Peggy J. Whalley

A Study of Angiotensin II Pressor Response throughout Primigravid Pregnancy

The present study was designed to ascertain sequentially the pressor response to angiotensin II in young primigravid patients throughout pregnancy in order a) to define when in pregnancy resistance to the pressor effects of angiotensin II develops; b) to define the physiologic sequence of events leading to this resistance; and c) to ascertain whether sensitivity to infused angiotensin II could be detected before the onset of clinical signs of pregnancy-induced hypertension. With this prospective approach, two separate groups of patients were defined. The first group of patients remained normal throughout pregnancy. The second group consisted of those patients who, while clinically normotensive during the initial phase of the study, ultimately developed hypertension of pregnancy.192 patients were studied; of these, 120 patients remained normotensive and 72 developed pregnancy-induced hypertension. In both groups, vascular resistance to infused angiotensin II (more than 8 ng/kg/min required to elicit a pressor response of 20 mm Hg in diastolic pressure) was demonstrated as early as the 10th wk of pregnancy. In the group that remained normotensive, maximum mean vascular resistance occurred at 18-30 wk of pregnancy, (mean pressor dose required being 13.5 to 14.9 ng/kg/min). In those subjects who developed pregnancy-induced hypertension, the mean maximum dose required was 12.9 ng/kg/min, which was observed at the 18th wk of pregnancy. By the 22nd wk there was a clear separation of the two groups, with the mean dose requirement of the subjects destined to develop hypertension being progressively less than that of those who remained normal. The difference between the two groups became significant (P < 0.01) by 23-26 wk of pregnancy. Among patients requiring more than 8 ng/kg/min on one or more tests done between wk 28-32, 91% remained normotensive. Conversely, during the same time period among patients requiring less than 8 ng/kg/min, on at least one occasion, 90% developed pregnancy-induced hypertension.

Control of Vascular Reactivity in Pregnancy

Human pregnancy is characterized by a blunted pressor responsiveness to vasopressor substances. This was first reported by Dieckmann and Michel in 1937 in experiments in which they measured vascular reactivity to the pressor effects of a crude preparation of vasopressin. Recently, this has been reported to occur in response to epinephrine, norepinephrine (NE), and angiotensin II (AII). Gant and associates reported that the increasing vascular sensitivity to infused AII not only was characteristic of women who developed pregnancy-induced hypertension, but in fact preceded the development of pregnancy-induced hypertension. Although a variety of factors may mediate this blunted pressor responsiveness, the most likely candidate appears to be the localized production within endothelium and/or vascular smooth muscle of prostaglandins. Indeed, administration of indomethacin or aspirin results in an increased sensitivity to infused AII in normotensive previously AII-refractory women. Administration of the steroid hormone 5 alpha-dihydroprogesterone reverses this apparent prostaglandin-mediated response. In addition, administration of the phosphodiesterase inhibitor, theophylline, results in a restoration of vascular refractoriness to infused AII in women with pregnancy-induced hypertension or in women destined to develop pregnancy-induced hypertension. Although a variety of known and possibly unknown compounds might also effect the control of vascular reactivity during human pregnancy, the prostinoids appear to play a pivotal role in mediation of control of vascular reactivity during human pregnancy.

The effects of maternal sickle cell hemoglobinopathies and sickle cell trait on reproductive performance

Abstract Reproductive performances have been analyzed for 797 black women whose red cells contain sickle cell hemoglobin. Fifty pregnancies in 34 women with sickle cell anemia yeilded only 27 infants who survived; there were no maternal deaths, but morbidity was frequent and often intense. Seventy-eight pregnancies in 43 women with sickle cell-hemoglobin C disease culminated in the births of 68 infants who survived; serious maternal morbidity was common, and 2 women died. Thirty-two infants survived from 37 pregnancies in 21 women with sickle cell-beta thalassemia disease; maternal morbidity was comparable to that with sickle cell-hemoglobin C, disease but there were no maternal deaths. The pregnancy experiences for women with sickle cell trait were not different from those of black women whose red cells do not sickle except for twice the frequency of significant bacteriuria. Thus, the only major cause for special concern by women with sickle cell trait who contemplate reproduction is their potential for transmission of one gene for sickling to the off spring.

A prospective study of angiotensin II pressor responsiveness in pregnancies complicated by chronic essential hypertension

The present study was designed to (1) outline, in a prospective manner, vascular responsiveness to angiotensin II (A-II) in gravidas with essential hypertension and (2) ascertain if increased sensitivity to infused A-II could be detected before worsening of hypertension developed in those women who were destined to develop superimposed pregnancy-induced hypertension (PIH). Sixty-three women with chronic essential hypertension were studied sequentially throughout pregnancy and two groups of patients were defined on the basis of clinical outcome and serial measurements of vascular reactivity to exogeneously administered A-II. The first group consisted of 29 gravidas with chronic hypertension alone and the second group was composed of 34 patients with chronic hypertension who were destined to develop superimposed PIH. Vascular resistance to infused A-II (more than 7 ng. per kilograms per minute required to increase diastolic blood pressure 20 mm. Hg) was observed from weeks 21 to 27 of gestation in both groups of patients. In the gravidas with essential hypertension alone, resistance to A-II persisted throughout the remainder of pregnancy. However, in those women destined to develop PIH, an increased sensitivity to A-II developed after week 27 of gestation and the differences in mean values between the two groups of patients became highly significant after week 30 of gestation (P less than 0.025). although individual determinations obtained in both groups of patients between weeks 28 and 32 of preganncy suggested that pressor responsiveness to A-II might be used as a screening technique to identify those women destined to develop PIH, additional studies conducted between weeks 28 and 32 of gestation will be required before the efficacy of such a screening technique is clearly established.

An analysis of the utility of plasma immunoreactive estrogen measurements in determining delivery time of gravidas with a fetus considered at high risk

Although maternal estrogen excretion and plasma estrogen levels are widely used to assess fetal health, the utility of these tests in lowering perinatal mortality rates has not been established. In order to ascertain if, with the help of plasma immunoreactive estrogen measurements, a reduction in perinatal deaths could be achieved, a population of women with a fetus at high risk were randomly divided into two groups and studied prospectively: in 315 gravidas, the estrogen results were reported (Group A); in 307, they were not reported (Group B). Nine perinatal deaths occurred in Group A, 10 in Group B. Ten Group B women whose infant ultimately did well would have been delivered 28 days or more prematurely if management had been based solely on the basis of abnormal immunoreactive estrogen levels. Measurement of estrogen levels is of little value in management of women with a fetus at risk; it may even lead to erroneous premature delivery.

Abortion complicated by clostridium perfringens infection

Abstract Abortion complicated by Clostridium perfringens sepsis and intense hemolysis , although rare, is a highly lethal disease. Hysterectomy to remove necrotic tissue, heparinization to prevent intravascular coagulation, exchange transfusion to remove irreversibly damaged red cells as well as circulating heme pigments, and hyperbaric oxygen have been suggested for treatment. To date, however, there is no convincing evidence that the benefits derived from these procedures outweight the risks inherent in their use. Infected abortion complicated by Clostridium perfringens bacteremia but without overt hemolysis is relatively common. In the absence of hemolysis, prompt administration of penicillin and tetracycline followed soon by curettage provides effective therapy with prompt recovery.

Measurements of menstrual blood loss

Menstrual blood loss in 21 apparently normal women (nurses student nurses and technicians) at Parkland Memorial Hospital was investigated for 54 cycles. 5 additional subjects who had heavy flows were also observed for 13 cycles. 10 to 14 days before expected menstruation 10 microcuries of radioactive iron ferrous citrate was administered intraveneously; the tampons and napkins were then collected in separate containers and analyzed for radioactivity using a well-type scintillation counter. The average blood loss per period among the 21 subjects was 25 ml; average duration of flow was 4 days; mean hematocrit determination was 42. average duration of flow was 5 days; mean hematocrit determination was 41. The amount of iron lost (in the form of hemoglobin) ranged from 5 to 26 mg. with an average of 12 mg./period. An ordinary diet should compensate for this iron loss. Among patients with excessive menstrual flow iron lost as hemoglobin was as high as 150 mg. in one patient. These findings indicate that women who have apparently normal flow actually lose very little blood and are aware of any appreciable change in the flow. Iron deficiency of women who are anemic pregnant or who have excessive blood loss during menstruation can be corrected by prescribing iron.

Maternal folate deficiency and pregnancy wastage: IV. Effects of folic acid supplements, anticonvulsants, and oral contraceptives

A group of studies on indigent hospital patients were conducted on the role of folate supplements, pregnancy and oral contraceptives in megaloblastic anemia. First 25 pregnant women, given 500 mg iron dextran and 30 mg folic acid for 2-3 months, had 12.4% hemoglogin at delivery, compared with 49 women given only iron who had 12.5% hemoglobin, and 49 untreated women who had 11.3% hemoglobin. Second, plasma folate levels in groups of pregnant women were compared: mean folate was 4.7 ng/ml in 82 normal women, 3.1 in 21 treated epileptics, and about 1.2 in 31 women with megaloblastic anemia. In 77 pregnancies in 43 epileptic women there were no reasons to blame low folate levels for pregnancy wastage since no abruptio placentae or bleeding occurred; and incidence of low birth weight, perinatal death, and prematurity was lower than in the general population. Third, the effect of oral contraceptives on folate levels was observed. Mean plasma folate levels were 8.1 ng/ml in 55 control women, 8.0 in 57 women using the pill, 4.7 in normal women in late pregnancy, and about 1.1 in pregnant women with megaloblastic anemia. Fourth, mean hemoglobin levels rose from 7.6 to 13.4 9m/100 ml within a few weeks in 5 women with gestational megaloblastic anemia after treatment with normal diet, without supplement, and oral contraceptives. One woman with puerperal megaloblastic anemia failed to respond to a regular diet while taking Ovulen, 6 tablets daily. The results suggest that plasma folate levels were neither lower in oral contracepting women nor did the pill prevent the increase in folate in megaloblastic anemia patients treated with diet. Thus the authors concluded that folate supplement is not needed for pill users.

Pressor responsiveness to angiotensin II in hospitalized primigravid women with pregnancy-induced hypertension

Hospitalization of women with pregnancy-induced hypertension is beneficial in improving pregnancy outcome, but how it affects this physiologic process is not clear. In the present investigation, we evaluated pressor responsiveness to angiotensin II in 62 hospitalized women with pregnancy-induced hypertension. Although each of the women became normotensive, at least transiently, all remained sensitive to the pressor effects of angiotensin II. Thus, the beneficial effect of hospitalization on women with pregnancy-induced hypertension cannot be attributed to a decrease in the responsiveness to the action of angiotensin II.

The influence of maternal folate and iron deficiencies on intrauterine life

An analysis of what is currently known about the role of maternal folate and iron deficiencies in pregnancy wastage, including abruptio placentae, fetal malformation, and abortion, is presented. Several observations are described which are not compatible with the concept that maternal folate or iron deficiency, per se, is of significance in the genesis of perinatal mortality or serious morbidity. The fetus and placenta quite effectively parasitize folate and iron from the mother even when she is grossly deficient in these nutrients.