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Biomedical subjects

F Broughton Pipkin

Publications and source records attributed to F Broughton Pipkin.

At least 55 records · Page 3Linked to original sources
PubMed1994

Atrial natriuretic peptide in the preterm newborn.

Atrial natriuretic peptide (ANP), plasma renin and renin substrate concentrations (PRC and PRS) were measured in 31 preterm infants with idiopathic respiratory distress syndrome. Infants were studied at a mean of 1.4 days; 17 infants were also studied 2 days later. A 6-hour urine collection was made from 13 male infants on the first day of sampling to assess renal function. Both ANP and PRC were elevated and showed wide ranges of values (geometric means of 620 pg/ml and 18.4 ng/ml/h). Plasma ANP was significantly correlated with pH, PaCO2 and base excess. No correlations with parameters of cardiovascular or renal function were found. Plasma ANP rose in 13 of the 17 paired samples. We suggest that the very high ANP concentrations in these babies are a consequence of the pulmonary haemodynamic disturbances which accompany respiratory distress in the newborn.

Acid-Base Equilibrium↗
PubMed1993

Platelet cytosolic calcium in human pregnancy complicated by essential hypertension.

Five pregnant women whose pregnancies were complicated only by essential hypertension had significantly elevated platelet cytosolic calcium levels as compared with those of their normotensive counterparts. There seems to be an association between platelet cytosolic calcium level and arterial blood pressure that has previously been described in both nonpregnant and preeclamptic women.

Blood Platelets↗
PubMed1993

Changes in platelet intracellular free calcium in normal pregnancy.

OBJECTIVE: To determine if platelet intracellular free calcium concentration (p.(Ca2+)i) changes with gestation in normotensive, uncomplicated pregnancy. DESIGN: A prospective, longitudinal study of primigravid pregnant women compared to a large control group consisting of nulliparous nonpregnant volunteers. SETTING: The antenatal clinic at University Hospital, Queen's Medical Centre, Nottingham. SUBJECTS: Two groups of women were studied. Thirty-one nulliparous, nonpregnant women not using oral contraception were investigated in the early follicular phase of their menstrual cycles. Also, 24 primigravid women with normotensive, uncomplicated pregnancies were investigated on eight separate occasions during their pregnancies. RESULTS: A significant increase in mean p.(Ca2+)i was demonstrated by 28 weeks gestation in the pregnant women as compared to the nonpregnant control group and the same individuals when investigated at 12 weeks postpartum (P < 0.05; ANOVA). This change was maximal at 36 weeks gestation (P < 0.001; ANOVA); concentrations had returned to those not significantly different from nonpregnant women by six weeks postpartum. CONCLUSIONS: Basal platelet (Ca2+)i increases significantly by the third trimester of normal, primigravid pregnancy as compared to pregnancy values and postnatal values. These data mirror the previously described observations of platelet behaviour noting increased activity at this gestation of pregnancy. It may be that the increased basal p.(Ca2+)i indicates that smaller transient signals have to be generated to induce platelet activity, such as shape change, aggregation and exocytosis.

Adult↗
PubMed1993

Pressor, heart rate and plasma catecholamine responses to noradrenaline in pregnant and nonpregnant women.

OBJECTIVE: To study cardiovascular responses to noradrenaline during early pregnancy. DESIGN: Administration of incremental intravenous infusions of noradrenaline under basal conditions. SETTING: University Hospital, Nottingham. SUBJECTS: Nineteen women admitted for termination of pregnancy in first or second trimester and 18 nonpregnant women as control subjects. INTERVENTIONS: Recordings of blood pressure and heart rate responses during the infusion of noradrenaline. Blood samples taken before, during and after the infusion. MAIN OUTCOME MEASURES: Evoked responses of systolic and diastolic blood pressure and heart rate at steady state during the noradrenaline infusion. Plasma catecholamine concentrations measured by high performance liquid chromatography. RESULTS: There were no significant differences between the evoked pressor responses to noradrenaline in pregnancy compared to the nonpregnant state, but there was a lesser bradycardia in response to a standardised change in blood pressure. Neither basal plasma catecholamine concentrations nor those achieved during infusion of noradrenaline differed between pregnant and nonpregnant women. Thirty minutes after discontinuance of the infusion there was a persistent elevation of heart rate in all women, although plasma catecholamine concentrations had returned to basal levels. In pregnant women, systolic and diastolic blood pressures were also elevated at this time, compared to preinfusion levels. CONCLUSION: Cardiovascular regulatory mechanisms are altered in pregnancy with a diminution in the bradycardic response to a pressor challenge evoked by noradrenaline and a delayed recovery from that challenge.

Adult↗
PubMed1992

Comparative study of pressor and heart rate responses to angiotensin II and noradrenaline in pregnant and non-pregnant women.

1. Twenty-eight healthy non-pregnant women and 28 women in the first or second trimester of pregnancy were studied. They were given an incremental intravenous infusion of either noradrenaline or angiotensin II. Pressor and heart rate responses were documented. 2. Dose-pressor response curves were constructed for the two agents in pregnant and non-pregnant women (n = 14 in each group). The regression parameters of slope and intercept were calculated, and were used to derive the variables of dose required to elicit a 10 mmHg rise in systolic or diastolic blood pressure. 3. The pressor response to angiotensin II was diminished in pregnancy, with approximately twice the dose being required to raise the systolic or diastolic arterial blood pressure as in non-pregnant subjects. 4. The systolic pressor response to noradrenaline was slightly diminished in pregnancy, but the diastolic pressor response was unchanged. There were no significant differences between the doses of noradrenaline required to elicit a 10 mmHg rise in systolic or diastolic arterial blood pressure in pregnant or non-pregnant subjects. 5. There was a diminution in the bradycardia evoked in response to both hormones in pregnancy. 6. We conclude that the well-documented pressor insensitivity to angiotensin II during pregnancy is a specific phenomenon, not a manifestation of a generalized reduction in vascular reactivity.

Angiotensin II↗
PubMed1992

Longitudinal study of platelet angiotensin II binding in human pregnancy.

1. Platelet angiotensin II binding, circulating angiotensin II levels, plasma renin substrate and plasma renin concentration were measured in a longitudinal study of 30 women during pregnancy and the puerperium. 2. There was a significant fall in platelet angiotensin II binding from 11 weeks gestation to 18 weeks gestation (P less than 0.01). There were no further significant changes in platelet angiotensin II binding until after delivery, a significant rise in platelet angiotensin II binding being found at 6 weeks post partum as compared with at 36 weeks gestation (P less than 0.01). There was no further significant change from 6 to 12 weeks post partum, and platelet angiotensin II binding at 6 and 12 weeks post partum in the pregnant cohort approximated to that in nonpregnant women. These changes parallel those known to occur in pressor responsiveness to angiotensin II in pregnancy. 3. Plasma angiotensin II concentration, plasma renin substrate and plasma renin concentration were all significantly higher during pregnancy than in the puerperium (P less than 0.001). There were no significant changes during pregnancy in plasma angiotensin II concentration or plasma renin concentration, although plasma renin substrate rose throughout. 4. Significant inverse correlations between platelet angiotensin II binding and plasma angiotensin II concentration (P less than 0.01), plasma renin substrate (P less than 0.01) and plasma renin concentration (P less than 0 greater than 001) were found during pregnancy. These data suggest that down-regulation of platelet angiotensin II binding by the components of the renin-angiotensin system pertains in pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1992

Comparative study of platelet angiotensin II binding and the angiotensin II sensitivity test as predictors of pregnancy-induced hypertension.

1. Platelet angiotensin II binding was measured in 34 primigravid women (between 28 and 32 weeks gestation), in whom the pressor response to infused angiotensin II was also determined. 2. There was a significant correlation between the platelet angiotensin II binding and the slope of the curve relating the diastolic pressor response to infused angiotensin II (P less than 0.01), suggesting that co-linearity between the two techniques exists and supporting the use of platelet angiotensin II binding as a model of vascular smooth muscle pressor responsiveness. 3. Ten of the 34 women subsequently developed pregnancy-induced hypertension. Platelet angiotensin II binding in the patients who subsequently developed pregnancy-induced hypertension was sixfold higher than in the patients who remained normotensive (P less than 0.001). There were, however, no significant differences between the groups in any of the parameters derived from the angiotensin II infusion experiments. 4. The use of platelet angiotensin II binding alone in predicting the outcome of the pregnancies, as assessed using discriminant analysis, was more successful than when any of the infusion parameters were used, with 77% of patients being correctly classified.

Adult↗
PubMed1992

The effect of angiotensin II on platelet intracellular free calcium concentration in human pregnancy.

OBJECTIVES: The primary objective of this study was to determine the effect of i.v. angiotensin II infusion on platelet intracellular free calcium concentration in potentially hypertensive primigravid women. DESIGN: Patients at 28-32 weeks gestation were selected on the basis of a diastolic pressure less than or equal to 80 mmHg taken at the antenatal clinic visit. METHODS: An angiotensin II infusion test (4-16 ng/kg per min) was performed in 13 women. Platelet intracellular free calcium concentration, platelet angiotensin II binding site density and plasma angiotensin II concentration were measured before and at the end of the infusion. Pregnancy outcome (normotension or hypertension) was recorded. RESULTS: Platelet intracellular free calcium concentration rose in 12 of 13 women during angiotensin II infusion. This rise was not directly correlated with initial or final platelet angiotensin II binding site density, plasma angiotensin II concentration or the evoked change in systolic or diastolic blood pressure. Five women subsequently developed pregnancy-induced hypertension. Although basal platelet intracellular free calcium concentration did not differ between the two groups, platelet intracellular free calcium concentration rose twice as much in response to angiotensin II in the five hypertensive pregnant women. There was a 12-fold increase in platelet angiotensin II binding in the future hypertensives, although basal angiotensin II was the same in the two groups. CONCLUSION: The enhanced rise in platelet intracellular free calcium concentration in response to angiotensin II administration in women who subsequently became hypertensive, together with their increased angiotensin II binding site density suggest a possible enhanced stimulus-effect coupling. Pregnancy-induced hypertension is a state of marked vasoconstriction, with an enhanced pressor response to angiotensin II. These data supply grounds for a hypothesis concerning the mechanism.

Adult↗
PubMed1992

A randomised placebo controlled trial of labetalol in the treatment of mild to moderate pregnancy induced hypertension.

OBJECTIVE: To determine the need for, and efficacy of, treatment with labetalol in women with mild-to-moderate pregnancy induced hypertension (PIH). DESIGN: Prospective double-blind randomised placebo controlled study. SETTING: Maternity units of five hospitals in the Trent Region. SUBJECTS: 144 women (86 primigravid) who developed PIH after 20 weeks gestation. INTERVENTIONS: Treatment with oral labetalol up to 600 mg daily or placebo with subsequent care of treatment failures in accordance with the attending obstetrician's practice. MAIN OUTCOME MEASURES: Number of days spent as an antenatal inpatient; the development of proteinuria; the perceived need for induction of labour or elective caesarean section; and gestation age at delivery. RESULTS: Labetalol significantly lowered the blood pressure and reduced the incidence of proteinuria. However, neither the number of days spent as an antenatal inpatient, nor the perceived need for induction of delivery or elective caesarean section, nor the gestation age at delivery differed significantly between the two treatment groups. Post-randomisation consideration of early (< or = 32 weeks) and late (> 32 weeks) onset groups showed the placebo treated early-onset group (n = 15) to have more patients with severe hypertension (> 150/110 mmHg) and a greater requirement for additional antihypertensive therapy prior to labour than the group treated with labetalol (n = 16). CONCLUSION: Anti-hypertensive intervention therapy in pregnancy induced hypertension has been examined using a placebo controlled randomised double-blind trial of labetalol in pregnancy. The maximum blood pressure prior to labour and the incidence of proteinuria was reduced in women on active therapy. However, the length of gestation was not significantly prolonged and indices of clinical outcome were not significantly altered. The appropriateness of pharmacological therapy for late-onset PIH may be questioned.

Administration, Oral↗
PubMed1992

A randomized placebo-controlled study of the effect of low dose aspirin on platelet reactivity and serum thromboxane B2 production in non-pregnant women, in normal pregnancy, and in gestational hypertension.

OBJECTIVE: To investigate the effect of 60 mg aspirin daily on platelet reactivity and prostaglandin production in various groups of patients. Similar regimens, which are thought to act through inhibition of platelet thromboxane production, are currently undergoing clinical assessment for the prevention of pre-eclampsia and intrauterine growth retardation. DESIGN: A prospective randomized placebo controlled study. SETTING: University Hospital, Nottingham. SUBJECTS: 12 non-pregnant female volunteers, 18 normal primigravidae before 16 weeks gestation and 16 pregnant women admitted with gestational hypertension (GH) at a mean gestation of 38 weeks. INTERVENTIONS: In the non-pregnant women blood samples were taken before and after a 10-day course of 60 mg aspirin daily. The primigravidae had blood samples taken at 16 weeks and then they were randomized to receive either 60 mg aspirin daily or a matched placebo. Further blood samples were obtained at 28, 32 and 36 weeks. MAIN OUTCOME MEASURES: Changes in platelet reactivity and release reaction, and serum thromboxane production, were estimated in whole blood. RESULTS: 60 mg aspirin daily significantly inhibited cyclo-oxygenase dependent platelet aggregation, release reaction and serum thromboxane production in non-pregnant and pregnant women, and in women with GH (P less than 0.01). When adrenaline was used as the aggregating agent, the cyclo-oxygenase pathway was recruited in the increased reactivity seen in the third trimester of normal pregnancy, and was sensitive to inhibition by low dose aspirin. CONCLUSION: Low dose aspirin would appear to be an appropriate agent for the inhibition of platelet reactivity associated with hypertensive pregnancy.

Adult↗
PubMed1992

Calcium and platelets in normotensive and hypertensive human pregnancy.

OBJECTIVES: The primary objective of this study was to determine the baseline platelet intracellular free Ca2+ concentration in normotensive and hypertensive primigravid women and to note any correlation between variables (ie. platelet intracellular free Ca2+ concentration and arterial blood pressure). DESIGN: A cross-sectional study of 24 normotensive and 36 primiparous women whose pregnancies were complicated by gestational hypertension, in the third trimester. METHODS: Platelet intracellular free Ca2+, serum Ca2+, and renal clearance of Ca2+ were recorded. RESULTS: Mean platelet intracellular free Ca2+ concentration was significantly increased in those subjects whose pregnancies were complicated by proteinuric gestational hypertension (pre-eclampsia) compared with the normotensive primiparous control sample. Those subjects with non-proteinuric pregnancy-induced hypertension did not show this significant increase in baseline platelet intracellular free Ca2+ concentration despite having a persistent and statistically significantly elevated systemic arterial blood pressure. On pooling these data for both normotensive and hypertensive primigravidae a significant positive correlation was noted between the variables of platelet intracellular free Ca2+ concentration and arterial blood pressure. The renal clearance of free Ca2+ was progressively reduced with increasing severity of the disease but had returned to normal 6 weeks postpartum. Serum Ca2+ concentrations corrected for albumin were however higher in the hypertensive patients. CONCLUSION: Transmembrane Ca2+ fluxes are altered in hypertensive pregnancy by a specific mechanism, probably of placental origin.

Adult↗
PubMed1991

The influence of angiotensin II-induced vasoconstriction on common carotid artery blood flow and velocity-time profiles in normal women.

Non-invasive methods of measuring blood velocity, especially Doppler velocimetry, are being increasingly used in obstetrics to provide observational information. We report a preliminary study of their usefulness in experimental studies. Doppler velocimetry was used to assess blood flow and velocity-time profiles in the common carotid artery of seven women of reproductive age before and during the incremental administration of angiotensin II. Angiotensin II infusion evoked the expected increments in systolic and diastolic arterial pressure and fall in heart rate. Angiotensin II was associated with a dose-dependent fall in maximum blood velocity, which, at an average rise in systolic blood pressure of 23 mmHg, had fallen from 91 +/- 16 to 52 +/- 4 (mean +/- SD, p < 0.01). Absolute maximum blood velocity was strongly correlated with systolic and diastolic blood pressures (p < 0.001 for both). The minimum velocity was unaltered throughout, and the calculated flow did not change significantly (490 +/- 100 cf. 380 +/- 50 ml/min). Overall, these findings are in agreement with those previously reported using invasive methods of monitoring flow during angiotensin II infusion, and further support the usefulness of Doppler velocimetry as an investigative tool in human physiology and pharmacology.However, the pulsatility index, resistance index and systolic/diastolic velocity ratio all fell significantly during angiotensin II infusion (p < 0.01 for all). The conventional interpretation of a fall in these indices, i.e. reduced downstream resistance, is clearly erroneous under these circumstances, since angiotensin II induces arteriolar vasoconstriction. This illustrates the importance of interpretation of Doppler velocity envelopes in the light of pharmacological mechanisms likely to be evoked by the experimental procedure.

Journal Article↗