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Biomedical subjects

W M Barron

Publications and source records attributed to W M Barron.

At least 19 recordsLinked to original sources
PubMed1999

Reducing unnecessary coagulation testing in hypertensive disorders of pregnancy.

OBJECTIVE: To estimate the magnitude of laboratory testing for hypertension in pregnancy and determine whether abnormalities in prothrombin time (PT), activated partial thromboplastin time (aPTT), and fibrinogen can be predicted by results of common, less expensive tests. MATERIALS AND METHODS: Laboratory records were searched and charts were reviewed to identify gravidas tested for hypertension and to exclude conditions producing coagulopathy. Contingency tables were constructed to assess the ability of the platelet count, lactate dehydrogenase, and transaminases to predict coagulation test results. RESULTS: Preliminary data on 73 gravidas found that a platelet count plus a lactate dehydrogenase test best predicted coagulation abnormalities. Results on another 732 gravidas indicated that coagulation tests were obtained in about 30%. No patient had a PT greater than 18 seconds, two had an aPTT greater than 40 seconds, and three had fibrinogen levels less than 200 mg/dL. The combination of a normal platelet count plus a normal lactate dehydrogenase had a negative predictive value of 100% for clinically significant abnormalities of PT and aPTT, and 99% for significant abnormalities of fibrinogen. CONCLUSIONS: Substantial coagulation testing was done on gravidas evaluated for a hypertensive disorder even though the prevalence of clinically significant abnormalities was low. Laboratory evaluation of patients suspected of having preeclampsia need not include a PT, aPTT, or fibrinogen test when there is no evidence of bleeding or of a condition that could produce coagulopathy and when the platelet count and lactate dehydrogenase level are both normal.

Blood Coagulation Tests↗
PubMed1995

Effect of oral protein loading on renal hemodynamics in human pregnancy.

Glomerular filtration rate (GFR) and ERPF increase approximately 50% in human pregnancy. To determine if pregnant women have additional "renal reserve," inulin and p-aminohippurate clearances (Cin, CPAH) were measured in maximally hydrated women before and after a 300-g steak meal, once during late gestation, and again > or = 3 mo postpartum. Protein loading increased Cin [106 +/- 5 (SE) to 119 +/- 4 ml/min, P < 0.003], but not CPAH (587 +/- 35 to 624 +/- 32 ml/min, NS) in the nonpregnant state, but neither clearance was altered during gestation (Cin: 156 +/- 7 to 160 +/- 9.6 ml/min, NS; CPAH: 831 +/- 36 to 899 +/- 37 ml/min, NS). A natriuresis occurred only postpartum (+142 mu eq/min, P < 0.02), which could be explained by the increased GFR alone, since indexes of filtrate delivery and reabsorption (V/GFR, CH2O/GFR, CH2O/V) and fractional sodium excretion changed little. Dopamine excretion, uninfluenced by protein, did not correlate with increments in GFR. A carbohydrate meal (time controls) had no effect on the above described parameters. We make the following conclusions. If protein and pregnancy achieve hyperfiltration by similar mechanisms, these pathways appear "exhausted" in gestation. Also, oral protein loading does not measure maximal renal reserve, since basal GFR in late gestation was substantially greater than that measured after protein feeding in nonpregnant subjects.

Adult↗
PubMed1994

Effect of autonomic blockade on pressor responses to vasopressin in pregnant rats.

OBJECTIVE: We tested the hypothesis that gestational changes in reflex neural control of the heart and vasculature contribute to altered cardiovascular responses to vasopressin during pregnancy. STUDY DESIGN: Changes in mean arterial pressure, cardiac output, total peripheral resistance, and heart rate were measured in response to constant infusion of arginine vasopressin (0.15 to 2.5 mU/kg/min) in conscious pregnant and virgin rats (n = 9) with total autonomic blockade plus restoration of baseline hemodynamics by norepinephrine infusion. RESULTS: Resting cardiac output was 40% higher and total peripheral resistance 30% lower in pregnant animals (p < 0.01). Constant infusion of arginine vasopressin evoked equivalent changes in mean arterial pressure in both groups, but the respective contributions of cardiac output and total peripheral resistance to mean arterial pressure differed between groups. Cardiac output was unchanged and the increase in total peripheral resistance was significantly blunted in pregnant vs virgin rats during arginine vasopressin infusion. Control data in nonblocked revealed similar pressor responses to arginine vasopressin in gravid compared with virgin rats but no differences in the contributions of cardiac output and total peripheral resistance to the change in mean arterial pressure. CONCLUSION: These findings suggest that neural modulation of arginine vasopressin-induced hypertension is altered during pregnancy and are consistent with a reduction in intrinsic vascular sensitivity to arginine vasopressin during gestation.

Animals↗
PubMed1993

Total autonomic blockade eliminates the attenuated pressor response to angiotensin II in pregnant rats.

Pressor responses to angiotensin II (ANG II) are markedly attenuated in reflex-intact pregnant animals, a phenomenon widely attributed to intrinsic changes in vascular reactivity. To test the hypothesis that gestational augmentation of neural reflex activity contributes importantly to this phenomenon, changes in mean arterial pressure (MAP), cardiac output (CO), and total peripheral resistance (TPR) were compared during constant infusion (25-400 ng.kg-1.min-1) of ANG II in conscious virgin and pregnant rats, using a model of total autonomic blockade (chlorisondamine chloride and methscopolamine bromide), with restoration of baseline hemodynamics by infusion of norepinephrine. Basal CO was higher and TPR lower in pregnant (CO 121.8 +/- 3.8 ml/min; TPR 0.78 +/- 0.04 mmHg.ml-1.min) compared with virgin (CO 95.9 +/- 3.9 ml/min; TPR 1.05 +/- 0.08 mmHg.ml-1.min) rats (P < 0.005). Pressor responses to ANG II were similar in both groups of reflex-blocked animals due to comparable changes in TPR and CO (not significant by repeated-measures analysis of variance). Other experiments demonstrated that changes in MAP after bolus administration of ANG II did not differ in areflexic virgin and gravid rats. Thus in the absence of autonomic control ANG II has similar effects on systemic resistance in pregnant and nonpregnant rats, suggesting that reflex neural mechanisms contribute significantly to gestational changes in pressor responsiveness. These data further suggest that pregnancy is not accompanied by a generalized decrease in vascular reactivity to all pressor agents.

Angiotensin II↗
PubMed1993

Metabolic clearance of vasopressin and an analogue resistant to vasopressinase in human pregnancy.

The metabolic clearance rate (MCR) of arginine vasopressin (AVP) increases fourfold during human pregnancy. To explore whether circulating vasopressinase may play a role in this change, six women underwent a three-tier infusion clearance study, twice, in random order, to determine the MCRs of either AVP or 1-deamino-8-D-AVP (dDAVP, an analogue resistant to degradation by vasopressinase). Volunteers were tested in late pregnancy (LP), 24-48 h postdelivery (PD), and 5-6 (PP1) and 10-12 (PP2) wk postpartum, thus examining MCRs when vasopressinase levels were high, before and after removal of the placenta (LP and PD), and when plasma enzyme activity was becoming (PP1) and became (PP2) undetectable. Manipulation of infusate permitted comparison of MCRs at three plasma levels whose range was similar at each test period. PAVP and PdDAVP (2.2 and 10 pg/ml, respectively, during the initial infusion) increased to 8 and 31 pg/ml, stepwise increments that had no influence on respective MCRs (AVP: 3.4, 2.2, 0.77, and 0.67 l/min during LP, PD, PP1, and PP2 compared with 0.18, 0.21, 0.17, and 0.15 l/min for dDAVP). Comparison of similar and submaximal urinary osmolality revealed PdDAVP values three- to fourfold greater than PAVP. Von Willebrand factor (VWF) and factor VIIIc levels increased almost fourfold in response to dDAVP during pregnancy, but only doubled in the nonpregnant state; these differences did not reach significance. We conclude that although AVP disposal rates increase fourfold in pregnancy, those of dDAVP change little, suggesting a role of vasopressinase in the increased MCR of AVP in gestation (as well as in the genesis of certain polyuric disorders of pregnancy).(ABSTRACT TRUNCATED AT 250 WORDS)

Arginine Vasopressin↗
PubMed1993

Prior feeding alters the response to the 50-g glucose challenge test in pregnancy. The Staub-Traugott effect revisited.

OBJECTIVE: To examine the effect of prior meal ingestion on the glucose, insulin, and C-peptide response to a 50-g glucose challenge test in the third trimester of pregnancy. RESEARCH DESIGN AND METHODS: Ten pregnant women with gestational diabetes mellitus and 12 nondiabetic pregnant control subjects matched for age and weight underwent a 50-g glucose challenge test on three occasions within a 2-wk period, in random order. On one occasion the test was administered in the fasting state (fasting glucose challenge test), on a second occasion the test was administered 1 h after ingestion of a standard mixed meal (1-h postprandial study), and on a third occasion the test was administered 2 h after ingestion of a standard mixed meal (2-h postprandial study). RESULTS: In the control subjects, the plasma glucose level 1 h after ingestion of 50 g of glucose was higher in the fasting study (7.8 +/- 0.4 mM, 7 of 12 subjects with glucose > or = 7.8 mM) than in the 1-h postprandial study (6.7 +/- 0.3 mM, 3 of 12 subjects with glucose > or = 7.8 mM) and the 2-h postprandial study of (6.3 +/- 0.4 mM, 3 of 12 with glucose > or = 7.8 mM) (P < 0.01). In the postprandial studies of control subjects, insulin and C-peptide levels were higher at the time of ingestion of the 50 g of glucose, but the early (1 h) insulin secretory response was less than in the fasting study. In the diabetic patients, glucose levels 1 h after 50-g glucose ingestion were similar in the fasting study (10.5 +/- 0.4 mM, no subjects with glucose value < 7.8 mM) and the 1-h postprandial study (11.0 +/- 0.6 mM, 1 subject with glucose < 7.8 mM), but was lower in the 2-h postprandial study (9.3 +/- 0.3 mM, 1 subject with glucose < 7.8 mM) (P < 0.03). In contrast to the control subjects, the insulin secretory response to 50 g of oral glucose was greater in the two postprandial studies than in the fasting study. CONCLUSIONS: We have reached the following conclusions. 1) In nondiabetic gravidas, plasma glucose concentrations 1 h after ingestion of a 50-g oral glucose load are higher if administered in the fasting state compared with the postprandial state. 2) During normal pregnancy the Staub-Traugott Effect, i.e., improved glucose disposal after successive glucose load administrations, occurs and appears to be caused by mechanisms other than enhanced insulin secretion with successive glucose loads. 3) The effect of the prandial state on plasma glucose response to the 50-g glucose challenge test used to screen for gestational diabetes mellitus may be of sufficient magnitude to significantly alter the operating characteristics, i.e., sensitivity and specificity, of this test.

Adult↗
PubMed1992

Indirect blood pressure measurement in pregnancy: Korotkoff phase 4 versus phase 5.

Controversy exists regarding which Korotkoff phase should be used to estimate diastolic blood pressure during pregnancy, some authorities recommending phase 5 (disappearance of sounds) and others suggesting phase 4 (muffling). Available data indicate that Korotkoff phase 5 more closely approximates true intraarterial diastolic pressure in pregnant women. Nonetheless, it has been suggested that phase 5 is unmeasurable in a significant number of gravid women, making this end point less desirable. However, studies examining this issue indicate that Korotkoff phase 5 is determinable in more than 90% of gravid women and that the incidence of an indeterminable phase 4 is at least as great as that for phase 5. Moreover, there appears to be greater observer variability in the measurement of phase 4 compared with phase 5. We conclude that available evidence supports recommendations for the use of Korotkoff phase 5 as the preferred end point to estimate diastolic blood pressure during pregnancy. In those few patients having very low or indeterminate phase 5 determinations, both phase 4 and phase 5 should be recorded and the former used to guide patient management. An alternative strategy is to record both phases in all gravid women beginning at the first prenatal visit so that baseline phase 4 values are available in the event that phase 5 becomes indeterminate.

Blood Pressure Determination↗
PubMed1992

Effect of sinoaortic denervation on pressor responses in pregnant rats.

We tested the hypothesis that augmented arterial baroreflex activity contributes to attenuation of pressor responses in intact pregnant animals by comparing changes in blood pressure and heart rate during infusions of angiotensin II, phenylephrine, and vasopressin in chronically instrumented pregnant and virgin rats approximately 5 wk after sinoaortic denervation (SAD) or sham surgery. Baseline mean arterial pressure was significantly lower in pregnant animals in both the sham-operated (pregnant 91.7 +/- 1.7 mmHg, virgin 103.7 +/- 2.5 mmHg) and SAD states (pregnant 107.3 +/- 4.0 mmHg, virgin 114.1 +/- 4.0 mmHg). Pressor responses to all three agents were significantly blunted in pregnant animals compared with similarly treated virgins, with the magnitude of attenuation similar in both sham and SAD states. Heart rate decreased similarly in reflex-intact pregnant and virgin animals during pressor infusions. These findings suggest that attenuated pressor responses in the pregnant rat are due primarily to mechanisms other than augmentation of arterial baroreflex activity and are consistent with a generalized reduction in vascular sensitivity during gestation.

Angiotensin II↗
PubMed1992

The syndrome of preeclampsia.

Preeclampsia has traditionally been viewed as one of several forms of hypertension complicating pregnancy. More recently, the multisystem nature of this unique gestational disorder has been emphasized. Pathophysiologic events, including abnormal placentation and heightened vascular reactivity, may occur weeks or months prior to clinical recognition of the disease. Although most frequently presenting as hypertension and proteinuria, hepatic (abdominal pain and elevation of transaminases) and hematologic (intravascular hemolysis and thrombocytopenia) involvement may be important features of the disease. Current theories suggest that multiorgan dysfunction may be caused by widespread vascular endothelial dysfunction, vasospasm, and variable activation of coagulation mechanisms. Pending delivery, which is the only definitive therapy for preeclampsia, maternal complications of intracerebral hemorrhage and eclampsia may be prevented with judicious use of antihypertensive medication (e.g., hydralazine) and magnesium sulfate, respectively. Finally, data from a number of small trials suggest that low-dose aspirin (60-100 mg/d) may reduce the incidence of preeclampsia in patients at high risk without adversely affecting the fetus or newborn; however, it is recommended that aspirin not be used as a routine prophylactic intervention until publication of results of several ongoing large multicenter trials, which will help to more fully clarify the benefits and risks of this approach.

Blood Pressure↗
PubMed1991

Osmotic and volume control of vasopressin release in pregnancy.

This article, a review of factors controlling vasopressin (AVP) release in pregnancy, extends our contribution to a symposium in this journal published in 1987 (vol X, pp 270-275). Body tonicity decreases (approximately 10 mOsm/kg) very early in pregnancy due to decrements in the osmotic thresholds for AVP release and thirst. In addition, the metabolic clearance rate (MCR) of AVP markedly increases between gestational week 10 and midpregnancy, and is paralleled by the appearance and increase of circulating cystine aminopeptidase (vasopressinase), while the MCR of 1-deamino-8-D-AVP (DDAVP), an analogue resistant to inactivation by the enzyme, changes little in pregnancy. These increases (MCR of AVP and plasma vasopressinase) may explain certain syndromes of transient diabetes insipidus (DI) that complicate gestation. Finally, mechanisms responsible for the altered osmoregulation in pregnancy are obscure, but chorionic gonadotropin may be involved in the changes during human gestation.

Animals↗
PubMed1990

Regulation of blood pressure in pregnancy: pressor system blockade and stimulation.

Contributions of the autonomic nervous system (ANS), renin-angiotensin system (RAS), and arginine vasopressin (AVP) to basal mean arterial pressure (MAP) were evaluated in near-term pregnant and virgin rats as follows. MAP and heart rate (HR) were measured before and after ganglionic, alpha-adrenoreceptor, RAS, and/or AVP blockade. In addition, pressor responses to angiotensin II (ANG II), norepinephrine, phenylephrine, or AVP were determined in ganglionic-blocked animals. In both groups decrements in MAP were greatest after ganglionic or alpha-blockade, intermediate after RAS blockade, and negligible after AVP-V1 antagonism ([d(CH2)5Tyr(Me)]AVP). Recovery of MAP was also similar in the two groups except after phentolamine when MAP and HR remained lower in gravid rats. Superimposition of RAS or AVP blockade during phentolamine infusion suggested that ANG II and AVP were less effective in supporting MAP during alpha-blockade in pregnancy. Pressor responses to ANG II and norepinephrine during ganglionic blockade were markedly blunted during pregnancy; however, those to phenylephrine and AVP were unchanged. We conclude that contributions of ANS, RAS, and AVP to basal MAP are similar in pregnant and virgin rats; neural mechanisms dominating in both groups. However, recovery during alpha-blockade is impaired during gestation, apparently due to blunted HR responses and decreased pressor contributions of ANG II and AVP. This may be explained, in part, by decreased vascular reactivity to ANG II, although a similar mechanism cannot be invoked for AVP.

Adrenergic alpha-Antagonists↗
PubMed1990

Pressor effect of endothelium-derived relaxing factor inhibition in conscious virgin and gravid rats.

We used pressor responses to N-methylarginine (NMA), a specific inhibitor of endothelium-derived relaxing factor (EDRF) biosynthesis, to assess the contribution of EDRF to control of basal blood pressure in conscious, chronically instrumented virgin and gravid rats. Hypotheses were that NMA would raise blood pressure in conscious animals in spite of intact cardiovascular reflexes and that differing effects in virgin and pregnant animals would reveal contributions of EDRF to the physiological vasodilation of pregnancy. Basal mean arterial pressure (MAP) and heart rate (HR) were 106 +/- 12 mmHg and 394 +/- 27 beats/min (n = 31) in virgin and 102 +/- 8 mmHg and 378 +/- 18 beats/min (n = 14) in gravid rats. After NMA (150 mg/kg iv), increments in MAP and decreases in HR were similar in each group (virgin, delta MAP = 38 +/- 12 mmHg, delta HR = -65 +/- 27 beats/min, n = 14; gravid, delta MAP = 33 +/- 8 mmHg, delta HR = -63 +/- 20 beats/min, n = 6). Pretreatment with excess L-arginine reduced pressor responses to NMA by 80% in both pregnant and virgin animals. In contrast, L-arginine had no significant effect on the pressor response to phenylephrine (6.4 mg/kg iv). EDRF contributes importantly to regulation of basal blood pressure in conscious animals, and pregnancy does not alter the pressor effect of EDRF inhibition in the rat.

Animals↗
PubMed1989

Role of hemodynamic factors in osmoregulatory alterations of rat pregnancy.

Plasma osmolality (Posmol) decreases in pregnancy, possibly because of hemodynamically mediated arginine vasopressin (AVP) secretion, i.e., inadequate vascular filling and/or decreased blood pressure. This hypothesis was tested in Sprague-Dawley rats treated on gestational days 1-18 or 13-18 with 1) deoxycorticosterone acetate (DOCA) + standard chow (0.5% Na), 2) vehicle + standard chow, or 3) high-Na (1.25%) diet. Renal sodium "escape" and suppression of the renin-aldosterone system suggested "effective volume expansion," yet Posmol was similar in all pregnant groups, 7-10 mosmol/kg below levels in virgin controls, and plasma AVP was unaltered. Apparent osmotic thresholds for AVP secretion, similar in control and DOCA-treated gravid animals, were 8-10 mosmol/kg below those of untreated virgin rats. Norepinephrine + DOCA, administered to gravid animals consuming normal or high-Na chow, increased blood pressure approximately 10% above control levels, but this also failed to alter Posmol. These data suggest that mechanisms other than hemodynamically mediated AVP secretion are responsible for the osmoregulatory alterations accompanying rodent pregnancy.

Animals↗
PubMed1989

Osmoregulation of thirst and vasopressin release in pregnancy.

Osmoregulation is altered in human gestation, body tonicity declining to a nadir early in pregnancy after which a new steady-state plasma osmolality is maintained until term. Development of precise, sensitive, and specific radioimmunoassays for arginine vasopressin (AVP), which permit clearer definitions of functional properties of the osmoregulatory system, have led to a formulation of how these changes occur (both in women as well as in a gravid rat model). The osmotic thresholds for thirst and antidiuretic hormone release each decrease approximately 10 mosmol/kg during the initial weeks of human gestation. Lowering the threshold to drink stimulates increased water intake and dilution of body fluids. Because AVP release is not suppressed at the usual levels of tonicity, it still circulates and water is retained. Osmolality declines until it decreases below the osmotic thirst threshold (situated several mosmol/kg above that for hormone secretion), and a new steady state, with little change in water turnover, is established. The metabolic clearance rate of AVP is also altered, increasing three- to fourfold between gestational week 10 and midtrimester, paralleling the appearance and rapid rise in circulating cystine-aminopeptidase (vasopressinase), an observation that may explain several disorders of water handling that complicate human pregnancy. Finally, mechanisms responsible for the altered osmoregulation are obscure but chorionic gonadotropin may be involved in the changes during human gestation.

Animals↗