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Biomedical subjects

F Broughton Pipkin

Publications and source records attributed to F Broughton Pipkin.

At least 109 records · Page 6Linked to original sources

Imaging the pregnant human uterus with nuclear magnetic resonance.

Nuclear magnetic resonance (NMR) techniques have been used to produce images of the pregnant and nonpregnant human uterus. A series of pictures is presented showing the normal nonpregnant uterus and pelvic organs, the uterus and its contents in pregnancy at 17, 30, and 40 weeks' gestation, and the pelvic organs in the early puerperium. In early pregnancy the uterus and placenta are clearly seen and the dimensions and configuration of the pelvis can be readily assessed. Because of the relatively long scan time of 2 minutes, better images of the fetus were obtained in the third trimester when movement is more restricted. The potential value of this technique in obstetrics is discussed.

Female↗

The effect of prostaglandin E2 upon the biochemical response to infused angiotensin II in human pregnancy.

The effects of angiotensin II infusion without and with simultaneous infusion of prostaglandin E2 were studied in 25 women in second trimester pregnancy. Twenty received one infusion of angiotensin II alone, followed by its infusion simultaneously with prostaglandin E2; five received two identical infusions of angiotensin II alone as controls. Angiotensin II infusion alone was associated with suppression of plasma renin concentration to levels inversely proportional to the evoked change in diastolic blood pressure. Plasma renin substrate concentration was unchanged, but plasma aldosterone concentration rose markedly. This rise was inversely proportional to the threshold for pressor effect of angiotensin II. Prostaglandin E2 administration alone was associated with increased plasma renin concentrations. The pressor effect of angiotensin II was blunted when given together with prostaglandin E2 and plasma concentrations of angiotensin II reached were lower. Plasma renin concentration was again suppressed during the joint infusion regimen; the degree of suppression was inversely proportional to the change in diastolic pressure. Plasma aldosterone concentration rose, but did not differ in the control and experimental groups. Thus although the renin-angiotensin system is stimulated in normal pregnancy, the normal control mechanisms are still functional, and the capacity for further increases in activity exists.

Adolescent↗

Studies on equine prematurity 1: Methodology.

This paper describes the general management of mares and foals during the perinatal period and the methodology used in a collaborative research project on equine prematurity. Sixteen mares with dated pregnancies delivered 45 foals over three breeding seasons (1981 to 1983). In the majority, parturition was induced with oxytocin and/or fluprostenol; the remainder were allowed to foal spontaneously. Pre-colostral milk analysis provided a means of assessing the pre-foaling status of the mare. All were observed and monitored before, during and after parturition and the sampling protocol for both mare and newborn foal is discussed in detail. The foals were assessed for their degree of maturity at birth using behavioural, haematological, acid-base status and other criteria; they were then assigned to groups for further study and tests.

Animals↗

Studies on equine prematurity 4: Effect of salt and water loss on the renin-angiotensin-aldosterone system in the newborn foal.

Plasma renin substrate concentration was measured in 18, four-day-old pony foals after the administration of the natriuretic agent frusemide. Thirteen foals had been delivered spontaneously; labour had been induced in the remaining five mares. Plasma aldosterone concentration was measured in 12 of the spontaneously delivered foals. Renin substrate concentration had risen sharply within 15 mins (P less than 0.005) and peaked at 1 h. The response was consistently greater in the induced foals. Serum sodium concentration fell rapidly in the induced foals (P less than 0.002 by 60 mins) but was better maintained in the spontaneous group. Individual serum potassium concentrations varied widely and were higher in both the induced group and smaller (30 kg or less) spontaneous foals. Plasma renin substrate concentration was positively correlated with plasma potassium in both groups (P less than 0.05, P less than 0.001 respectively). Plasma aldosterone rose significantly within 30 mins (P less than 0.025) and did not stabilise during the experiment. Plasma aldosterone was significantly correlated with renin substrate concentration in both lighter (P less than 0.005) and heavier (P less than 0.05) spontaneously delivered foals. It is suggested that maturation of renal sodium and potassium handling occurs late in gestation in the foal and is in part related to body mass. 'Premature' delivery following induced labour is associated with a more rapid loss of sodium when challenged with frusemide, even though the response of the renin-angiotensin system may be exaggerated.

Aldosterone↗

The effect of saralasin in the chronically cannulated ewe in the early puerperium.

The effects of angiotensin II receptor blockade with saralasin ((sar1) (ala8) angiotensin II) have been studied 1-3 days post partum in seven ewes with indwelling vascular cannulae. Control experiments were performed 48 h later in five of the same ewes. The infusion of saralasin at 1, 2, 4 and 8 micrograms kg-1 min-1 resulted in an initial small pressor response, followed by a depressor effect. A significant inverse correlation was demonstrated between log10 dose saralasin and the evoked change in diastolic blood pressure (r = -0.5891, P less than 0.005). A small and inconsistent depressor effect was found in the control experiments; there was no evidence for an association between dose and response (r = +0.0411, P greater than 0.85). These data were compared with those from a previously published study in which an identical infusion protocol for saralasin was used in ten chronically cannulated pregnant ewes. The slopes of the two dose-response curves were very similar (-14.9 +/- 4.3 post partum compared with -14.2 +/- 4.2) in the two groups. However, the average response was greater in the pregnant group, by 7.6 +/- 1.2 mmHg (P less than 0.005). Plasma renin concentration rose significantly during saralasin infusion (P less than 0.05) but was unchanged in control experiments, indicating blockade of the renin-angiotensin system by the removal of negative feed-back control by angiotensin II. Saralasin is known to exert an agonist effect when angiotensin II itself is not directly concerned in the regulation of arterial blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Aldosterone↗

The effect of changes in blood gas tension upon the renin-angiotensin system of the newborn infant.

Renin and renin-substrate concentrations were measured in the paired umbilical artery and vein blood of 20 babies born by elective caesarean section, and 36 babies born vaginally. Blood pH, carbon dioxide tension and oxygen tension were measured in all samples. Babies born vaginally were significantly more acidaemic than those delivered by caesarean section. The cord artery blood also had a significantly greater carbon dioxide tension at vaginal delivery. A decrease in pH of either cord artery or vein blood, irrespective of mode of delivery, was associated with an increase in renin concentration. Renin-substrate concentration tended to be lower in the cord vein blood of acidaemic babies born vaginally, such that the ratio renin: renin-substrate concentration was negatively correlated with pH. At caesarean section the renin concentration of cord vein blood was positively correlated with carbon dioxide tension and increased dramatically at oxygen tensions less than 3kPa. This was not observed in babies born vaginally, but the cord artery substrate concentration in these infants was positively correlated with carbon dioxide tension. Thus changes in the renin-angiotensin system at birth may partly be affected by blood gas tension.

Adolescent↗

Studies on the effect of mode of delivery on the renin-angiotensin system in mother and fetus at term.

Plasma renin substrate (PRS) and renin (PRC) concentrations were measured in the paired umbilical artery and vein blood of 54 babies and in the venous blood of 23 of their mothers at vaginal delivery. Similar samples were collected from 31 babies and their mothers at elective caesarean section. Fetal renin concentrations in both umbilical artery and vein blood were markedly increased at vaginal delivery compared with values at operative delivery. Renin substrate concentration was correlated with the length of second stage of labour. Umbilical vein PRC and PRS were greater than corresponding umbilical artery values at vaginal, but not at operative delivery, suggesting that some factor associated with delivery might stimulate the placenta to produce renin and renin substrate during vaginal delivery. Maternal and umbilical concentrations of both renin and renin substrate were unrelated, supporting the view that the maternal and fetal compartments are independent. It is suggested that hyperactivity of the renin-angiotensin system may be an integral part of the marked changes in cardiovascular homeostasis which occur at birth.

Adult↗

Effects on the renin-angiotensin system of the administration of prostaglandin E1 and E2 in second trimester human pregnancy.

We have measured evoked changes in plasma renin concentration (PRC), plasma renin substrate (PRS) amd plasma aldosterone concentration (ALD) during the infusion of angiotensin II (AII) with and without the simultaneous administration of prostaglandin E2, 5 micrograms min-1 i.v. (PGE2) or prostaglandin E1, 15 ng kg-1 min-1 (PGE1). Experiments have been carried out using PGE2 in 20 patients, and in 5 patients to date with PGE1. AII alone (16 ng kg-1 min-1 i.v.) significantly reduced PRC in both groups of patients without altering PRS, while ALD concentrations more than doubled. The infusion of PGE2 stimulated basal PRC; PGE1 at the dose used did not alter PRC. Neither prostaglandin altered basal RS or ALD concentrations. When AII was infused simultaneously, PRC was again suppressed, in the presence of PGE2. However, only minimal feedback suppression occurred when PGE1 was being used. Furthermore, AII was still associated with a more than two-fold rise in ALD concentration when given together with PGE2, but the rise was considerably smaller and not significant in the presence of PGE1. PGE2 is a known stimulus to renin secretion, apparently acting directly at the juxtaglomerular apparatus. These preliminary results suggest that while a similar mechanism exists in second trimester human pregnancy, PGE1 may have a different effect. The apparent blockade of the normal feedback suppression of PRC in the presence of increased PGE1 concentrations by raised concentrations of AII is especially interesting.

Adult↗

The effect of essential fatty acid and specific vitamin supplements on vascular sensitivity in the mid-trimester of human pregnancy.

Vascular sensitivity to angiotensin II was determined in the mid-trimester of pregnancy in women after taking a diet with supplemented essential fatty acids and vitamins. The essential fatty acids linoleic and dihommogammalinolenic acid were administered as evening primrose oil capsules (Efamol) for one week prior to the study. Vascular sensitivity was then determined in response to 4, 8 and 16 ng kg-1 min-1 angiotensin II. Vitamin supplements (Efavit) were given with the Efamol capsules. Seven women have been studied, and their vascular sensitivity compared with controls on normal diet. The vascular sensitivity was significantly reduced in all the patients on essential fatty acid supplements, and all values fell below the mean of the control group.

8,11,14-Eicosatrienoic Acid↗

Renin and aldosterone concentrations in pregnant essential hypertensives - a prospective study.

Serial blood samples were obtained throughout pregnancy from 11 women with essential hypertension (EHT). Seven were treated with labetalol (Trandate) and 4 with alpha -methyl dopa (Aldomet). Nine patients were well-controlled throughout pregnancy. Their mean plasma renin concentrations (PRC) followed the profile determined in 18 normal patients studied serially. They remained in the upper normal range until the last month, when both treatment groups showed a fall in PRC. Mean plasma aldosterone (ALD) also followed a normal profile until late gestation when it too showed a sharp fall. Of the two patients who developed superimposed PIH, one, who received labetalol, developed severe hypertension at 35 weeks, requiring delivery. Although PRC increased early in this pregnancy, ALD did not, remaining low throughout. Serum potassium [K+] measurements were also very low in this patient. The second patient only became hypertensive at 40 weeks and had PRC and ALD profiles resembling those in the successfully treated EHTs. There was a strong positive correlation throughout between serum potassium and ALD measurements (p less than 0.001) but none between PRC and ALD. This latter agrees with the known lack of correlation between PRC and ALD in normal pregnancy and may suggest that changes in electrolyte balance are more important stimuli to ALD secretion during pregnancy.

Adult↗

The effects of anesthesia and mode of delivery on the parameters of the renin-angiotensin system.

Paired maternal venous (MV) before (P1) and after (P2) general anesthesia, cord venous (CV) and cord arterial (CA) blood was taken from two groups of primagravid women, one delivered vaginally and the other by elective lower segment Caesarian section (ELSCS). ACTH, Cortisol (CoSol) Aldosterone (Aldo) Plasma Renin Activity (PRA) Plasma Renin Concentration (PRC) Angiotensin II (AII) Solium (N alpha) and Potassium [K]+ were measured in both study groups. Of the various hormones studied, all but cortisol were raised in the P2 sample with only ACTH and AII achieving significant increase. A number of significant positive correlations was found between P1 and P2 samples as well as between the hormones themselves. Four of the vaginally delivered group received epidural analgesia and demonstrated significantly higher levels of ACTH and CoSol in the CV sample. A comparison of the studied variables between the two groups showed a significant decrease in the ELSCS group of ACTH and CoSol in the MV sample, of ACTH, CoSol, PRC in the CV sample, and of CoSol in the CA sample. Of all the parameters, studied, only [K]+ together with Aldo was found to be elevated in the CV sample of the ELSCS group but only [K]+ achieved significant increase.

Adrenocorticotropic Hormone↗

Ketamine hypertension and the renin-angiotensin system.

Renin and angiotensin II have been measured before and 10 minutes after anaesthesia, in 23 patients undergoing minor gynaecological surgery. Twelve were anaesthetised with ketamine 2 mg/kg i.v. and the remainder with thiopentone 5-10 mg/kg i.v. Arterial blood pressure was monitored automatically throughout. The arterial blood pressure rose significantly in the group given ketamine and plasma AII concentration fell. In the group given thiopentone there was no significant overall change in blood pressure but an increase in AII. Plasma renin concentration and activity showed significant increases following the administration of ketamine but were unchanged following thiopentone. Overall, there was a significant inverse relationship between the change in blood pressure and the change in AII. This is compatible with a negative feedback being exerted on the renin-angiotensin system by the raised blood pressure, which has itself been evoked by some quite different factor or factors. We conclude that the renin-angiotensin system is not concerned in the pressor response to ketamine.

Adult↗

Prostaglandin E2 attenuates the pressor response to angiotensin II in pregnant subjects but not in nonpregnant subjects.

The effect of prostaglandin E2 (PGE2), 5 microgram/min-1, on the pressor response to exogenous angiotensin II (AII) has been examined in 22 women in second-trimester pregnancy and in 10 nonpregnant control subjects. PGE2 diminished the diastolic pressor response in both groups without altering basal blood pressure. This effect was significant in the pregnant group, and not significant in the nonpregnant patients. The effect was achieved by a significant increase in threshold to AII, rather than an alteration in the slope of the dose-response curve. Five pregnant patients who were given two identical infusion regimes of AII without PGE2 showed no diminution of response. The effect of PGE2 was greatest in the pregnant women who showed greatest initial sensitivity to AII, perhaps suggesting a relative deficiency of E series prostaglandins in some women by midtrimester pregnancy.

Adolescent↗

Changes in the renin-angiotensin-aldosterone system in normotensive primigravidae in the four days after normal spontaneous delivery.

Plasma renin activity, plasma renin concentration, plasma renin substrate, plasma angiotensin II and plasma aldosterone were measured in 10 true primiparae, normotensive throughout pregnancy, for 4 days after a spontaneous vaginal delivery. The concentration of all the measured variables, except plasma renin substrate, fell steeply over the first 3 days post partum. In four of the 10 patients, all components of the renin-angiotensin system increased in concentration somewhat thereafter, although not to the levels of the first day post partum. There are multiple potential sources of renin in the fetoplacental unit and it is possible that this 'pregnancy' renin may be capable of the partial suppression of the maternal renin production during pregnancy. The slight rebound observed in some patients may represent a hunting for re-establishment of non-pregnant values.

Adolescent↗

The effect of captopril (SQ14,225) upon mother and fetus in the chronically cannulated ewe and in the pregnant rabbit.

1. An inhibitor of angiotensin-I-converting enzyme activity (D-3-mercapto-2-methylpropanoyl-L-proline, Captopril) was given to five chronically cannulated pregnant ewes and eleven rabbits in late pregnancy. 2. Within 2 min of administration to the sheep, Captopril had blocked the maternal conversion of angiotensin I to II, as assessed by the pressor response evoked by the i.v. administration of angiotensin I. Maternal and fetal basal systemic blood pressures had fallen within 10 min of administration. Although maternal systemic blood pressure returned to basal levels within 2 hr, fetal pressures remained low for up to 2 days. 3. All ewes went into spontaneous labour at or near term. One lamb was live-born but very weak and failed to establish suckling. The remaining seven lambs were fresh still-births. 4. Gestation length was significantly prolonged in the treated rabbits by comparison with ten controls. The still-birth rate was 37% in the treated animals and 6% in the controls (P less than 0.001). 5. It is concluded that the administration of Captopril to the two species studied is harmful to the fetus. The observations suggest that the drug rapidly crosses the placenta, and may cross the blood-brain barrier to exert a central effect. It may also interfere with the normal initiation of parturition.

Aldosterone↗