pituitrin and Fetal-Hypoxia

Topics: Adrenocorticotropic Hormone; Animals; Blood Pressure; Chronic Disease; Disease Models, Animal; Epinephrine; Fatty Acids, Nonesterified; Female; Fetal Heart; Fetal Hypoxia; Glucagon; Glycogen; Heart Rate; Lactates; Norepinephrine; Pregnancy; Propranolol; Regional Blood Flow; Sheep; Vasopressins

Sensitive biomarkers are needed to rapidly identify high-risk infants after hypoxia-ischemia for neuroprotective treatment. Hypotension is a key determinant of hypoxic-ischemic neural injury, and a potent stimulus of humoral pressors including angiotensin-II and arginine vasopressin. We therefore aimed to quantify the relationship between vasopressin and angiotensin-II levels in the latent phase after hypoxia-ischemia induced by umbilical cord occlusion (UCO) with both the severity of preceding hypotension and subsequent neuronal injury.. Chronically instrumented near-term fetal sheep underwent sham-UCO or UCO for either 15 min or until mean arterial pressure was <8 mmHg. Neuronal injury was assessed after 72 h recovery.. Umbilical cord occlusion was associated with severe hypotension that recovered after UCO; two fetuses developed profound secondary hypotension within 6 h and died. Vasopressin levels but not angiotensin-II were significantly elevated 1-3 h after UCO and were closely associated with the severity of hypotension during UCO and the subsequent severity of neuronal loss in the parasagittal and lateral cortex, caudate nucleus and putamen. The Youden cut-point for vasopressin at 1 h was 180.0 pmol/L, with sensitivity 100% and specificity 92.3% for severe neuronal injury or death.. Vasopressin levels shortly after moderate-severe hypoxia-ischemia may be a useful early biomarker to guide the timely implementation of neuroprotective treatment.. It can be difficuIt to rapidly identify infants who might benefit from therapeutic hypothermia. We investigated whether increases in plasma pressor hormones early after hypoxia-ischemia were biomarkers for neonatal hypoxic-ischemic encephalopathy using near-term fetal sheep. Arginine vasopressin levels were elevated at 1-3 h after hypoxia-ischemia and were predictive of the severity of preceding hypotension and subsequent risk of severe neuronal injury or death after hypoxia-ischemia. Arginine vasopressin may help identify neonates at high risk of hypoxic-ischemic encephalopathy early within the therapeutic window for hypothermia.

Topics: Angiotensin II; Animals; Arginine Vasopressin; Biomarkers; Blood Gas Analysis; Disease Models, Animal; Female; Fetal Hypoxia; Hydrogen-Ion Concentration; Hypotension; Hypoxia-Ischemia, Brain; Male; Nervous System Diseases; Neurons; Sheep; Umbilical Cord; Vasopressins

To measure the umbilical plasma concentration of endothelin (ET)-1 in the presence of labor, fetal heart rate (FHR) abnormalities, and fetal hypoxia.. Umbilical and maternal plasma concentrations of ET-1 were measured in 100 pregnant women at full-term deliveries (60 with vaginal delivery without induction and 40 with elective cesarean delivery without labor). We assessed the FHR pattern, measured umbilical blood gases and plasma concentration of vasopressin, and investigated the relationships between the umbilical vein-artery ET-1 concentration difference and these variables.. The concentration of ET-1 in the umbilical vein was higher than in the umbilical artery and the maternal vein in all cases. The umbilical vein-artery ET-1 concentration difference (mean +/- standard error of the mean) was significantly greater in the vaginal delivery group (4.5 +/- 2.0 pmol/L) than in those delivered by elective cesarean (1.7 +/- 1.5 pmol/L) (P < .05). The umbilical vein-artery ET-1 concentration difference was significantly greater when more than three episodes of severe variable decelerations occurred during the 30-minute period before delivery (7.0 +/- 2.0 pmol/L) than in the absence of any decelerations (1.6 +/- 1.5 pmol/L) (P < .05). The umbilical vein-artery ET-1 concentration difference correlated positively with the umbilical arterial concentration of vasopressin (r = 0.45, P < .05) and negatively with the umbilical arterial oxygen pressure (r = -0.47, P < .05).. In cases of vaginal delivery with FHR abnormalities and with fetal hypoxia, the fetoplacental concentration of ET-1 was increased.

Topics: Adult; Cesarean Section; Delivery, Obstetric; Endothelins; Female; Fetal Blood; Fetal Hypoxia; Heart Rate, Fetal; Humans; Labor, Obstetric; Oxygen; Pregnancy; Vasopressins

The present study was designed to test the hypothesis that arginine vasopressin mediates the fetal cardiovascular response to acute hypoxia. Chronically catheterized sheep fetuses at 126 to 138 days' gestation were infused with either an arginine vasopressin pressor antagonist (n = 8) or saline solution as control (n = 8). A 30-minute hypoxia was induced by infusion of nitrogen containing 5% carbon dioxide into the maternal trachea. Fetal arterial PO2 decreased 13.1 +/- 1.3 (SE) mm Hg from a basal value of 23.8 +/- 1.5 mm Hg and there was no significant difference in the degree of hypoxia between the two groups. Fetal arterial and venous pressures increased significantly, whereas the blood volume decreased, but these changes were similar between the control and arginine vasopressin-blocked fetuses. Heart rate fell similarly in both groups during hypoxia by an average of 35 beats/min. At the termination of hypoxia, heart rate in the blocked group rebounded to levels significantly above baseline and remained elevated for 30 minutes, whereas heart rate in the control group returned slowly to basal values. Recovery of arterial pressure, venous pressure, and blood volume were similar in the two groups. Thus it appears that arginine vasopressin may mediate in part the fetal heart rate response to acute hypoxia. However, the blood volume, arterial pressure, and venous pressure responses to hypoxia appear to be induced by factors other than arginine vasopressin.

Topics: Animals; Arginine Vasopressin; Blood Pressure; Carbon Dioxide; Cardiovascular System; Female; Fetal Hypoxia; Gestational Age; Heart Rate, Fetal; Hydrogen-Ion Concentration; Oxygen; Pregnancy; Radioimmunoassay; Sheep; Vasopressins; Venous Pressure

The effects of inadequate expansion of maternal blood volume on uterine blood flow, fetal oxygen levels and vasoactive mediators during the third trimester were studied in 8 pregnant sheep. Results were compared to those obtained during 15 normal pregnancies. Prevention of the normal (20 ml/day) increase in maternal plasma volume was achieved by repeated haemorrhage and injections of furosemide. These treatments also reduced the rise in blood flow to the pregnant uterine horn that normally occurs during this period of gestation: at term flow was only 508 +/- 61 (SEM) compared to 838 +/- 83 ml/min in the control group (P greater than 0.01). This reduction in uterine blood flow caused a gradual fall in fetal PaO2, and rise in fetal levels of plasma renin activity, vasopressin, catecholamines and angiotensin II without change in pHa or base excess. Four to 5 days prior to delivery, the difference from control in PaO2 was -3.9 +/- 0.5 mmHg, plasma renin activity +2.9 +/- 1.7 ng/ml.h, vasopressin +4.2 +/- 1.1 pg/ml, catecholamines +957 +/- 145.3 pg/ml and angiotensin II +243 +/- 108.2 pg/ml. Furthermore, the fall in PaO2 and rise in vasoactive mediators that normally occur 3-5 days prior to the onset of labour was either absent (PaO2 and plasma renin activity) or blunted. Thus when expansion of blood volume during pregnancy is inadequate, blood flow to the uterus is adversely affected. This leads to various degrees of chronic fetal hypoxaemia and stimulation of vasoactive mediator systems. However, the normal stimulation of vasoactive mediator systems that occurs 3-5 days before delivery appears to be blunted. Experimental prevention of blood volume expansion during pregnancy produces an excellent model for the study of chronic mild fetal hypoxaemia.

Topics: Angiotensin II; Animals; Blood Pressure; Bloodletting; Catecholamines; Disease Models, Animal; Female; Fetal Blood; Fetal Hypoxia; Furosemide; Heart Rate, Fetal; Hydrogen-Ion Concentration; Oxygen; Plasma Volume; Pregnancy; Regional Blood Flow; Renin; Sheep; Uterus; Vasopressins

The concentrations of vasopressin in the plasma and cerebrospinal fluid (CSF) of the chronically catheterized fetal lamb were measured under basal and hypoxic conditions. Under basal conditions, samples were obtained from 13 fetal lambs of 117-146 days gestation. The mean +/- SEM vasopressin level in CSF was 19.5 +/- 1.5 pg/ml; the mean plasma vasopressin level of 1.9 +/- 0.2 pg/ml was significantly less (P less than 0.001). No consistent change in concentrations of vasopressin in CSF was observed with gestational maturation in 3 animals sampled sequentially or in individual samples obtained over the last 32 days of gestation. The mean vasopressin concentration in the CSF of the pregnant ewe was 5.1 +/- 0.4 pg/ml. The gradients for osmolality, sodium, and potassium between fetal plasma and CSF were: osmolality, 298.4 +/- 1.6 to 304.3 +/- 1.4 mosmol/kg; sodium, 140.9 +/- 0.5-142.5 +/- 0.5 meq/liter; and potassium, 4.3 +/- 0.1 to 3.3 +/- 0.1 meq/liter. Fetal hypoxia was induced by exposure of the ewe to 10% O2 in N2 for 30 min. The concentration of vasopressin increased from 1.7 +/- 0.3 to 277 +/- 144 pg/ml (P less than 0.001) in fetal plasma and from 21.4 +/- 3.8 to 47.1 +/- 9.9 pg/ml (P less than 0.04) in fetal CSF. When the ewe was exposed to room air under comparable experimental conditions, no similar changes in plasma or CSF vasopressin levels were observed in the fetus. Infusion of vasopressin into the fetal jugular vein at 1.0 mU/min for 30 min increased plasma concentrations from 2.3 +/- 0.5 to 83 +/- 17 pg/ml, while the CSF vasopressin values were 31.9 +/- 5.9 (basally) and 30.7 +/- 4.8 pg/ml (after infusion). Mean plasma and CSF osmolality, sodium, and potassium were not changed by any of these experimental interventions. We conclude that 1) under basal conditions, high concentrations of vasopressin are present in the CSF of the fetal lamb, the blood-CSF barrier appears to be impermeable to vasopressin, and concentrations of the hormone in fetal plasma are less than those in CSF; and 2) hypoxia is a potent stimulus of vasopressin release in both fetal plasma and CSF. The route of vasopressin released into the fetal CSF may be distinct from that released into plasma.

Topics: Animals; Blood Pressure; Blood-Brain Barrier; Female; Fetal Hypoxia; Gestational Age; Heart Rate; Pregnancy; Reference Values; Sheep; Vasopressins

Hypoxia is a potent stimulus to the release of vasopressin in fetal sheep, and plasma concentrations of the hormone correlate inversely with fetal oxygenation. Since the fetal kidney contributes to vasopressin clearance, we propose that measurement of increased amounts of vasopressin in amniotic fluid would be indicative of fetal hypoxia. Therefore, we measured concentrations of vasopressin in amniotic fluid under resting conditions, during and after fetal hypoxia, and with intravenous and intra-amniotic administration of vasopressin in 15 chronically instrumented fetal lambs between 111 and 141 days gestation. In the resting state, mean (+/- SE) vasopressin concentrations in amniotic fluid (1.6 +/- 0.3 pg ml-1) did not differ from those in maternal (1.4 +/- 0.4 pg ml-1) or fetal (1.8 +/- 0.2 pg ml-1) plasma. Following exposure of the ewe to 10% O2 or partial occlusion of the umbilical cord, vasopressin concentrations in fetal plasma increased significantly (P less than 0.001) to 200 +/- 59 pg ml-1 with a delayed increase in amniotic fluid concentrations (P less than 0.03) to 15.8 +/- 4.5 pg ml-1. This rise in concentration of vasopressin in amniotic fluid was sustained for at least 24 h and levels at that time were highly correlated with peak plasma concentrations (r = 0.83; P less than 0.001). Intravenous infusion of vasopressin into the fetus was accompanied by an equally significant (P less than 0.02) and sustained increase of vasopressin in amniotic fluid. Following intra-amniotic injection of vasopressin, levels remained increased for at least 24 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Amniotic Fluid; Animals; Female; Fetal Hypoxia; Fetus; Pregnancy; Pressure; Radioimmunoassay; Sheep; Time Factors; Uterus; Vasopressins

The factors associated with increased renal excretion of vasopressin (VP) were examined in the hypoxic fetus and newborn. Studies were conducted on six chronically instrumented fetal (117-136 days gestation) and seven newborn lambs (2-6-day-old). Hypoxia was produced by administration of 10% oxygen to the ewe or neonate for 30 min. This procedure caused a 50% reduction in PaO2, no significant change in pHa in either fetus or neonate and a slight fall in PaCO2. Hypoxia caused an increase in VP concentrations in plasma from 1.3 +/- 0.53 to 46.4 +/- 4.71 pg/ml in the fetus and from 5.9 +/- 2.80 to 50.2 +/- 26.68 pg/ml in the neonate. After hypoxia there was a fall in urine output from 0.27 +/- 0.045 to 0.17 +/- 0.046 ml/(min X kg) in the fetus and from 0.15 +/- 0.033 to 0.09 +/- 0.022 ml/(min X kg) in the newborn. The corresponding values for urine osmolality were the following: 168 +/- 30.8 to 325 +/- 30.6 mOsm/kg in the fetus and 388 +/- 65.4 to 523 +/- 51.8 mOsm/kg in the newborn. VP concentration in urine increased from 13 +/- 9.4 to a maximum of 176 +/- 32.4 pg/ml after 30 min of recovery in the fetus and 39 +/- 4.6 to 278 +/- 132.5 pg/ml after 1 h of recovery in the newborn. These levels remained high for at least 1 h after the end of hypoxia. There was a good linear correlation between plasma VP levels and the corresponding urine levels and excretion rates in both the fetus and newborn.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Animals, Newborn; Female; Fetal Hypoxia; Glomerular Filtration Rate; Hypoxia; Kidney Concentrating Ability; Natriuresis; Pregnancy; Sheep; Vasopressins

Hypoxia is a potent stimulus to the release of vasopressin in fetal sheep and, in turn, plasma concentrations of the hormone correlate inversely with fetal oxygenation. Because the fetal kidney contributes to vasopressin clearance, we propose that measurement of increased amounts of vasopressin in amniotic fluid would be indicative of fetal hypoxia. We therefore measured concentrations of vasopressin in amniotic fluid under resting conditions, during and after fetal hypoxia, and with intravenous and intra-amniotic administration of vasopressin in 15 chronically instrumented fetal lambs 111-141 d gestation. In the resting state mean (+/- SE) vasopressin concentrations in amniotic fluid (1.6 +/- 0.3 pg . ml-1) did not differ from those in maternal (1.4 +/- 0.4 pg . ml-1) or fetal (1.8 +/- 0.2 pg . ml-1) plasma. After exposure of the ewe to 10% O2 or partial occlusion of the umbilical cord, vasopressin concentrations in fetal plasma increased significantly (P less than 0.001) to 200 +/- 59 pg . ml-1 with a delayed increase in amniotic fluid concentrations (P less than 0.03) to 15.8 +/- 4.5 pg . ml-1. This rise in concentration of vasopressin in amniotic fluid was sustained for at least 24 h and levels at that time were highly correlated with peak plasma concentrations (r = 0.83, P less than 0.001). Intravenous infusion of vasopressin into the fetus was accompanied by an equally significant (P less than 0.02) and sustained increase of vasopressin in amniotic fluid. After intraamniotic injection of vasopressin, levels remained increased for at least 24 h.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Amniotic Fluid; Animals; Female; Fetal Hypoxia; Fetus; Maternal-Fetal Exchange; Meconium; Pregnancy; Radioimmunoassay; Sheep; Time Factors; Vasopressins

To investigate the developmental changes in the secretion of vasopressin and the potential role of beta-endorphin as a stimulus to the release of vasopressin, the concentrations of these peptides were measured in fetal, newborn, and adult sheep after episodes of induced hypoxia. The studies confirm that hypoxia is a potent stimulus to the release of both vasopressin and beta-endorphin in the fetal animal. In both the newborn lamb and the ewe, more profound hypoxia is necessary for a similar release. In the fetus, the release of both vasopressin and beta-endorphin after hypoxia increased with gestational maturation. A comparison of control concentrations of both peptides, the discordance of release in the newborn lamb, and the absence of a change in concentrations of vasopressin with infusion of beta-endorphin implies that these hormones are released in parallel but independently during hypoxic stress.

Topics: Aging; Animals; beta-Endorphin; Endorphins; Female; Fetal Hypoxia; Fetus; Hypoxia; Oxygen; Pregnancy; Radioimmunoassay; Sheep; Vasopressins

The renal response of the fetal lamb to repeated complete occlusion of the umbilical cord was studied in nine chronically instrumented animals. Five episodes of occlusion of the umbilical cord, each lasting for two minutes, produced a twofold rise in fetal urine osmolality and sodium, chloride, and potassium concentrations. Output of urine and glomerular filtration rate remained essentially unchanged while free water clearance decreased from a control of +0.10 to -0.02 ml. per kilogram per minute at the end of the fifth episode. Electrolyte concentrations in urine remained elevated for at least two hours following the occlusions. In addition to changes in urine composition, there was a 50- to 200-fold increase in the fetal plasma concentration of vasopressin. These studies indicate that complete interruption of the umbilical circulation, even though of short duration, produces disturbances in fetal renal function that can lead to loss of electrolytes in the urine. They provide an explanation for the low sodium levels reported in asphyxiated newborn infants in renal failure.

Topics: Acid-Base Equilibrium; Acidosis; Animals; Blood; Blood Pressure; Carbon Dioxide; Constriction; Electrolytes; Female; Fetal Diseases; Fetal Hypoxia; Fetus; Glomerular Filtration Rate; Heart Rate; Hydrogen-Ion Concentration; Kidney; Osmolar Concentration; Oxygen; Pregnancy; Sheep; Umbilical Cord; Urine; Vasopressins