared with normotensive women.     

The effect of systemic infusions of dehydroisoandrosterone on the distribution of uterine blood flow in ovine pregnancy.

The effects of systemic infusions of dehydroisoandrosterone (6 mg.) on endogenous estrogen production and subsequent changes in regional blood flows and cardiac output were studied in six pregnant ewes at 105 to 128 days of gestation. Blood flows were measured with radionuclide-labeled microspheres. Plasma estrone concentrations increased from (mean +/- S.E.M.*) 27 +/- 2 to 117 +/- 13 pg. per mililiter, while estrodiol rose from 34 +/- 5 to 72 +/- 5 pg. per mililiter (p less than 0.05). Associated increases in blood flow occurred in endometrium, myometrium, and unimplanted uterine caruncles, while blood flow to the placental cotyledons was not significiantly changed. Perfusion was also increased in the Fallopian tubes, mammary gland, cervix, and vagina, the greatest fractional increase in blood flow occurring in the latter two, 387 and 456 per cent (p less than 0.005), respectively.     

The hemodynamic response of the conscious pregnant guinea pig to nicotine

The hemodynamic response to continuous intravenous infusion of nicotine, at 4.5 and 18 micrograms/min, was measured using radiolabeled microspheres in nine chronically catheterized pregnant guinea pigs. These gave serum nicotine levels of 72.3 +/- 6.6 ng/ml and 315 +/- 32 ng/ml (mean +/- SEM), respectively. During low-dose nicotine infusion there was no significant change in cardiac output, its distribution, or uteroplacental blood flow. During high-dose nicotine infusion, cardiac output fell from 257.8 +/- 30.9 ml/min to 212.7 +/- 19.3 ml/min (p less than 0.05) and uteroplacental blood flow fell from 31.2 +/- 3.1 ml/min to 22.3 +/- 2.4 ml/min (p less than 0.05). During control, low-dose, and high-dose periods, serum epinephrine levels rose from control value of 60.2 +/- 2.6 to 98.9 +/- 35 and 1200 +/- 295 pg/ml (p less than 0.05 low dose versus high dose) and serum norepinephrine levels did not change significantly during nicotine infusion. Hence at nicotine levels 20 times but not at two to five times those seen in smokers, modest reductions in cardiac output and uteroplacental blood flow were observed.     

The effect of prostacyclin on angiotensin II-induced placental vasoconstriction

Significant alterations in vascular responsiveness to angiotensin II have been documented during pregnancy. We have observed that prostacyclin, a potent vasodilating prostaglandin, does not dilate the ovine placental vasculature. However, we thought it might modulate the placental vasoconstriction produced by angiotensin II. Regional blood flows and resistances were measured by the radioactive microsphere technique in six near-term sheep. Blood flows were measured in the control condition and 15 minutes after beginning an infusion of angiotensin II at 5 micrograms/min (T1). Additional measurements were made 15 minutes after the addition of 50 micrograms/min of prostacyclin to the angiotensin II infusate (T2) and 15 minutes after withdrawing prostacyclin from the angiotensin II infusion (T3). Mean arterial pressure rose in response to angiotensin II and decreased significantly with prostacyclin administration. The renal and uterine nonplacental vascular beds showed the expected vasoconstriction in response to angiotensin II, which was then reversed to control levels by prostacyclin infusion. Unexpectedly, prostacyclin did not reverse the angiotensin II vasoconstriction in the placenta but further increased resistance (p less than 0.03). Placental resistance changed from 0.33 +/- 0.04 peripheral resistance units in the control condition to 0.42 +/- 0.06 peripheral resistance units for T1 (p less than 0.03), and prostacyclin infusion further increased placental resistance to 0.63 +/- 0.10 peripheral resistance units for T2 (p less than 0.03). We conclude that the placental vascular response to prostacyclin is different from that of other organs and that prostacyclin does not dilate, but further constricts the placenta in the near-term sheep with angiotensin II-induced systemic vasoconstriction.     

Whole-blood fibrinolytic activity in normal and hypertensive pregnancies and its relation to the placental concentration of urokinase inhibitor.

Whole-blood fibrinolytic activity was measured in 68 pregnant and 29 nonpregnant women with a sensitive, solid-state assay in which 125I-labeled fibrin was bound to polystyrene tubes. Antepartum fibrinolytic activity in 36 normotensive gravid women [234.5 +/- 29.2 (mean +/- standard error of the mean) ng fibrin lysed/30 min] was significantly (p less than 0.001) greater than that found in 28 nonpregnant normotensive women not taking oral contraceptives (63.61 +/- 7.66 ng fibrin lysed/30 min) and not different from the activity observed during the active phase of labor (198.50 +/- 16.5 ng fibrin lysed/30 min.) Normotensive pregnant patients had a significant (p less than 0.001) increase in whole-blood fibrinolytic activity (341.04 +/- 25.7 ng fibrin lysed/30 min) within the first 24 hours after delivery which persisted in measurements taken the second postpartum day. Fibrinolytic activity values before labor, in the active phase of labor, and in the first and second postpartum days in 17 patients with mild to moderate pregnancy-induced or pregd or pregnancy-aggravated hypertension were not different from those found in the normotensive group. However, patients with severe pregnancy-induced or pregnancy-aggravated hypertension had significantly (p less than 0.01) lower levels of fibrinolytic activity than normotensive patients before labor, during the active phase of labor, and on the first and second postpartum days. The placental 800 X g and 110,000 X g fractions of patients with severe hypertension had a significantly (p less than 0.001) greater capacity to inhibit "in vitro" urokinase-induced fibrinolysis than similar fractions obtained from placentas of normotensive women, and there was a significant inverse correlation (r = 0.61; p less than 0.01) between whole-blood fibrinolytic activity and urokinase inhibition by placental fractions. Our findings indicate that contrary to widely held views, fibrinolysis is extremely active in term pregnancies and during labor and that a derangement of this activity is present in cases of severe pregnancy-induced or pregnancy-aggravated hypertension.     

Insufficient efficacy of intravenous ketanserin in severe early-onset pre-eclampsia

OBJECTIVE: To analyze the efficacy of intravenous ketanserin in controlling blood pressure of severe early-onset pre-eclamptic patients. STUDY DESIGN: Pre-eclamptic patients (n=47) with a gestational age (GA) between 21 and 32 weeks were treated with intravenous ketanserin in a maximum dosage of 14 mg/h, to obtain a diastolic blood pressure of 90 mmHg or below. The number of patients reaching and maintaining target blood pressure was retrospectively assessed. Patient characteristics associated with an adequate or inadequate response to ketanserin treatment were identified. RESULTS: With a maximum intravenous dosage of ketanserin, target blood pressure was not achieved in 15 (32%) patients. A high systolic blood pressure at the start of treatment was significantly (p=0.02) associated with failure of ketanserin treatment. The median period of ketanserin treatment in the responding group was 3 days (range 1-10 days). In 26 (55%) of initially successfully treated patients, additional antihypertensive drugs had to be added to maintain adequate blood pressure control. CONCLUSION: Intravenous ketanserin lacks antihypertensive efficacy in a substantial proportion of severe pre-eclamptic patients, despite high dosages. In patients who initially respond well to ketanserin treatment, additional antihypertensive treatment is often necessary to maintain adequate blood pressure control.     

Circadian melatonin concentration rhythm is lost in pregnant women with altered blood pressure rhythm.

We assessed the correlation between the rhythm of melatonin concentration and circadian blood pressure patterns in normal and hypertensive pregnancy. Ambulatory 24-h blood pressure and blood samples every 4 h were monitored in 16 primigravidae who had shown an abnormal circadian blood pressure pattern (eight pre-eclamptic and eight normotensive) in pregnancy and 6-12 months after pregnancy. The circadian rhythm was analyzed by chronobiological measures. Eight normotensive women with maintained blood pressure rhythm served as controls. During pregnancy, melatonin concentration was significantly higher in pre-eclamptic than in normotensive women (pre-eclampsia, 29.4 +/- 1.9 pg/ml, normotensin, altered rhythm, 15.6 +/- 2.1; controls, 22.7 +/- 1.8; p < 0.001). This difference faded after pregnancy, owing to the fall observed in pre-eclampsia (11.8 +/- 3.2 pg/ml, 9.8 +/- 2.1, and 11.1 +/- 2.0, respectively; NS). The rhythm of melatonin concentration was lost in all pregnant women with loss of blood pressure rhythm. After pregnancy, normotensive women showed a reappearance of both melatonin and blood pressure rhythm, whereas pre-eclamptic women showed a reappearance of blood pressure but not melatonin rhythm. The loss of blood pressure rhythm in pregnancy is consistent with the loss of melatonin concentration rhythm. In pre-eclamptic women, the normalization of blood pressure rhythm, while melatonin rhythm remained altered, suggests a temporal or causal priority of circadian concentration of melatonin in the determination of blood pressure trend.