Definition and treatment of severe preeclampsia.
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Diagnosis, Differential↗
Biomedical subjects
H Nisell
Publications and source records attributed to H Nisell.
The interpretation of uterine artery pulsatility index in normal and hypertensive pregnancy.
The Doppler flow velocity pulsatility index (PI) of the uteroplacental vascular bed is of debatable value for the interpretation of hemodynamic changes, when these are due both to pathological alterations in the vasculature, as in mild pre-eclampsia, and to physiological adjustments to vasoactive substances. The aim of this study was to apply a mathematical model, which includes maternal pulse pressure and mean arterial pressure, to the PI and to investigate whether this formula would add information with respect to discrimination between normal women and those with mild or severe pre-eclampsia. The subjects were patients with mild (n = 41) and severe (n = 34) pre-eclampsia and, as a control group, healthy pregnant women (n = 46). The uterine artery PI was studied by spectral Doppler analyses and compared to a P(z) value, theoretically representing a 'back pressure' in the uteroplacental circulation. Additionally, P(z) values were computed from earlier data concerning the dynamic circulatory effects of dihydralazine and acute volume expansion. The basal PI was significantly higher in the severely pre-eclamptic patients but not in the mildly pre-eclamptic patients compared to the controls. However, the P(z) was significantly higher in patients with both mild (p < 0.001) and severe pre-eclampsia (p < 0.0001) compared to the normal group. In the severely pre-eclamptic patients receiving dihydralazine, the P(z) tended to decrease (p = 0.07), in contrast to the volume-expansion group where P(z) was unaffected by the procedure. In conclusion, it seems that including measurement of the mean arterial pressure and pulse pressure with the PI adds valuable information about the circulatory status in this particular vasculature, regarding both 'basal' values and hemodynamic changes.
Journal Article↗
Hormonal, metabolic, and circulatory responses to insulin-induced hypoglycemia in pregnant and nonpregnant women with insulin-dependent diabetes.
Strict blood glucose control of pregnant women with insulin-dependent diabetes is associated with increased risk of hypoglycemia. The hormonal and circulatory responses to an acute episode of insulin-induced hypoglycemia were studied in eight pregestational and one gestational diabetic women during the last trimester of pregnancy and 8 to 12 weeks postpartum. Following an overnight fast, insulin was injected intravenously (0.1 to 0.2 IU insulin/kg). Blood samples were taken at -15, 0, 15, 30, 40, 60, 90, and 120 minutes for analyses of metabolites (glucose, nonesterified fatty acid (NEFA), glycerol, 3-hydroxybutyrate) and counterregulatory hormones (epinephrine, norepinephrine, glucagon, and cortisol). Placental scintigraphy (indium-113m) was performed in five pregnant patients before and during hypoglycemia. Both during pregnancy and postpartum, blood glucose decreased to the same low level (3.2 mmol/L) concomitantly with significant decreases in NEFA, glycerol, and 3-hydroxybutyrate. Epinephrine and norepinephrine showed significant and similar increases on both occasions in relation to hypoglycemia, although there was no response in glucagon and cortisol concentrations. Maternal heart rate was significantly higher in the pregnant compared with the nonpregnant state and increased significantly in both groups in response to hypoglycemia. Placental blood flow showed no consistent changes and was unrelated to the glucose and catecholamine responses. Fetal heart rate remained unchanged. Thus, it seems as if hormonal and circulatory responses to acute hypoglycemia are not altered in diabetic women during pregnancy.
3-Hydroxybutyric Acid↗
Effects of isradipine on endothelin-induced constriction of myometrial arteries in normotensive pregnant women.
The results of our previous studies suggested that endothelin-1 (ET-1) might be contributory to the impaired uteroplacental blood flow seen in preeclampsia. The aim of this study was to investigate the in vitro influence of isradipine on ET-1-induced contraction of myometrial resistance arteries from pregnant women, as these vessels are partly responsible for the regulation of uteroplacental blood flow in preeclampsia. Small myometrial arteries were dissected from myometrium obtained from 20 normotensive term pregnant women undergoing elective cesarean section and mounted in a tissue chamber. Tension was recorded isometrically. When ET-1 (10(-8) mol/L)-contracted vessels were exposed to increasing concentrations (10(-6), 10(-5), and 10(-4) mol/L) of isradipine, the myometrial arteries demonstrated essentially no relaxation. A significant mean relaxation of 31% was seen only with the highest isradipine concentration of 10(-3) mol/L. Pretreatment with isradipine attenuated ET-1-induced contraction by 26% at 3 x 10(-4) mol/L and by up to 80% at 10(-3) mol/L. Preincubation with lower concentrations of isradipine did not significantly reduce subsequent ET-1 contraction. The present study has thus shown that isradipine at high concentrations counteracts ET-1-induced constriction of myometrial arteries in term pregnant women. Pretreatment with isradipine at high concentrations attenuates the ET-1 contraction.
Arteries↗
Acute volume expansion in normal pregnancy and preeclampsia. Effects on plasma atrial natriuretic peptide (ANP) and cyclic guanosine monophosphate (cGMP) concentrations and feto-maternal circulation.
OBJECTIVE: To compare normal pregnancy with pregnancy-induced hypertension (PIH)/preeclampsia with respect to the effects of acute volume expansion on plasma atrial natriuretic peptide (ANP), cyclic guanosine monophosphate (cGMP) and fetal-maternal circulation. DESIGN: Observational study. SETTING: University hospital. SUBJECTS: Fifteen women with PIH/preeclampsia and 15 healthy pregnant controls. INTERVENTIONS: Before and after 30 minutes' infusion of a crystalloid solution (15 ml/kg), maternal venous blood was sampled for ANP and cGMP analysis and echocardiographic and Doppler investigations were performed. RESULTS: Basal median (range) ANP and cGMP levels were significantly higher in the PIH/preeclampsia group compared to the controls: 6.5 (3.8-30.4) compared to 3.9 (2.0-6.7) pmol/l, p < 0.01 and 5.8 (2.4-11.6) compared to 4.0 (2.3-10.8) nmol/l, p < 0.05. The response to volume load was enhanced: 4.6 (-4.5-21.8) compared to 0.7 (-4.1-8.8), p < 0.05 and 2.9 (0.1-10.9) compared to 1.2 (-5.0-6.0), p < 0.05, respectively. Systemic vascular resistance was initially higher in the patient group, 22.3 (14.1-36.7) compared to 15.6 (10.0-25.5) peripheral resistance units, p < 0.01 but the response to volume load was similar in both groups (12-13% decrease). The pulsatility index of the uterine artery, 0.85 (0.46-1.38) compared to 0.72 (0.49-1.26) and umbilical artery 0.89 (0.66-1.57) compared to 0.97 (0.74-1.31) did not differ between the groups. Volume expansion did not affect any of these variables. CONCLUSIONS: The pulsatility index of the uterine artery remained unaffected in both preeclamptic patients and healthy controls despite an increase of ANP and cGMP concentration and a systemic vasodilatation during acute volume expansion. This finding may indicate the absence of a vasodilation of the uteroplacental vascular bed.
Atrial Natriuretic Factor↗
Conservative ambulatory management of prelabor rupture of the membranes at term in nulliparous women.
OBJECTIVE: To assess maternal and fetal outcome at conservative ambulatory care of nulliparous women at term with prelabor rupture of the membranes. METHODS: A prospective study of 176 women managed conservatively in an ambulatory setting (nonstress test and assessment of amniotic fluid index every second day). RESULTS: The median rupture of the membrane to delivery interval was 30 hours. Ninety per cent were delivered within 85 hours. The patients were divided into three groups according to the time period between rupture of membranes and delivery (under the 25th, 25th-75th and above the 75th centile). The maternal infectious morbidity (0, 6, 7% respectively), fetal distress (5, 18, 17% respectively) and instrumental delivery rate (5, 16, 16% respectively) tended to be increased in the upper three quartiles, without reaching a statistically significant level as analysed by chi 2-test. Nonstress test or evaluation of amniotic fluid index was not able to predict intrapartum fetal distress. In no case was there a delay in the management of any complication due to the ambulatory care. CONCLUSION: Awaiting spontaneous labor in nulliparous women with prelabor rupture of the membranes at term does not seem to be associated with any obvious advantage. If, however, a conservative attitude is implemented, the patients can preferably be treated on an ambulatory basis.
Adult↗
Possible improvement in uteroplacental blood flow during atrial natriuretic peptide infusion in preeclampsia.
OBJECTIVE: To study the effects of low doses of the hormone atrial natriuretic peptide (ANP) on uteroplacental blood flow in patients with preeclampsia. METHODS: Eleven women with preeclampsia were infused intravenously with ANP (10 ng/kg/minute). Uteroplacental blood flow index was measured using dynamic placental scintigraphy with indium-113m. Regional blood flows were assessed by pulsed Doppler ultrasound and expressed as pulsatility index (PI). Hemodynamic measurements and blood sampling for peripheral venous plasma analysis of cyclic guanosine monophosphate (cGMP), an ANP second messenger, were performed before and after 30 minutes of infusion. Nonparametric statistics were used. RESULTS: The uteroplacental blood flow index increased by 28% (-2 to 58%; mean and 95% confidence interval). The Doppler findings were unaffected. Mean arterial blood pressure decreased from 112 (108-117) to 108 (103-114) mmHg (P < .01). Cyclic GMP increased significantly from 9.2 (6.2-12.3) to 17.4 (12.3-22.6) nmol/L (P < .01). Subjects exhibiting a substantial increase in uteroplacental blood flow index (25% or more) demonstrated a significantly greater cGMP response (P < .01) than those who did not (6% or less increase). CONCLUSION: A tendency to an increased uteroplacental blood flow index combined with minor blood pressure reduction after ANP infusion suggest the possibility of uteroplacental vasodilatation.
Adult↗
Transplacental passage of isradipine in the treatment of pregnancy-induced hypertension.
The aim of this study was to assess the concentration of isradipine in maternal and fetal plasma, and in amniotic fluid under steady-state conditions. Eight women were treated with 5-mg isradipine tablets twice daily and eight women were given slow-release isradipine capsules (SRO) twice daily for hypertension in pregnancy. Blood and amniotic fluid sampling for analysis of drug concentration was performed at delivery. In the isradipine tablet group, maternal and fetal plasma levels were 788 +/- 701 pg/mL (mean +/- SD) and 270 +/- 90 pg/mL, respectively. The corresponding levels in the SRO-treated group were 463 +/- 217 pg/mL and 185 +/- 95 pg/mL, respectively. In the amniotic fluid, the concentration was 74 +/- 42 pg/mL in the tablet group and 45 +/- 14 pg/mL in the SRO group. Therefore, isradipine passes the placental barrier, but its concentration is considerably lower in the fetal compartments.
Amniotic Fluid↗
Contractile effects of endothelin 1 and endothelin 3 on myometrium and small intramyometrial arteries of pregnant women at term.
This in vitro study was undertaken to investigate the effects of endothelin 1 (ET-1) and endothelin 3 (ET-3) on intramyometrial arteries and myometrial tissue of the uterus from pregnant women at term. Segments of small myometrial arteries (outer diameter 100-500 microns) obtained at cesarean section were isolated and mounted in tissue chambers. The effect of ET-1 and ET-3 on isometric tension was compared with the action of noradrenaline. In similar experiments on myometrial strips, the effect of ET-1 and ET-3 was studied in comparison with oxytocin. ET-1 and ET-3 both produced contractions of arteries and myometrial strips, ET-1 being the most potent. The response of ET-1 was more powerful than the effect of the reference compounds, i.e. noradrenaline with regard to myometrial arteries and oxytocin with regard to the myometrium. It is concluded that endothelins are powerful constrictors of myometrial arteries from pregnant women and possess strong oxytocic effects. In particular, ET-1 could be involved in the regulation of myometrial contractility and/or uteroplacental blood flow.
Adult↗
[Pre-eclampsia--an endothelial disease of immunologic basis?].
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Complement Activation↗
[Myoma: uterus can be saved with new therapeutic methods].
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Adult↗
Effect of isradipine on responses to standardized physical stress tests in hypertension of pregnancy.
Fourteen women with hypertension of pregnancy and who were in their last trimester were subjected to three standardized physical stress tests before and after 1-2 weeks of treatment with 5 mg of isradipine twice daily. Their blood pressure and heart rate responses to the isometric handgrip exercise, the cold pressor test, and the orthostatic tilt test were recorded. Treatment with isradipine reduced systolic and diastolic blood pressures significantly at rest. However, although the diastolic blood pressure was reduced during the stress tests, the decrease was significant only during cold pressor testing.
Blood Pressure↗
Atrial natriuretic peptide concentrations and hemodynamic effects of acute plasma volume expansion in normal pregnancy and preeclampsia.
Plasma atrial natriuretic peptide (ANP) and circulatory responses were studied during rapid plasma volume expansion with crystalloid solutions. Sixteen women with preeclampsia and 16 healthy controls in the third trimester were compared. Basal mean (+/- standard error of the mean) ANP levels were not significantly higher in the preeclamptics than in controls (13.6 +/- 3.5 versus 6.4 +/- 1.1 pmol/L; not significant), but the increment following volume expansion was more pronounced (12.9 +/- 2.6 versus 6.1 +/- 2.3 pmol/L; P less than .05). The mean plasma volume expansion was less in the preeclamptic group (6.1 +/- 0.8 versus 9.3 +/- 1.1%; P less than .05), reflecting a higher capillary permeability in this disease. Left ventricular posterior-wall thickness in diastole was increased in the preeclamptics under basal conditions as compared with the controls (9.8 +/- 0.3 versus 8.9 +/- 0.3 mm; P less than .05), as was the thickness of the interventricular septum in systole (14.3 +/- 0.5 versus 12.3 +/- 0.6 mm; P less than .05). Systemic vascular resistance was higher in the preeclamptic group (19.7 +/- 0.8 versus 15.1 +/- 1.1 peripheral resistance units; P less than .01). In the controls, cardiac output increased by 23 +/- 4% and systemic vascular resistance decreased by 17 +/- 3%. The preeclamptic women reacted in a similar way. Our results indicate that preeclampsia is associated with an enhanced ANP response despite a less pronounced increase in plasma volume during acute fluid challenge.
Adult↗
Evidence for release of endothelin-1 in pigs and humans.
The release and pharmacokinetics of endothelin-1 (ET-1) in plasma were studied in pigs and humans in vivo. Between 50-90% of plasma ET-1-like immunoreactivity (LI) was cleared by the pig and human kidney, splanchnic circulation, and skeletal muscle. The precursor big ET-1 was only cleared to a moderate extent (34%) by the kidney with progressive formation of ET-1-LI in the pig. The half-lives of circulating ET-1-LI and big ET-1-LI were about 1 and 10 min, respectively. The threshold vasoconstrictor effects for plasma ET-1-LI in the splanchnic and renal circulation in humans were around 30 pM. ET-1-LI in fetal umbilical arterial plasma was very high (15 pM before and 94 pM after establishment of breathing) compared with about 2 pM in maternal plasma. Bacterial endotoxin or sepsis increased ET-1-LI in plasma more than fivefold in both pigs and humans reaching levels close to threshold vasoconstriction. However, hemorrhagic shock or hypotension did not alter plasma ET-1-LI. It is concluded that ET-1 has a short half-life with very high regional plasma clearance, which limits detection of overflow into the systemic circulation. However, release of ET-1 reaching vasoconstrictor levels seems to occur both upon special physiological circulatory changes in the newborn and in septic shock.
Animals↗
Endothelin--a potent constrictor of small myometrial arteries of term pregnant women.
This study was performed to evaluate the in vitro effects of a new polypeptide, endothelin-1 (ET-1) on small intramyometrial vessels in comparison with the action of noradrenalin (NA). In connection with cesarean section, myometrial biopsies were obtained and small arteries (100-500 microns in diameter) were excised. Cylindrical segments of these vessels were used for registration of contractile activity after administration of ET-1 and NA. ET produced vasoconstriction and was approximately three times as powerful and 70-fold as potent as NA. It is suggested that ET may be involved in the regulation of human utero-placental blood flow.
Adult↗
Isradipine, a new calcium antagonist: effects on maternal and fetal hemodynamics.
To assess the effect of isradipine on blood pressure, and uteroplacental and fetal blood flows in pregnancy-induced hypertension, 41 women with a diastolic blood pressure greater than or equal to 95 mm Hg were included in our study. Of these, 27 received isradipine 5 mg twice daily. Uteroplacental blood flow index was calculated from the activity-time curve of the very low radiation from the placenta after intravenous injection of 18.5 MBq indium-113m. Blood flow velocity was measured in the uterine and umbilical arteries, and fetal aorta, using the pulsed Doppler technique. Investigations were performed before and after 1 week of isradipine. A control group of 14 women was examined in the same way. The isradipine group showed a significant reduction in mean arterial pressure (from 117 to 112 mm Hg) whereas there was no change in the controls. Uteroplacental blood flow indices were similar before treatment in both groups and did not change during treatment. Furthermore, the pulsatility indices were the same in both groups at the first examination and also did not change. Isradipine had no adverse effects on the fetus. In conclusion, isradipine lowered blood pressure without altering uteroplacental or fetal blood flows.
Adult↗
Endothelin, a vasoconstrictor important to the uteroplacental circulation in pre-eclampsia.
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Arm↗
Maternal and fetal levels of a novel polypeptide, endothelin: evidence for release during pregnancy and delivery.
The occurrence of endothelin (ET), a recently discovered polypeptide with potent vasoconstrictor properties, was studied in maternal and umbilical blood and amniotic fluid. The level of ET-like immunoreactivity (ET-LI) in maternal plasma was in most cases below the detection limit of the radioimunoassay, i.e. less than 2 pmol/l. The median concentration of ET-LI in the umbilical artery and vein before the initiation of breathing was 14.9 and 10.9 pmol/l, respectively. When sampling was performed after fetal breathing had begun, the arterial concentration increased to 93.7 pmol/l. Labor was not associated with increased concentrations of ET-LI, however, since neonates delivered by elective cesarean section had similar ET-LI in blood and amniotic fluid as after vaginal delivery. An approximately fivefold increase in the amniotic fluid ET-LI was seen at term as compared to early mid-trimester values. Reversed phase HPLC characterization revealed that the observed ET-LI mainly corresponded to ET-1. It is suggested that ET-1 may contribute to the fetal hemodynamic changes, e.g., closure of the umbilical vessels occurring at delivery.
Amniotic Fluid↗