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H Nisell

Publications and source records attributed to H Nisell.

At least 37 records · Page 2Linked to original sources

Preeclampsia may cause both overperfusion and underperfusion of the brain: a cerebral perfusion based model.

BACKGROUND: The hypothesis was that low cerebral perfusion pressure is more common in women with mild preeclampsia as compared to those with severe preeclampsia, while high cerebral perfusion pressure is more common in women with severe preeclampsia than in women with mild preeclampsia. DESIGN: Prospective, observational study. SETTING: University teaching hospitals. METHODS: Transcranial Doppler ultrasound was used to measure the blood velocity in the middle cerebral arteries of 54 patients with mild preeclampsia and 44 patients with severe preeclampsia. Blood pressure was measured simultaneously. Cerebral perfusion pressure was calculated and plotted on the same axes as data from 63 normal pregnant women. Data outside of the 95% prediction limits were regarded as abnormal. All studies were prior to labor, and before volume expansion or treatment. ANALYSIS: Student's t-test, Mann Whitney U test, and Fisher's exact test as appropriate with two-tailed p<0.05. MAIN OUTCOME MEASURE: The number of patients in each group with cerebral perfusion pressure values outside the normal 95% prediction limits. RESULTS: Almost the same number of women with mild (21/54=39%) and severe (15/44=34%) preeclampsia had measurements within the normal range (p=0.78). Mild preeclamptic women were more likely to have low (28/54=52%) rather than high cerebral perfusion pressure (p<0.001), while severe preeclamptics were more likely to have high cerebral perfusion pressure (26/44=59%) than low (p<0.001). CONCLUSIONS: In preeclampsia the brain can be normally perfused, underperfused and over-perfused. Although many women with mild preeclampsia will have underperfusion (52%), and a significant number of women with severe preeclampsia will have overperfusion (59%), many preeclamptic women have cerebral perfusion within the normal range.

Adult↗

Fetal and neonatal mortality in the postterm pregnancy: the impact of gestational age and fetal growth restriction.

OBJECTIVE: Our purpose was to examine the impact of gestational age and fetal growth restriction on fetal and neonatal mortality rates in the postterm pregnancy. STUDY DESIGN: All deliveries occurring in Sweden between Jan. 1, 1987, and Dec. 31, 1992, were evaluated for participation in this study. Data were derived from the National Swedish Medical Birth Registry. Pregnancies were selected for inclusion in the study on the basis of the following criteria: (1) singleton pregnancy, (2) reliable dates, (3) gestational age > or = 40 weeks, and (4) maternal age 15 to 44 years. Fetal growth restriction was defined as birth weight <2 SD below the mean for gestational age. A total of 181,524 pregnancies met the inclusion criteria and formed the study population. Fetal and neonatal mortalities at 40 weeks' gestation were used as reference levels. Logistic regression analysis was used to estimate the independent effects of gestational age and fetal growth restriction on fetal and neonatal mortality rates. RESULTS: A significant rise in the odds ratio for fetal death was detected from 41 weeks' gestation and on (odds ratios 1.5, 1.8, and 2.9 at 41, 42, and 43 weeks, respectively). Odds ratios for neonatal mortality did not demonstrate a significant gestational age dependency. Fetal growth restriction was associated with significantly higher odds ratios for both fetal and neonatal mortality rates at every gestational age examined (with odds ratios ranging from 7.1 to 10.0 for fetal death and from 3.4 to 9.4 for neonatal death). CONCLUSIONS: Postterm pregnancies have long been considered to be at high risk for adverse perinatal outcome. This study documents a small but significant increase in fetal mortality in accurately dated pregnancies that extend beyond 41 weeks of gestation. This study also demonstrates that fetal growth restriction is independently associated with increased perinatal mortality in these pregnancies.

Adolescent↗

Altered mRNA expression pattern of placental epidermal growth factor receptor (EGFR) in pregnancies complicated by preeclampsia and/or intrauterine growth retardation.

Placental pathology in preeclampsia (PE) and intrauterine growth retardation (IUGR) is associated with alterations of the placental epidermal growth factor receptor (EGFR). It is encoded by a single gene, which gives rise to two different full-length transcripts and one putative truncated transcript in the placenta. The aim was to investigate if the placental mRNA expression pattern of EGFR differs between women with PE and/or IUGR and normal pregnancies. Tissue samples from placentas were obtained immediately after delivery. Total nucleic acids were prepared and mRNA levels of EGFR transcripts were measured by a solution hybridization technique. In the group with IUGR the placental mRNA expression of the two full-length transcripts was found to be significantly lower than in placentas from normal pregnancy, whereas the expression of the truncated transcript was higher. The groups with PE or PE with IUGR had a significantly higher mRNA expression of the truncated transcript, while there were no significant differences in the mRNA expression of the two full-length transcripts. These findings are consistent with an important role for EGFR in the regulation of placental and fetal growth.

Biopsy↗

Placental expression of endothelial constitutive nitric oxide synthase mRNA in pregnancy complicated by preeclampsia.

BACKGROUND: The role of nitric oxide (NO) in normal pregnancy and pregnancy complicated with preeclampsia (PE) and/or intrauterine growth restriction (IUGR) still remains questionable. The placenta lacks autonomic innervation, therefore blood flow must be regulated by humoral and endothelium derived factors. NO is a potent vasodilator released by endothelial cells. It is synthesized by the catalytic action of the endothelial constitutive nitric oxide synthase (ecNOS). Moreover, the synthesis of NO in normal human placental vasculature has already been established and impairment of the uteroplacental blood flow in pregnancies complicated by PE and/or IUGR has been demonstrated. DESIGN AND METHODS: The aim of the present study was to compare the expression of ecNOS mRNA in placenta from women with complicated and normal pregnancies. Placenta was collected from women with PE (n = 13) or small for gestational age (SGA) (n = 8), both PE and SGA (n = 7) and normal pregnancies (n = 41). Total nucleic acids were prepared and a solution hybridization technique was used for mRNA analysis. RESULT: The mRNA expression of ecNOS was significantly higher (p<0.05) in all groups of complicated pregnancies compared to normal pregnancies. CONCLUSION: Our findings indicate that the increased placental expression of ecNOS mRNA might reflect a compensatory mechanism in the disturbed uterine circulation seen in PE and/or SGA.

Female↗

Role of nitric oxide in the regulation of vascular tone in pressurized and perfused resistance myometrial arteries from term pregnant women.

OBJECTIVE: Our purpose was to evaluate flow-induced responses, myogenic tone, and norepinephrine-induced constriction in myometrial resistance arteries from normal term pregnant women and the role that nitric oxide and prostanoids may play in these responses. STUDY DESIGN: Arteries (approximately 200 microns, n = 14, at 40 mm Hg) were dissected from myometrial biopsy specimens from women undergoing cesarean section and then were mounted in a pressure arteriograph. Responses to intraluminal flow, pressure, and a constrictor agonist (norepinephrine 10(-6) mol/L) were studied in the absence and presence of N omega-nitro-L-arginine methyl ester (n = 7) or indomethacin (n = 5). Myogenic and norepinephrine-induced tone were calculated after the determination of artery diameter in the absence of extracellular calcium. RESULTS: Arteries developed myogenic tone (80 mm Hg) that was not modulated by nitric oxide or prostanoid release, whereas norepinephrine-induced tone was significantly enhanced by the nitric oxide inhibitor. An increase in intraluminal flow led to dilatation in physiologic salt solution and indomethacin, but to constriction in the presence of N omega-nitro-L-arginine methyl ester (percent increase in diameter at flow rate of 184.6 microliters/min, 24% +/- 8% in physiologic salt solution and 20% +/- 4% in the presence of indomethacin versus -27% +/- 12% in N omega-nitro-L-arginine methyl ester alone and -21% +/- 10% in indomethacin and N omega-nitro-L-arginine methyl ester, respectively, analysis of variance, p < 0.05). CONCLUSIONS: Flow-induced shear stress is a physiologic modulator of vascular tone in myometrial arteries from pregnant women. Nitric oxide, but not prostanoids, mediates this response and also blunts norepinephrine constriction. Nitric oxide may play a fundamental role in the maintenance of adequate blood supply to the fetus during human pregnancy.

Arteries↗

A comparison of myogenic and endothelial properties of myometrial and omental resistance vessels in late pregnancy.

OBJECTIVE: Our purpose was to compare myometrial and omental resistance arteries from term pregnant women with respect to myogenic behavior in the presence or absence of a nitric oxide synthase inhibitor and to compare distensibility and acetylcholine-mediated dilatation in these vessels. STUDY DESIGN: Intramyometrial (n = 17) and omental (n = 14) resistance arteries from term normal pregnant women were studied in a pressurized arteriograph system. Myogenic tone was evaluated during increments in intraluminal pressure from 20 to 120 mm Hg with and without inhibition of nitric oxide synthase. Endothelium-dependent relaxation was assessed by evaluating the response to acetylcholine (10(-6) mol/L) in arteries pressurized at 70 mm Hg. RESULTS: Myogenic tone was greater at all pressure steps in the myometrial than in the omental arteries (p < 0.05). Inhibition of nitric oxide synthase with N(omega)-nitro-L-arginine had no influence on myogenic tone in either group. Relaxation to acetylcholine was greater in myometrial (18% +/- 4%) compared with omental vessels (7% +/- 2%, p < 0.05). The passive distensibility (Ca++-free solution and in the presence of papaverine) of arteries from the myometrium and the omentum was similar. CONCLUSION: Normal pregnancy is associated with different mechanical properties of resistance vessels from the two vascular beds studied. Basal nitric oxide release does not modify myogenic tone, at least under no-flow conditions. Acetylcholine-induced relaxation is greater in myometrial than in omental arteries.

Acetylcholine↗

Plasma endothelin in normal and diabetic pregnancy.

OBJECTIVE: To examine endothelin-1 (ET-1) concentrations longitudinally throughout pregnancy in healthy and insulin-dependent diabetic women and to evaluate the relationship between ET-1 and big ET-1 in normal pregnancy. RESEARCH DESIGN AND METHODS: Venous blood samples were obtained consecutively in gestational weeks 18, 28, and 38 from 40 healthy women with uneventful pregnancies and 24 pregnant women with IDDM. By radioimmunoassay, plasma ET-1 and big ET-1 were analyzed in the healthy women and plasma ET-1 in the diabetic women. RESULTS: In the diabetic pregnant women, plasma ET-1 levels were significantly higher than in healthy pregnant women during the entire observation period (P < 0.001), but did not change with advancing gestational age. Five of the diabetic, but none of the healthy pregnant women, developed preeclampsia. ET-1 levels did not differ between the diabetic women who developed preeclampsia and those who did not. Plasma ET-1 levels in healthy pregnant women were within the range of those in healthy nonpregnant women and did not change during pregnancy. The big ET-1 levels increased and the ET-1/big ET-1 ratio decreased significantly during the observation period. CONCLUSIONS: Plasma ET-1 levels do not change with advancing gestational length. During normal pregnancy, the ET-1/big ET-1 ratio decrease, indicating a suppressed converting enzyme activity or altered clearance of ET-1. Pregnant women with IDDM have markedly elevated ET-1 levels. Although diabetic women with and without preeclampsia did not differ with respect to endothelial dysfunction, as reflected by elevated ET-1 concentration, we cannot exclude that altered endothelial function may be of importance for the increased frequency of preeclampsia in pregnant IDDM patients.

Adult↗

Endothelin-1 and big endothelin-1 levels in normal term pregnancy and in preeclampsia.

To study the concentrations of endothelin-1 (ET-1) and its precursor, big ET-1, in samples of amniotic fluid, fetal urine, umbilical arterial and venous blood, retroplacental blood and maternal uterine and brachial venous blood obtained from normal and preeclamptic women. Samples were collected from 31 healthy pregnant women (16 in labor and 15 undergoing elective cesarean section) and 35 preeclamptic women (9 in labor and 26 undergoing cesarean section). Big ET-1 and ET-1 were measured by radioimmunoassay and the ET-1 to big ET-1 ratios were calculated. In preeclamptic women there was a significant elevation of ET-1 in the maternal brachial and uterine veins and of big-ET-1 in the brachial vein. The ET-1 concentrations and the ET-1/big ET ratios were significantly higher on the fetal side (i.e., in the umbilical vein and amniotic fluid) than in maternal blood, but in these sampling locations there was no difference between the normal pregnancy and preeclampsia group. A significant negative correlation (r = -0.67, P < 0.01) was found between plasma ET-1 in the umbilical vein and birth weight in the preeclamptic group. ET-1 was significantly higher in amniotic fluid than in the first neonatal urine of corresponding pregnancies (15.0 +/- 2.0 vs. 3.0 +/- 2.9 pmol/l, P < 0.05). The ET-1 and big ET-1 concentrations are significantly higher in fetal plasma and amniotic fluid than in maternal plasma, indicating increased endothelin converting enzyme activity and increased ET-1 production in utero. The elevated ET-1 concentration in maternal blood in preeclamptic compared with normal pregnant women and the negative correlation between ET-1 in the umbilical vein and birth weight suggest that ET-1 plays a pathophysiological role in preeclampsia and other conditions with intrauterine growth restriction.

Adult↗

Endothelin receptor type A and B gene expression in human nonpregnant, term pregnant, and preeclamptic uterus.

OBJECTIVE: The aim of this study was to quantify the gene expression of ETA and ETB receptors within the different uterine segments of nonpregnant, normal pregnant, and preeclamptic women. STUDY DESIGN: Biopsy samples from the cervix, isthmus, and corpus uteri were obtained from eight nonpregnant, nine term pregnant, and seven preeclamptic women. The concentration of ETA and ETB receptor messenger ribonucleic acid were determined by a solution hybridization technique with complementary ribonucleic acid probes. Results are presented in counts per minute per microgram of total nucleic acid as mean +/- SEM. RESULTS: The expression of messenger ribonucleic acid encoding the ETA receptor was generally higher in the upper than in the lower uterine segment in nonpregnant, normal pregnant, and preeclamptic myometrium, whereas the opposite pattern was seen with regard to ETB. During normal pregnancy the concentrations of ETA receptor messenger ribonucleic acid in the corpus and ETB receptor messenger ribonucleic acid in the isthmus were significantly elevated compared with those in nonpregnant women. This enhanced gene expression was, however, not observed in the preeclamptic group. CONCLUSION: Our finding of segmentally differentiated endothelin receptor gene expression is compatible with a role for endothelin-1 in stimulating uterine contractions through ETA receptors during spontaneous labor and suggests a relaxing effect of the ETB receptor on the myometrium.

Adult↗

Assessment of fetal fibronectin in cervical secretion in cases of equivocal rupture of the membranes at term.

BACKGROUND: To evaluate if the presence of fibronectin in cervical secretion might provide information on the natural course of equivocal prelabor rupture of membranes (ROM) at term. METHODS: One hundred and sixteen women with a history of prelabor ROM at term but without visible amniotic fluid leakage were included in the study. The presence of fetal fibronectin in cervical secretion was determined by a commercially available kit (ROM check; limit of detection 100 ng/ml). Women with (n=49) and without (n=67) a positive fibronectin test were compared with regard to time interval between presumed membrane rupture and delivery, mode of delivery and fetal distress rates. RESULTS: There was no significant difference in the time interval between presumed ROM and delivery between those with a negative fibronectin test (median: 80 hours) and those with a positive test (median: 64 hours; p=0.28, Mann-Whitney U-test). Neither were there any differences in complicated delivery or fetal distress rates. CONCLUSION: Determination of fetal fibronectin in cervical secretion with the present method is of limited value in the clinical management of patients with equivocal rupture of the membranes.

Adolescent↗

Effects of endothelin-1 and the ETA receptor antagonist BQ-123 on resistance arteries from normal pregnant and preeclamptic women.

OBJECTIVE: To compare the effect of endothelin on isolated resistance arteries from different vascular beds in normal and preeclamptic women before and after pretreatment with the ETA receptor antagonist BQ-123. MATERIALS AND METHODS: Resistance arteries from myometrial and omental biopsies obtained at cesarean section of normal pregnant and preeclamptic women were dissected and mounted in organ baths for recording of isometric tension. The contractile response to endothelin-1 in presence and absence of BQ-123 was recorded. RESULTS: Endothelin-1 induced similar concentration-dependent contractions in all arteries investigated. In women with preeclampsia the contractile response induced by endothelin-1 was significantly higher in omental as compared to myometrial vessels. Pretreatment with BQ-123 significantly shifted the concentration-response curve to the right but only reduced the maximum contractile response in omental vessels. CONCLUSION: Endothelin-1 is a potent constrictor of resistance arteries from different vascular beds in normal pregnancy and preeclampsia. The contractile effect is at least in part mediated by ETA receptors, since it was significantly reduced after pretreatment with BQ-123. In preeclamptic but not in normal pregnant women the response to endothelin-1 was reduced in myometrial as compared to omental arteries, possibly secondary to receptor down regulation.

Adult↗

Maternal renal artery blood flow velocimetry in normal and hypertensive pregnancies.

OBJECTIVE: To investigate the effect of normal pregnancy and hypertensive disorders of pregnancy on the maternal renal artery Doppler blood flow velocity indices. METHODS: The patient material consisted of 30 normal pregnant women, 29 women with pregnancy induced hypertension, 43 women with preeclampsia and 22 pregnant women with chronic hypertension. Blood flow velocities in the segmental renal arteries from the right kidney were analysed by pulsed and color Doppler. The systolic/diastolic (s.d.) ratio, resistance index (RI) and pulsatility index (PI) were used for Doppler waveform analysis. RESULTS: In all of the groups of hypertensive pregnant women renal artery Doppler indices were significantly lower compared to the normal pregnant women group. There was a significant negative relationship between renal artery PI and mean arterial pressure in the preeclampsia group and in the chronic hypertension group. CONCLUSION: The present results demonstrate that the mechanism of renal autoregulation in preeclampsia might be altered, leaving glomerulus unprotected from increased blood pressure. It seems that the concept of renal vasoconstriction in preeclampsia might be disputed and needs further investigation.

Diastole↗

Effects of nitroglycerin on the uterine and umbilical circulation in severe preeclampsia.

OBJECTIVE: To determine the effects of nitroglycerin on placental circulation in severe preeclampsia. METHODS: Twelve women with severe preeclampsia were examined. Uterine and umbilical artery pulsatility indices (PI) were assessed by pulsed Doppler ultrasound before and after infusion of nitroglycerin, starting at 0.25 micrograms/kg per minute with stepwise dosage increases until a diastolic blood pressure (BP) of 100 mmHg was achieved. Blood pressure and heart rate were recorded every 5 minutes. Blood was sampled for analysis of the second messenger of nitric oxide, cyclic guanosine monophosphate (cGMP), before and at the end of the infusion. RESULTS: During the infusion, the mean systolic BP decreased from 161 (95% confidence interval [CI] 154-169) to 138 mmHg (95% CI 131-146), and the diastolic pressure decreased from 116 (95% CI 111-122) to 103 (95% CI 96-110) mmHg (P < .01). The PI of the uterine artery did not change significantly (1.23 [95% CI 1.01-1.61]) versus 1.30 [95% CI 1.01-1.88]), whereas umbilical artery PI decreased significantly (P < .01), from 1.35 (95% CI 1.09-1.73) to 1.20 (95% CI 1.05-1.40), with a more pronounced decrease in patients with high basal values. Cyclic GMP remained essentially unchanged (6.4 [95% CI 5.4-7.7] versus 5.5 [4.7-6.6] nmol/L). CONCLUSION: The reduction in the PI of the umbilical artery during nitroglycerin-induced BP reduction implies vasodilation in the umbilical circulation. The absence of an increase in cGMP does not support the view that the nitroglycerin effect is reflected by the plasma concentration of cGMP.

Blood Pressure↗

Blood pressure and renal function seven years after pregnancy complicated by hypertension.

OBJECTIVE: To assess the occurrence of chronic hypertension and renal disorder after gestations complicated by pregnancy induced hypertension or pre-eclampsia and to define background factors and laboratory analyses at follow up examination which discriminate between women who remain normotensive and those who develop hypertension. SETTING: Swedish university hospital. SUBJECTS: Women with pregnancy induced hypertension (PIH) (n = 49), pre-eclampsia (n = 45) or a normotensive pregnancy (n = 44) during 1986. DESIGN: Subjects were reviewed in 1993 with regard to chronic hypertension and renal disorder. Plasma concentrations of creatinine, urea, uric acid, calcium and albumin were measured, and urine was examined for the presence of microalbuminuria and erythrocyte excretion rate. Those with and without hypertension at follow up were compared with regard to the renal function tests and possible features in the history which might predict chronic hypertension. RESULTS: Women with a history of pregnancy induced hypertension or pre-eclampsia had an increased risk, relative to controls, for hypertension at follow up (37% and 20% vs 2%; P < 0.001), microalbuminuria (14% and 20% vs 2%; P < 0.05) and demonstrated increased plasma levels of albumin corrected calcium (2.41 [SE 0.02] and 2.40 [0.01] vs 2.32 [0.01] mmol/l; P < 0.001). The only factors significantly associated with hypertension at follow up were the presence of microalbuminuria (P = 0.0008) and having had a delivery prior to the index pregnancy (P = 0.0017). CONCLUSIONS: The risk for chronic hypertension seven years after a pregnancy complicated with pregnancy induced hypertension or pre-eclampsia is considerably increased. The presence of hypertension at follow up is closely related to residual renal disorder.

Adult↗

Effects of atrial natriuretic peptide and cyclic guanosine monophosphate on isolated human myometrial arteries preconstricted by endothelin-1.

In the present in vitro study we investigated the possible vasorelaxing effect of atrial natriuretic peptide (ANP) and cyclic guanosine monophosphate (cGMP) on small intramyometrial arteries precontracted by endothelin-1 (ET-1). Myometrial biopsies from normotensive pregnant women were obtained during cesarean section and arteries of resistance vessel size were dissected and mounted in a tissue chamber for isometric registration of contractile tone. In arteries preconstricted with ET-1 (10(-8)M), ANP produced a concentration-dependent relaxation of 19 +/- 5% (mean +/- SEM) and 27 +/- 7% at concentrations of 10(-7) and 3 x 10(-7) M, respectively. cGMP induced a relaxation of 13 +/- 2, 18 +/- 3, 25 +/- 4 and 30 +/- 7% at concentrations of 10(-5), 10(-4), 3 x 10(-4) and 10(-3) M, respectively. Pretreatment with ANP did not attenuate the contraction produced by ET-1. We suggest that ANP may have a vasodilating effect on preconstricted human uteroplacental vessels. It also provides evidence for the role of other endogenous or exogenous vasodilators acting via cGMP-dependent mechanisms in the counteraction of ET-1-induced contraction of the myometrial resistance vessels during pregnancy.

Arteries↗