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Biomedical subjects

J Itskovitz

Publications and source records attributed to J Itskovitz.

At least 55 records · Page 3Linked to original sources
PubMed1987

Ovarian prorenin.

We review here recent evidence that the ovaries synthesize and secrete prorenin and we explore the possible reasons why prorenin, and not active renin, is formed almost exclusively in this extra-renal site. Very high concentrations of prorenin are present in the human ovary in the fluid inside mature follicles. This ovarian prorenin appears to be secreted into the circulation since plasma prorenin increases in normal women for two to three days at mid-menstrual cycle, at the time of ovulation. No change in plasma active renin occurs at this time. Plasma prorenin increases much more at mid-cycle in women whose ovaries have been hyperstimulated with gonadotropins. Their mid-cycle increment in plasma prorenin (after hCG) is directly related to the number of ovarian follicles. Plasma prorenin also increases markedly (10-fold) in pregnant women within two weeks after conception, in parallel with the rise in endogenous hCG. The ovaries are the apparent source of the increase in plasma prorenin during pregnancy since no such increase occurred in a woman with ovarian failure who conceived after receiving a donor egg. These results suggest that the ovaries synthesize and secrete prorenin in response to stimulation by gonadotropic hormones. Future studies will investigate the potential role of ovarian prorenin in human reproductive function. We postulate the existence of a prorenin receptor which activates prorenin and, in consequence, activates a local renin-angiotensin system. The functioning of this system may be regulated by changes in prorenin and its receptor.

Animals↗
PubMed1987

Follicular fluid estradiol and progesterone are markers of preovulatory oocyte quality.

Follicular fluid estradiol (FF E2) and progesterone (P) have previously been shown to vary with the maturation of the follicle. A profile of follicular fluid E2 and P was obtained from follicles of 19 preovulatory oocytes, which resulted in normal term pregnancies from single embryo transfers. A narrow band was defined around the linear regression line E2/P = 1.2 X 10(-2) + 1.57 X 10(-4) E2, r = 0.806, P less than 0.01, when E2/P was plotted versus E2 that included 84.2% of these oocytes. Eleven of the 19 pregnancies were clustered between an E2 of 240 to 460 ng/ml and an E2/P ratio of 0.044 to 0.084. Sixty-eight patients undergoing in vitro fertilization and embryo transfer were studied. A significantly greater number of preovulatory follicles from the fertilized, cleaved, and pregnant group (10 of 40) was found in the cluster than from the fertilized, cleaved, but not pregnant group (4 of 46; P = 0.04) and fertilized but not cleaved group (0 of 13; P = 0.04). Significantly more pregnant patients (14 of 20) had a preovulatory follicle within the band than nonpregnant patients (11 of 36) (P less than .02), as well as in the cluster (10 of 20), compared with 4 of 36, respectively (P less than 0.01). It may be concluded that a range of FF E2 and E2/P values define a stage of maturation that is compatible with successful pregnancies.

Estradiol↗
PubMed1986

Prorenin as a reproductive hormone. New form of the renin system.

Prorenin, the biosynthetic precursor of renin, is synthesized by the kidneys. Herein is reviewed recent evidence that the ovaries also secrete prorenin. It was found that prorenin is present in mature human ovarian follicular fluid in extremely high concentrations and that plasma prorenin levels increase transiently in blood during the menstrual cycle at the time of ovulation. No change in plasma active renin levels occurs at this time. Plasma prorenin level also increases 10-fold in pregnant women very soon after conception. The ovaries are apparently the source of this rise, since plasma prorenin levels did not increase in a pregnant woman with ovarian failure who received a donor egg. All of these changes in plasma prorenin levels appear to be caused by gonadotropic hormones. These results suggest a role for ovarian prorenin in human reproductive function. They may have relevance to studies of female infertility, birth control, and toxemia of pregnancy. They also suggest that a renin system exists that is regulated by changes in prorenin.

Animals↗
PubMed1986

Plasma prorenin during early pregnancy: ovarian secretion under gonadotropin control?

To explore the time-course and the source of the changes in plasma prorenin that occur in early pregnancy we studied a normal subject (subject 1), an in vitro fertilization (IVF) patient (subject 2) and an ovarian failure patient who received a donor egg (subject 3). Day 0 was the luteinizing hormone (LH) peak (subject 1), the day of human chorionic gonadotropin (hCG) administration (subject 2) or 3 days before embryo transfer (subject 3). In subjects 1 and 2 prorenin increased transiently (three- and ninefold respectively) on days 0-4, then returned towards baseline and began to increase again around day 12 to a maximum (six- and 26-fold baseline) around day 20. Active renin was consistently less than 10% of total renin. In the ovarian-failure patient only small fluctuations occurred in total renin yet her hCG was 137 mlU/ml on day 15, proving that she was pregnant. These results suggest that the prorenin rise that occurs at mid-menstrual cycle and following conception may be due to ovarian prorenin secretion in response to stimulation by gonadotropic hormones.

Adult↗
PubMed1985

Lactate uptake by the fetal sheep liver.

Lactate is produced by the sheep placenta and is an important metabolic substrate for fetal sheep. However, lactate uptake and release by the fetal liver have not been assessed directly. We measured lactate flux across the liver in 16 fetal sheep at 129 (120-138) days gestation that had catheters chronically maintained in the fetal descending aorta, inferior vena cava, right or left hepatic vein, and umbilical vein. Lactate and hemoglobin concentrations and oxygen saturation were measured in blood drawn from all vessels. Umbilical venous, portal venous, and hepatic blood flow were measured by injecting radionuclide-labeled microspheres into the umbilical vein while obtaining a reference sample from the descending aorta. We found net hepatic uptake of lactate (5.0 +/- 4.4 mg/min per 100 g liver). A large quantity of lactate was delivered to the liver (94.2 +/- 78.1 mg/min per 100 g), so that the hepatic extraction of lactate was only 7.7 +/- 6.5%. Hepatic oxygen consumption was 3.18 +/- 3.3 ml/min per 100 g, and the hepatic lactate/oxygen quotient was 2.07 +/- 1.54. There was no significant correlation between hepatic lactate uptake and hepatic lactate or glucose delivery, hepatic oxygen consumption, hepatic blood flow, hepatic glucose flux, total body oxygen consumption, arterial pH, oxygen content, or oxygen saturation. There was, however, a significant correlation between hepatic lactate uptake and umbilical lactate uptake (r = 0.74, P less than 0.005) such that net hepatic lactate uptake was nearly equivalent to that produced across the umbilical-placental circulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Effects of fetal-maternal exchange transfusion on fetal oxygenation and blood flow distribution.

The effect of reducing hemoglobin affinity for O2 on fetal oxygenation was assessed in seven fetal lambs in which fetal blood was almost completely replaced by maternal blood 2-3 days postoperatively. Measurements of fetal blood gases and organ blood flow (radionuclide-labeled microsphere technique) were obtained before and 1 h after the exchange transfusion. Umbilical venous blood PO2 increased from 29 +/- 5 to 35 +/- 6 (SD) Torr (P less than 0.001) but hemoglobin O2 saturation decreased from 78.2 +/- 10.3 to 39.8 +/- 8.8% (P less than 0.001), resulting in a 46% decrease in umbilical venous blood O2 content. Since umbilical-placental blood flow also decreased (P less than 0.002), O2 delivery to the fetus decreased by 64% (P less than 0.002). Although O2 extraction increased from 32.5 +/- 6.8 to 50.9 +/- 9.0% (P less than 0.002), fetal O2 consumption fell from 7.28 +/- 1.97 to 4.10 +/- 1.20 ml X min-1 X kg-1 (P less than 0.02), and metabolic acidemia developed. No significant change in fetal cardiac output was observed. Blood flow increased significantly to the myocardium and adrenals but fell in the placenta, carcass, and lungs and was maintained in other organs. This resulted in a significant decrease in the amount of O2 delivered to all fetal organs except to the myocardium in which it was maintained. In the sheep the higher affinity of fetal blood hemoglobin for O2 helps maintain normal oxygenation during fetal life by facilitating O2 uptake at the placenta and unloading O2 in the tissues.

Animals↗
PubMed1984

Fetal adaptations to spontaneous hypoxemia and responses to maternal oxygen breathing.

Circulatory adaptations to spontaneous hypoxemia were assessed with the microsphere method at 119-123 days gestation in ovine fetuses who were subsequently found to be growth retarded. Combined ventricular output tended to be increased and it was redistributed so that oxygen delivery to the heart was increased by over 50%, oxygen delivery to the lung and placenta were decreased, and that to other organs, including the brain, were maintained. Maternal oxygen breathing for 1 h not only reversed these adaptations, but also produced an augmented lung blood flow. Umbilical blood flow was not affected. These findings have clinical implications for the growth-retarded fetus about to undergo the stress of labor.

Animals↗
PubMed1983

Heart rate and blood pressure responses to umbilical cord compression in fetal lambs with special reference to the mechanism of variable deceleration.

We examined heart rate and blood pressure responses to umbilical cord compression in fetal lambs. Fetal heart rate (FHR) responses resembling variable deceleration occurred only after umbilical blood flow was reduced by at least 50%. These changes during partial cord occlusion varied directly with the reduced umbilical blood flow and were abolished by atropine; no significant changes in arterial pressure were observed. Complete cord occlusion caused severe bradycardia, a progressive increase in arterial pressure, and delayed recovery of FHR. With partial cord occlusion, the bradycardia was of chemoreceptor origin and was vagally mediated; with complete occlusion the bradycardia may have resulted from both chemoreceptor and baroreceptor stimulation. During prolonged partial cord occlusion, FHR decreased initially, then recovered to above control value; this occurred in the face of a significant acidosis. Thus, FHR responses to cord compression are dependent on the actual percentage of reduction in umbilical blood flow and on its duration.

Animals↗
PubMed1983

The effect of reducing umbilical blood flow on fetal oxygenation.

To assess the effect of various degrees of umbilical cord compression on fetal oxygenation, we instrumented fetal lambs at 120 to 128 days' gestation. An electromagnetic flow transducer was placed around the common umbilical artery to record umbilical blood flow flow continuously. Catheters were passed into an umbilical vein and a hind limb artery and vein, and a balloon occluder was placed around the umbilical cord. After recovery from operation, umbilical blood flow was reduced to 75%, 50%, and 25% of control values by controlled cord occlusion. Umbilical venous oxygen content did not change during cord compression; thus, oxygen delivery was linearly related to umbilical blood flow. Oxygen consumption of the fetus was maintained with reduction of umbilical blood flow to about 50% of control values; further reductions were associated with a progressive fall in fetal oxygen consumption. With reduced umbilical flow, there was a progressive increase in oxygen extraction from a control of 33.6% +/- 4.8% to 67.7% +/- 11.3% during 75% reduction of flow.

Animals↗
PubMed1983

Baroreflex control of the circulation in chronically instrumented fetal lambs.

The role of the arterial baroreceptors in regulating the fetal circulation was studied in 18 chronically instrumented fetal lambs, 120-136 days gestation. The results were compared to those obtained in three sinoaortic denervated adult sheep. Nine fetuses underwent sinoaortic denervation and nine fetuses served as sham-operated controls. Two to 3 days after surgery, heart rate and blood pressure were recorded continuously and analyzed over 1-hour periods. In the denervated fetuses, marked fluctuations of the arterial pressure and heart rate were observed. Frequency distribution curves for mean arterial pressure and heart rate showed broader and flatter curves in the denervated fetuses. The average mean arterial pressure and heart rate were not significantly different between the two groups. However, the standard deviation as an index of variability of the mean arterial pressure increased from 2.7 +/- 0.9 (mean +/- standard deviation) in the control group to 6.5 +/- 2.4 in the denervated fetuses, and the standard deviation of the heart rate increased from 10.6 +/- 2.1 to 21.5 +/- 5.7. In the adult sheep, mean arterial pressure and heart rate increased on the 1st day after denervation and returned to near control values on the 3rd day. The variability of the mean arterial pressure increased, but that of the heart rate did not change. Fetal cardiac output and its distribution were measured by the radionuclide-labeled microsphere technique. Combined ventricular output was not statistically different between the groups, but the blood flow to the fetal body was 27% higher in the denervated fetuses. The calculated fetal body vascular resistance was 31% lower in the denervated lambs. This study indicates that the arterial baroreceptors are important in regulating variability of the arterial pressure and heart rate in fetal life, and also may have a significant role in maintaining the normal peripheral vascular resistance.

Animals↗
PubMed1983

Hepatic oxygen and glucose metabolism in the fetal lamb. Response to hypoxia.

Although the fetal liver is an active metabolic organ, its oxygen and glucose requirements have not previously been described. We measured hepatic blood flows and the oxygen and glucose differences across the liver in 12 late gestation fetal lambs in utero. Four animals were studied at least 1 wk postsurgically and again 2-5 d later to assess daily variations in hepatic blood flow and metabolism (group I). A second group of eight animals was studied 3-5 d postsurgically during a control period and during acute fetal hypoxia (group II). Under control conditions total hepatic blood flow averaged 400 ml/min per 100 g in both groups, and 75-80% was of umbilical origin. Liver blood flow and oxygen consumption were usually similar during repeated measurements, but in one animal varied considerably. During periods of normoxia, oxygen consumption for both the right and left lobes of liver was 4 ml/min per 100 g. Oxygen consumption of the whole liver accounted for 20% of total fetal oxygen consumption. This was achieved with oxygen extraction of 10-15%, so that hepatic venous blood was well oxygenated and provided an important source of oxygen for other fetal tissues. Under control conditions we could demonstrate no net hepatic uptake or release of glucose suggesting that the liver ultimately utilizes another carbon source to support its oxidative metabolism. During acute hypoxia total liver blood flow and its umbilical venous contribution both fell by 20%. Blood flow to the right lobe of the liver fell twice as much as that to the left lobe. Hepatic oxygen consumption was linearly related to oxygen delivery during the control and hypoxic periods. Consequently, right hepatic oxygen uptake fell by 45% whereas left hepatic oxygen uptake was unchanged, suggesting a functional difference between the lobes. During hypoxia glucose was released from both liver lobes; 6 mg/min per 100 g for the right lobe and 9 mg/min per 100 g for the left lobe. Total hepatic release of glucose was estimated to nearly equal umbilical uptake, so that 45% of the glucose available to fetal tissues was of hepatic origin. We conclude that the fetal liver responds to acute hypoxia by reducing its own oxygen consumption and releasing glucose to facilitate anaerobic metabolism.

Animals↗
PubMed1983

Maturation of circulatory responses to methionine-enkephalin.

The cardiovascular and respiratory effects of the naturally occurring endogenous opiate, methionine-enkephalin, were studied in 23 fetal sheep, five newborn lambs, 15 pregnant sheep, and four nonpregnant ewes. The opiate peptide produced dose-dependent decreases in heart rate and blood pressure in fetal and neonatal lambs but increased heart rate and blood pressure followed immediately by decreased heart rate and blood pressure in pregnant ewes. The circulatory responses were examined by pharmacologic blockade of receptor activity and by vagotomy. The bradycardia and hypotension in the fetus and tachycardia and hypertension in the adult were shown to be mediated by autonomic efferent nerves. Sinoaortic denervation did not affect the fetal responses to infused enkephalin. Respiration decreased in fetal as well as postnatal animals even at doses of methionine-enkephalin that did not significantly affect heart rate and blood pressure. These data indicate that the cardiovascular effects of infused enkephalins undergo maturational changes and are mediated by the autonomic nervous system.

Aging↗
PubMed1982

Effects of naloxone on fetal circulatory responses to hypoxemia.

The effects of opiate receptor antagonism on the fetal cardiovascular response to hypoxemia were examined by means of the radionuclide-labeled microsphere technique. Heart rate, blood pressure, and cardiac output were measured during baseline periods, during hypoxemia, and before and after infusion of either naloxone (1 mg/kg) or an equivalent volume of 0.0% saline solution. Seventeen fetal sheep were subjected to maternal hypoxemia by allowing the ewes to breathe 10% oxygen (3% carbon dioxide, 87% nitrogen). The fetuses responded with bradycardia (p less than 0.002 compared with control), increased blood pressure (p less than 0.002 compared with control), and no significant change in combined ventricular output or placental blood flow. After naloxone, the bradycardia increased by 10% (p less than 0.001), and both combined ventricular output and placental blood flow fell by 20% (p less than 0.01 and p less than 0.01, respectively). The fetal bradycardic response to naloxone was reversible with atropine. In fetuses with normal oxygenation of the blood (normoxemic), naloxone had no significant effect on heart rate and blood pressure. These data indicate that endogenous opiates (e.g., endorphin and enkephalin) are important in regulating the fetal circulation during hypoxia, and that the effects of opiate receptor antagonism may be mediated through the autonomic nervous system.

Animals↗
PubMed1982

The mechanism of late deceleration of the heart rate and its relationship to oxygenation in normoxemic and chronically hypoxemic fetal lambs.

The responses of fetal heart rate and blood pressure to a transient reduction in uterine blood flow were studied in normoxemic and chronically hypoxemic lambs. In normoxemic fetuses, a reduction in uterine blood flow, if prolonged sufficiently, produced reflex bradycardia mediated through chemoreceptors and was associated with a decrease in carotid arterial PO2 to below 20 torr. The bradycardia was associated with a marked decrease in left ventricular output as measured by electromagnetic flowmeter; both were abolished by atropine. In chronically hypoxemic fetuses, a reduction in uterine blood flow produced a delayed deceleration of the heart rate which consisted of three components: reflex bradycardia due to chemoreceptor stimulation; baroreceptor-mediated reflex bradycardia which involved the slow and late recovery of the heart rate; and nonreflex bradycardia which was probably secondary to hypoxic myocardial depression. Quantitative analysis revealed a relationship between the components of delayed deceleration and the status of fetal oxygenation prior to the reduction in uterine blood flow. The lower the carotid arterial PO2, the shorter was the delay in the onset of bradycardia, the greater the decrease in heart rate, and the more prolonged the duration of bradycardia. The conclusion is that the response of fetal heart rate to a transient reduction in uterine blood flow is related to the duration of the reduction and to the status of fetal oxygenation prior to the decrease in uterine blood flow.

Animals↗
PubMed1982

Effects of hemorrhage on umbilical venous return and oxygen delivery in fetal lambs.

The effect of acute hemorrhage (21.7 +/- 1.6%, mean +/- SE of the estimated blood volume) on the distribution of the umbilical venous return (UVR) and oxygen delivery to fetal organs (radionuclide microsphere technique) was studied in 10 chronically catheterized fetal lambs. Hemorrhage decreased UVR and total oxygen delivery to the fetus by 23 and 28%, respectively (P less than 0.001). A greater proportion of the UVR bypassed the liver through the ductus venosus (DV) (P less than 0.01). Consequently, DV blood flow was relatively maintained, and liver blood flow and oxygen delivery derived from the UVR decreased by 41 and 45%, respectively (P less than 0.002). The proportion of cardiac output constituted by DV blood increased by 30% (P less than 0.01). The changes in the distribution of the DV blood were similar to the changes in the distribution of cardiac output. As a result the proportion of organ blood flow and oxygen delivery derived from DV blood increased by 30% in both the upper and lower body organs. These studies show that fetal hemorrhage has a marked effect on the distribution of the UVR to the liver. The preferential distribution of the DV blood to the heart and brain is maintained but not enhanced. Our results indicate that changes in distribution of the DV-derived blood and oxygen following fetal hemorrhage is determined primarily by the responses of the arterial circulation, i.e., circulatory afterload.

Animals↗
PubMed1982

Denervation of arterial chemoreceptors and baroreceptors in fetal lambs in utero.

Arterial baroreceptors and chemoreceptors were denervated in eight fetal lambs in utero. Carotid sinus and carotid body denervation was accomplished by stripping the carotid artery rostral and caudal to the origin of the occipital and lingual arteries. Aortic bodies were denervated by section of the superior laryngeal nerve and aortic nerve in the neck. The anatomy relevant to the technique is presented. The effectiveness of the denervation was tested by injection of 20 micrograms phenylephrine. The slowing of the fetal heart rate normally present in the intact lambs was abolished in the denervated fetuses. Denervation of the carotid and aortic chemoreceptors abolished the reflex bradycardia following injection of 200 micrograms cyanide or following acute hypoxemia produced by uterine blood flow reduction for 20 s. These results indicate that the baroreflex and chemoreflex can be elicited in utero and eliminated by the method we described. The preparation we present allows the study of the role of the arterial chemoreceptors and baroreceptors in normal fetal cardiovascular regulation and in fetal responses to stress.

Animals↗
PubMed1981

The acute effect of metoclopramide on plasma prolactin during pregnancy.

The effect of metoclopramide on plasma prolactin levels was studied in 10 women in the second half of pregnancy. The IV injection of 10 mg metoclopramide produces a significant rise in prolactin in 15 minutes, a peak of up to 6.5-fold over basal levels at 30 minutes and a sustained significant elevation for at least 4 hours. The results of this study indicate that maternal plasma protein levels although elevated, are still under inhibitory control and that the prolactin releasing capacity of the pituitary is maintained during pregnancy. The elevated hyperprolactinemia induced by metoclopramide may be of help in investigating the role of prolactin in human pregnancy.

Female↗