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Biomedical subjects

L L Peeters

Publications and source records attributed to L L Peeters.

At least 55 records · Page 3Linked to original sources

Salt-induced hypertension in Dahl salt-sensitive rats. Hemodynamics and renal responses.

This study was performed with Dahl salt-sensitive (DS) and Dahl salt-resistant (DR) rats to detect differences in cardiovascular hemodynamics and renal responses that might be involved in initiating salt-induced hypertension in DS rats. The effects of 4 weeks of 8% NaCl diet were studied in conscious, male DR and DS rats in which vascular and urinary catheters had been previously implanted. Results were compared with those obtained from control groups of DR and DS rats on 4 weeks of 1% NaCl diet. DR rats on 8% salt diet did not develop hypertension, and cardiac output and blood volume were unchanged; glomerular filtration rate, urinary flow, sodium excretion, and plasma atrial natriuretic factor (ANF) increased. DS rats on 8% salt diet developed hypertension, and cardiac output and blood volume increased; glomerular filtration rate, urinary flow, and sodium excretion did not change, despite an increase in ANF. DS and DR rats on 1% NaCl diet were subjected to ANF infusion. After ANF infusion DR rats had a decreased blood volume and an increased glomerular filtration rate, urinary flow, and sodium excretion; DS rats showed no significant changes in blood volume, glomerular filtration rate, urinary flow, or sodium excretion. ANF caused vasodilation in all regions studied in DR rats; DS rats showed vasodilation in all regions except the kidney. After acute volume expansion, although both DR and DS rats responded by an increase in cardiac output, only DS rats developed prolonged hypertension. This finding suggests an inadequate vasodilatory mechanism in DS rats. In response to acute volume expansion, renal resistance decreased in DR rats but not in DS rats. It is concluded that the primary hemodynamic disturbance in DS rats with salt-induced hypertension is an increase in cardiac output caused by blood volume expansion in the absence of any vasodilation. Comparison of the responses of DS and DR rats to high salt diets, ANF infusion, and acute volume expansion indicates that the salt-induced hypertension in DS rats is initiated by a diminished renal response to ANF.

Animals↗

Role of maternal glucose as a metabolic substrate for the guinea pig conceptus.

Our study in pregnant guinea pigs was designed to determine whether the modest fractional contribution of glucose to the late-pregnant uterine caloric uptake was due to inadequate uterine glucose supply or to diminished uterine glucose demand. To this end, uterine uptake of glucose, O2, and lactate was measured in 27 late-pregnant guinea pigs with a wide range of litter sizes. A group of 11 mid-pregnant guinea pigs served as a reference. The fractional uterine uptake of glucose in mid- and late-pregnancy was 90 and 45%, respectively, confirming the indirect data calculated from different studies. In late pregnancy, uteroplacental blood flow (microspheres, -40%) as well as arterial glucose concentration (-30%) had decreased relative to mid-gestation, giving rise to a 60% lower wt-specific uterine glucose supply and a 21% lower wt-specific uterine glucose uptake. Inasmuch as fetal and placental glycogen stores become rapidly depleted after the 50th day of pregnancy, the lower uterine glucose uptake in late pregnancy appears to reflect inadequate uterine glucose supply rather than diminished fetal glucose demands. In late pregnancy, uterine caloric demand per kg is about 60% more than in mid-gestation, most likely associated with accelerated fetal fat accretion. Inasmuch as the latter appears to be mostly fueled by nonglucose fat precursors, it could explain why the glucose fraction of the uterine caloric uptake in late pregnancy has decreased by 50% instead of 21% as compared to mid-gestation. The reduction in arterial glucose concentration in late pregnancy was independent of litter size suggesting this phenomenon is to be a maturational adaptation rather than a sign of inadequate maternal glucose production.

Animals↗

Early pregnancy wastage: relationship between chorionic vascularization and embryonic development.

The chorionic villous vascularization of 40 patients with first trimester spontaneous abortion was compared with that of 10 patients undergoing legal abortion (control group). The spontaneous abortion group was subdivided into a group with intrauterine embryonic death (n = 20) and a group with blighted ova (n = 20). Villous vascularization appeared unaffected after prolonged postmortem intrauterine retention. The incidence of vascularized villi was 89% in the control group, 26% in the group with embryonic death, and 9% in the group with blighted ova. In addition, the vascular density of vascularized villi was three to four times higher in the control group than in the two spontaneous abortion groups. The present study provides evidence that, in case of embryonic death and blighted ova, chorionic villous vascularization is deficient.

Abortion, Spontaneous↗

Transient diabetes insipidus of pregnancy.

The history is presented of a near-term patient with transient diabetes insipidus. Because of the demonstrated positive response to dDAVP it is argued that increased vasopressinase activity may have been involved.

Adult↗

Relationship between maternal hemodynamics and hematocrit and hemodynamic effects of isovolemic hemodilution and hemoconcentration in the awake late-pregnant guinea pig.

The relationship between the spontaneous hematocrit (Hct) and maternal hemodynamics and the hemodynamic effects of experimentally induced changes in this Hct were studied in the awake late-pregnant guinea pig. In animals with a relatively low Hct, cardiac output fractions and blood flows to brain and heart determined with microspheres were higher and those to kidneys lower than in animals with a relatively high Hct. The O2 flows to the kidneys and skin in the former animals were also lower. Cardiac output, heart rate, systemic blood pressure, and blood flows to the other organs, including the placenta, were not related to the Hct. Placental blood flow was found to vary in proportion to cardiac output. Both hemodilution and hemoconcentration induced changes in the cardiac output distribution and organ flows which resembled those observed in the spontaneous relation with Hct. In addition, hemodilution decreased systemic blood pressure. Both hemodilution and hemoconcentration increased placental blood flow; the magnitude of this flow increase was twice as high after hemodilution. The changes in oxygen flows after experimentally induced hemodilution and hemoconcentration appears to be directly related to the concomitant change in whole blood oxygen capacity. It is concluded that in the awake late-pregnant guinea pig, only brain, heart, and kidney perfusion vary in relation to the arterial Hct. The higher placental blood flow after isovolemic hemodilution may be a result of better blood rheology in the porous-like intervillous space of the placentas in a state of reduced systemic blood pressure. The modest rise in placental blood flow after isovolemic hemoconcentration appears to be mostly related to the methodology employed.

Animals↗

Placental transfer of Org 10172, a low-molecular weight heparinoid, in the awake late-pregnant guinea pig.

The placental transfer of Org 10172, a low-molecular weight heparinoid, was determined in 12 awake late-pregnant guinea pigs. Nine animals receiving placebo served as controls. After 5 days i.v. treatment with Org 10172 (2 x 300 anti-Xa U/kg/day), anti-Xa activity in fetal plasma amounted to 2.4% of the maternal concentration. The Org 10172 transfer across the placenta was also evaluated with 3H-labelled Org 10172. One hour after the administration of the latter compound, fetal Org 10172-bound 3H-activity had reached 1.5% of the maternal value. The associated extremely low placental Org 10172 transfer indicates that the Org 10172 transport across the placenta of the guinea pig is membrane-limited and that the placental permeability is negligibly low. Since the hemochorial placenta of the guinea pig closely resembles that of the human, it is likely that similar transplacental transfer properties of Org 10172 apply to man.

Animals↗

Movement of oxygen, glucose, and lactate across the uterus of the awake near-term guinea pig.

In this study the uterine movement of oxygen, glucose, and lactate was quantitated in the awake late pregnant guinea pig. Mean uterine uptake of oxygen per kg of uterus with conceptus was 581 mumol min-1, which is comparable to the value reported for the awake near-term rabbit, but 30% higher than the value reported for the awake near-term sheep. Experiment-related anemia in some animals was associated with a reduced uterine oxygen uptake. The arteriovenous oxygen difference across the uterus correlated positively with the arterial oxygen content and the hemoglobin concentration and negatively with uteroplacental blood flow. Uterine oxygen uptake showed a positive correlation with both the arterial hemoglobin and the uteroplacental blood flow. Uterine lactate output accounted for 20% of uterine glucose uptake, assuming maternally derived glucose to be the only source for uterine lactate output. After correction for this lactate output, the uterine glucose uptake was 96.5 mumol min-1 X kg-1 of pregnant uterus. This value is 30% higher than in the awake near-term rabbit and more than twice as high as that in the awake near-term sheep. Nevertheless, because of the high uterine demand for substrates, this uterine glucose uptake could only cover 45% of the caloric requirements of the pregnant uterus. The late pregnant guinea pig fetus may derive as much as 55% of its caloric uptake for fat deposition and protein accretion. Therefore, it is likely that the nonglucose uterine caloric uptake in the late pregnant guinea pig consists predominantly of fat precursors and amino acids.

Anemia↗

Uterine arterial and venous concentrations of glucose, lactate, ketones, free fatty acids, and oxygen in the awake pregnant guinea pig.

The concentration differences across the pregnant uterus of glucose, lactate, ketoacids, free fatty acids (FFA), and oxygen were determined in 21 chronically catheterized guinea pigs. Polyvinyl catheters were inserted into one of the ovarian veins and the right carotid artery around the 50th day of pregnancy. Postoperative recovery of maternal substrate concentrations in this preparation was evaluated in five animals. Elevated hemoglobin and ketoacid concentrations persisted up to the 4th day after surgery in the awake animal. In 16 animals between 54 and 62 days gestation, arterial and venous blood samples were collected between the 4th and 13th postoperative days. Arteriovenous substrate differences across the pregnant uterus (means +/- SD) were as follows: glucose, 0.87 +/- 0.22 mM; lactate, 0.31 +/- 0.11 mM; and oxygen 4.77 +/- 0.58 mM. There was no significant difference for ketoacids. In 10 animals, plasma FFA concentrations were determined. In nine animals, the arterial concentration was higher suggesting a net uptake of FFA by the pregnant uterus. Lactate production by the uterus accounted for approximately 18% of uterine glucose uptake if glucose is assumed to be the only source of uterine lactate production. The mean glucose/oxygen quotient across the uterus corrected for lactate output was 0.92 +/- 0.34. It is concluded that glucose is a major metabolic substrate for the near-term uterus in the pregnant guinea pig and can account for most of the uterine oxygen consumption.

Animals↗

Blood sampling from the ovarian vein in the unstressed pregnant guinea pig.

A new technique is described which allows sampling of blood from the ovarian vein in the pregnant guinea pig, after recovery from surgery and anesthesia. The technique involves retrograde insertion of a double catheter into the thoracic inferior vena cava from the right jugular vein. The outer catheter serves as a guide for the inner catheter which is advanced into either ovarian vein. The overall rate of success was 45% in 40 animals near term. Sampling of blood from the ovarian vein in the conscious animal remained possible for up to 17 days after surgery. Since in the pregnant guinea pig the ovarian veins drain most of the uteroplacental blood, the technique of retrograde cannulation of the ovarian vein allows study of uteroplacental metabolism in the conscious pregnant animal during prolonged periods.

Animals↗

Uteroplacental blood flow during pregnancy in chronically catheterized guinea pigs.

Uterine blood flow and its distribution to uterus, placenta and subplacental structures was measured in 18 pregnant guinea pigs studied under chronic steady-state conditions. Maternal cardiac output averaged 266 +/- 14 ml/min. Placental blood flow (PBF) remained less than 4 ml/min until 50 days gestation, after which it increased rapidly, attaining flows of 16 ml/min at term. PBF also increased linearly with placental weight (r = 0.76, P less than 0.001); however, the increase in PBF with gestational age is evident even in narrow weight ranges, indicating hyperperfusion of term placentas relative to those earlier in gestation. Fetal weight correlated with measured placental blood flow supplying the corresponding placenta after 50 days gestation (r = 0.72, P less than 0.001).

Animals↗

Distribution of cardiac output in the unstressed pregnant guinea pig.

Cardiac output (CO) and organ flows were measured in five nonpregnant and 14 pregnant unstressed guinea pigs between the thirty-ninth and sixty-fifth postconceptional day by means of radionuclide-labeled microspheres. Blood pressure, heart rate, and cardiac output in nonpregnant animals were 60 torr, 234 bpm, and 248 ml/min, respectively. These parameters did not change significantly during pregnancy. The uterine fraction of cardiac output increased to approximately 18% at term and there was an equivalent decrease in the CO fractions to the carcass and skin. Blood flow per gram of wet weight increased during pregnancy by approximately 140% and 70% for the thyroid and gastrointestinal tract, respectively, but did not change significantly for the heart, brain, kidneys, and adrenals. In pregnant animals near term the weight of the heart, kidneys, intestines, and lungs was approximately 25% lower than that observed in nonpregnant guinea pigs.

Animals↗

Retinal and choroidal blood flow in unstressed fetal and neonatal lambs.

The relationship between retinal blood flow (RBF) and choroidal blood flow (ChBF) and the oxygen content of arterial blood was investigated in 12 fetal lambs. The postnatal changes in these flows were studied in twelve newborn lambs. RBF and ChBF were determined by means of radioactive microspheres 3 to 10 days after implantation of the injection and sampling catheters. Fetal blood flows were measured at different levels of oxygenation. The postnatal flows were measured while the lamb breathed room air. The fetal data suggest an inverse relationship between RBF and arterial oxygen content. Concomitant changes in fetal ChBF were unrelated to arterial oxygen content. Because of the inverse relationship between RBF and arterial oxygen content, the product of RBF and arterial oxygen content was independent of the state of fetal oxygenation. RBF did not change with birth, whereas ChBF increased. There was no change in RBF with postnatal age whereas ChBF decreased significantly with increasing age.

Animals↗

Redistribution of cardiac output and oxygen delivery in the hypoxemic fetal lamb.

In hypoxia, fetal cardiac output and the product arterial O2 content x blood flow to the fetal heart and central nervous system (CNS) tend to remain constant. As a consequence the percentage of cardiac output directed to the heart and CNS increases hyperbolically in inverse relation to the oxygen content of the fetal ascending aorta, [O2]as. The fetal lamb maintains [O2]as approximately 0.45 mM (0.45 +/- 0.02 SEM) higher than the O2 content in the abdominal aorta, [O2]ab, over a wide range of oxygenation. When [O2]as decreases below the 2 mM level, the [O2]as--[O2]ab difference (delta O2) decreases also. A mathematical model of the fetal circulation shows that delta O2 is a function of the ratio oxygen consumption of fetal upper body/abdominal aorta blood flow (VU/FA). The behavior of delta O2 in hypoxia can be explained by assuming that the VU/FA ratio is maintained in moderate hypoxia and decreases in sever hypoxia.

Animals↗

Blood flow to fetal organs as a function of arterial oxygen content.

In a sheep preparation the blood flow to fetal organs was studied 3 to 10 days after surgery by means of the microsphere technique over a range of fetal arterial O2 content from 6 to 1 mM. Blood flows to neural tissues (cerebrum, cerebellum, brain stem), heart, and the adrenals increased in inverse relation to arterial O2 content. As a result the arterial supply of O2 to these organs tended to remain constant over the O2 range studied. Blood flow to the fetal lungs decreased progressively with hypoxia. The blood flow to kidneys, digestive tract, pancreas, and carcass had a tendency to remain constant or increase gradually in the transition from high to moderately low levels of arterial O2 content and then to decrease abruptly in more severe hypoxia. Umbilical blood flow did not change systematically in relation to arterial O2 content.

Acid-Base Equilibrium↗

Regulation of cerebral blood flow in the ovine fetus.

The effects on fetal cerebral blood flow (Qc) of changes in the carotid arterial and sagittal sinus venous PO2, PCO2, and oxygen content were studied in the chronically catheterized ovine fetus in utero at 130-140 days of gestation. Forty-seven measurements of Qc were made in 20 fetuses with radioactive microspheres. In 11 of these animals, 84 measurements of cerebral arteriovenous differences of oxygen content were performed, permitting an indirect measurement of cerebral blood flow (Qc*), assuming a constant cerebral metabolic rate. Arterial and, in 11 animals, sagittal sinus blood was withdrawn for analysis of PO2, PCO2, oxygen content, and pH at the time of the flow measurements. Preliminary analysis showed the best predictor of Qc and Qc* to be the reciprocal of the arterial oxygen content (1/CaO2). Multiple linear regression analysis combining the effects of 1/CaO2 with arterial PCO2 (PaCO2) gave the following equations: Qc = 458.8 (1/CaO2) + 2.68 PaCO2 - 107.93 (R2 = 0.68); Qc* = 435.54 (1CaO2) + 2.20 PaCO2 - 75.03 (R2 = 0.86). As a result of the hyperbolic relationship between Qc (and Qc*) and CaO2, changes in CaO2 at the low levels found during intrauterine life exert an important influence on the fetal cerebral circulation.

Animals↗

Fetal cerebral oxygen consumption at different levels of oxygenation.

Cerebral oxygen consumption (VCO2) was measured in 10 unanesthetized, chronically catheterized fetal sheep at 130-140 days of gestation. The VCO2 was calculated using cerebral blood flow (QC) measured with radioactive microspheres and the cerebral arteriovenous difference of O2 content (C(a-V)O2) calculated from preductal arterial and sagittal sinus venous blood. The ewe was exposed to varying concentrations of oxygen, resulting in fetal arterial oxygen contents (CaO2) of 0.89-5.58 mM, arterial oxygen tension (PaO2) values of 14-36 Torr, and cerebral venous oxygen tension (PVO2) values of 9-25 Torr. Although there was a clear relationship between the fetal CaO2 and C(a-V)O2, this was shown to be the result of changes in Qc rather than changes in VCO2. There was not a statistically significant correlation between either CaO2 or PVO2 and VCO2 over this range of oxygenation. On the other hand, C(a-V)O2 was highly correlated with Qc. There is no evidence that VCO2 is a function of oxygen tension (PO2) in the unanesthetized fetal sheep as long as the sagittal sinus PO2 is greater than or equal to 9 Torr.

Animals↗

Serum levels of human placental lactogen and human chorionic gonadotropin in early pregnancy: a maturational index of the placenta.

Between weeks 10 and 20 of gestation, there are rapid and opposing changes in blood levels of two hormones produced by the syncytiotrophoblast; hPL increases and hCG decreases. In this study, the relationship between these two changing hormone levels was examined, rather than the serum concentrations themselves, as a potential test for placental maturation. The relationship between the hCG and hPL concentrations and GA determined in a selected group of patients was described by the following equation: GA (in days)=97.3 + 24.8 ln [hPL]-14.5 LN [HCG]. The endocrine evaluation of placental maturation by comparison of [hCG] and [hPL] in early pregnancy shows promise as a simple, safe, and inexpensive clinical tool for GA assessment.

Chorionic Gonadotropin↗

Volume-dependent echocardiographic parameters are not useful for estimating baseline blood volume but are useful for detecting acute changes in vascular filling state.

To assess the hypothesis that echocardiographic variables vary as a function of baseline blood volume and change in response to changes in vascular filling state, we evaluated the relationship between the atrial and ventricular dimensions and left ventricular function, as measured by combined Doppler and M-mode echocardiography on the one hand, and blood volume as measured by a standard radioactive isotope technique on the other. Furthermore, we determined the effect of an increment in vascular filling state induced by plasma volume expansion. Test subjects were ten male and six female volunteers. Blood volume/kg was the only factor not different between male and female subjects and therefore suitable for our study. None of the echocardiographic variables correlated with blood volume/kg. Volume loading increased stroke volume, left atrial diameter, right atrial area, left ventricular end-diastolic dimension, mean velocity of circumferential fiber shortening and left ventricular ejection time. It is concluded that echocardiographic variables are unsuitable for estimating blood volume. Serial measurements of atrial dimensions and left ventricular dimensions are useful for detecting rapid changes in vascular filling state.

Adult↗