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ABSTRACT: The fetal heart is highly sensitive to changes in mechanical load. We have previously demonstrated that increased cardiac load can stimulate cell cycle activity and maturation of immature cardiomyocytes, but the effects of reduced load are not known. Sixteen fetal sheep were given either continuous intravenous infusion of lactated Ringer solution (LR) or enalaprilat, an angiotensin-converting enzyme inhibitor beginning at 127 days gestational age. After 8 days, fetal arterial pressure in the enalaprilat-infused fetuses (23.8 +/- 2.8 mmHg) was lower than that of control fetuses (47.5 +/- 4.7 mmHg) (P < 0.0001). Although the body weights of the two groups of fetuses were similar, the heart weight-to-body weight ratios of the enalaprilat-infused fetuses were less than those of the LR-infused fetuses (5.6 +/- 0.5 g/kg vs. 7.0 +/- 0.6 g/kg, P < 0.0001). Dimensions of ventricular myocytes were not different between control and enalaprilat-infused fetuses. However, there was a significant decrease in cell cycle activity in both the right ventricle (P < 0.005) and the left ventricle (P < 0.002) of the enalaprilat-infused fetuses. Thus, we conclude a sustained reduction in systolic pressure load decreases hyperplastic growth in the fetal heart.
AJP Regulatory Integrative and Comparative Physiology 08/2010; 299(2):R573-8. · 3.34 Impact Factor
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Placenta 01/2009; 30(2):201-2. · 3.69 Impact Factor
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ABSTRACT: Two anaesthetic protocols were compared using pregnant sheep. In both groups of animals, anaesthesia was induced using an intravenous (i.v.) injection of diazepam and ketamine. The ewes were then intubated for positive pressure ventilation using 0.8 L/min of nitrous oxide and 2 L/min oxygen with 1.1-1.8% halothane. If the ewe showed any signs of awakening, one of two protocols was followed. First, the halothane concentration was increased to 2-3% until the ewe was completely anaesthetized. Second, the halothane concentration was not altered, but the ewe was given doses of i.v. diazepam (0.1 mg/kg) and ketamine (1 mg/kg) until again completely anaesthetized. At the completion of surgery, maternal recovery was rapid and similar between the two groups. However, five days after surgery, the fetal arterial Po(2) and oxygen content of the fetuses receiving additional halothane (1.9 +/- 0.2 kPa and 4.4 +/- 1.0 mL/100 mL) were statistically significantly depressed when compared with the fetuses receiving additional diazepam and ketamine (2.9 +/- 0.1 kPa and 7.0 +/- 0.5 mL/100 mL). These results led us to conclude that certain anaesthetic protocols, in spite of good maternal recovery, can lead to deleterious effects upon the fetus that persist for at least five days after surgery.
Laboratory Animals 08/2008; 42(3):326-30. · 1.21 Impact Factor
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ABSTRACT: Earlier studies suggested that the fetal placental circulation is relatively inert with fetal placental flow increasing or decreasing with perfusion pressure. Subsequent studies have demonstrated that the placenta may not be an unreactive vascular bed. The present study was undertaken to determine if plasma infusion-induced hypertension increased fetal placental flow in proportion to the driving pressure across the fetal placental circulation. Six fetal sheep were operated on at 118-122 days to place intravascular catheters and a flow sensor on the common umbilical artery. Starting 6 days later, the fetuses were infused with adult sheep plasma. During the 7-day-long infusion period, they received a total of 1515+/-217 (SD) ml of fluid and 93.2+/-12.0 g of protein. Fetal plasma protein concentrations increased from 34.2+/-2.3 to 77.0+/-9.7 g/l (P<0.0001). Fetal arterial blood pressures rose from 42+/-3 to 59+/-4 mmHg (P<0.01) and venous pressures rose from 2.2+/-0.5 to 4.8+/-0.8 mmHg (P<0.01). In spite of the large increase in driving pressure, fetal placental blood flow remained (statistically) constant (627+/-299 ml/min and 552+/-221 ml/min) while fetal umbilical resistance increased from 0.077+/-0.038 to 0.115+/-0.053 mmHg min/ml (P<0.01). On day 7, plasma renin activity had fallen from 6.7+/-4.2 ng/(ml/h) at preinfusion control to 0.6+/-0.6 ng/(ml/h) (P<0.05) and plasma angiotensin-II concentration had fallen from 33.2+/-26.6 to 6.2+/-3.9 pg/ml, although this fall was not statistically significant (P=0.07). Fetal placental flow did not increase with increased driving pressure across the fetal placental circulation. The increase in fetal placental resistance may be a response to the increase in arterial pressure since there was no increase in flow.
Placenta 08/2006; 27(8):876-81. · 3.69 Impact Factor
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ABSTRACT: Six fetal sheep were operated on at 118 to 121 days of gestation. The pulmonary end of the trachea was connected to the gastric end of the esophagus with a section of tubing. This left urine as the only source of amniotic fluid and intramembranous absorption as sole exit. Multiple indwelling fetal vascular, intra-amniotic, allantoic, and a fetal bladder catheter were placed. Beginning 5 days after surgery, all urine was drained from the bladder and immediately reinfused into the amniotic sac to monitor urine production rate. After 4 days of urine infusion alone, the urine infusion was augmented for 6 days with an intra-amniotic infusion of Ringer solution. Amniotic and allantoic fluid volumes were measured at autopsy. During the period of Ringer infusion, intramembranous absorption of amniotic fluid increased by more than 1,191 +/- 186 (SE) ml/day (P < 0.002) and the rates of Na(+) and Cl(-) absorption increased to more than five times (P < 0.005) and eight times (P < 0.005) their initial values. Only one of six fetuses had polyhydramnios. It is concluded that intramembranous absorption of amniotic fluid makes a strong regulatory adjustment in response to an abnormal increase in inflow of exogenous fluid.
The American journal of physiology 07/1999; 277(1 Pt 2):R236-42.
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J J Faber
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ABSTRACT: Transplacental clearances of Cl-, Na+, SO4(2-), mannitol, raffinose and inulin were measured in anaesthetized rats of 14-19 days gestational age. Water flow across the placenta was calculated from embryonic (74 per cent/day) and extra-embryonic fluid (94 mg/day) growth. Before 16 days, more than half of the tracer contents of the conceptuses were located in the extra-embryonic fluids. Clearances were not demonstrably affected by the presence or polarity of an electrical charge on the tracer. Clearances fell off with increasing molecular weights but faster than the corresponding decreases in the coefficients of free diffusion. The dimensions of the paracellular transplacental passages were calculated with the Patlak equation and equivalent pore theory. Pore radii were not significantly different from 3.3 nm at any gestational age but in the last 2 days, the geometric constant (number of pores per gram x pore area/pore length) increased threefold, to 31 cm/gram placental weight. The calculated parameters were insensitive to deletion of Na+ and Cl- from the data set. In haemochorial placentae, steric restriction does not prevent the entry into the embryo of solutes circulating in maternal blood, except for macromolecules.
Placenta 06/1999; 20(4):331-7. · 3.69 Impact Factor
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Placenta 12/1998; 19(8):675-6. · 3.69 Impact Factor
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ABSTRACT: Fetal cardiovascular control is effected by an interaction of the fetal somatic and placental circulations. Three primary regulatory mechanisms are involved: transplacental transfer of extracellular fluid, driven by a difference in hydrostatic and oncotic pressures; modulation of fetal placental and somatic vascular resistances by means of blood pressure controlled production of angiotensin; and somatic autoregulation of flow. A systems analysis incorporates these and other fetal cardiovascular functions and this analysis was modelled for computer simulation. Given physiologically plausible values for known cardiovascular parameters in the fetal sheep, the model reproduced in detail a variety of experimental protocols with known outcomes; these included the normal fetus, the fetus after bilateral nephrectomy, the nephrectomized fetus infused with angiotensin, the intact fetus infused with NaCl solutions, the fetus with lymphatic obstruction and the severely anaemic fetus. The systems analysis demonstrated that fetal cardiac failure constituted the strongest stimulus for the formation of fetal oedema of any tested pathological intervention.
Placenta 06/1997; 18(4):313-26. · 3.69 Impact Factor
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J J Faber
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ABSTRACT: Circulatory homeostasis is a difficult notion. The graphic format presented here facilitates the teaching of long-term control of systemic arterial blood pressure and cardiac output. It is based on the view that the following four "function curves" cooperate in long-term regulation: the relation between blood volume and ventricular filling pressure, the relation between ventricular filling pressure and cardiac output, the relation between cardiac output and peripheral resistance, and the relation between arterial pressure and natriuresis. Positioning the function curves in the format presented here clarifies their cooperativity. The distinction between a nonsteady state and a steady state deserves emphasis. Long-term pathophysiology of the circulation is most easily taught on the basis of the assumption that, generally, there will be a steady state. The format clarifies why some known physiological relations are almost impossible to demonstrate in the intact organism, and it discourages explanations of pathophysiology that are not firmly based on physiology.
The American journal of physiology 07/1996; 270(6 Pt 3):S40-9.
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ABSTRACT: It is known that a week-long infusion of angiotensin into fetal sheep produces polyhydramnios. The purpose of the present experiments was to determine whether an increased osmotic force across the placental barrier could account for the excess transfer of water. Six fetuses with indwelling catheters were infused with angiotensin-I and one with angiotensin-II; all, except one fetus in the first group, developed gross polyhydramnios. None of the transplacental concentration differences of the small plasma solutes Na+, Cl-, HCO3-, K+, urea, or glucose showed a demonstrable change and the same was true of the transplacental difference in freezing point osmolality and for the transplacental difference in plasma protein concentration. It is concluded that the infusion of angiotensin at a low dose rate is a reliable protocol for producing polyhydramnios. However, the present findings lend no support to the hypothesis that a primary change in transplacental osmotic force is the cause of the increased transplacental water transfer in this form of polyhydramnios. Alternative hypotheses are discussed in the light of recent discoveries.
European Journal of Obstetrics & Gynecology and Reproductive Biology 01/1996; 63(2):175-9. · 1.97 Impact Factor
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J J Faber
International Journal of Obstetric Anesthesia 11/1995; 4(4):230-7. · 1.39 Impact Factor
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ABSTRACT: 1. Maternal blood was made transiently hypertonic by rapid I.V. infusion of a concentrated mannitol solution into pregnant ewes bearing lambs with an indwelling flow sensor and vascular catheters. 2. The transplacental flows of water and of Na+ and Cl- were calculated from the umbilical arteriovenous differences in the concentrations of 125I-labelled albumin and electrolytes, and the fetal placental blood flow. 3. The reflection coefficients of Na+ and Cl- were calculated by means of the Patlak equation and found to be 0.85 +/- 0.04 and 0.68 +/- 0.04 (means +/- S.E.M.). The filtration coefficient was 1.02 x 10(-7) +/- 0.12 x 10(-7) cm5 dyne-1 s-1. 4. The results fitted best to an equivalent pore radius in the placental barrier smaller than the currently accepted 0.44 nm but not less than 0.35 nm.
The Journal of Physiology 09/1995; 487 ( Pt 1):159-67. · 4.72 Impact Factor
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J J Faber
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ABSTRACT: Transplacental clearances were measured for radiolabelled Cl-, SO4(2-), mannitol, sucrose, raffinose, PEG-900 and inulin. Maternal placental blood flows were measured with radiolabelled microspheres. At 18 days of gestation (term 31 days), the fetuses and extra-fetal fluids were growing at 55 and 32 per cent per day, accounting for a net transplacental filtration rate of 14.2 nl/sec per gram placental weight. Pore theory and a least squares fit of the Patlak equation yielded an equivalent pore radius of 1.75 nm. It was demonstrated that the clearance of the largest tracer, inulin, was 30 times higher than it would have been in the absence of net filtration. Comparison with literature data showed that there was a small increase in placental permeability per gram placenta between 14 and 18 days of gestation but that the increase between 18 and 28 days of gestation was about 14-fold for Cl- and 300-fold for inulin. There was no evidence for a decreasing equivalent pore radius in the course of gestation from 14-18 days.
Placenta 08/1995; 16(5):403-12. · 3.69 Impact Factor
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ABSTRACT: In pregnancy, the maternal circulating renin-angiotensin system (RAS) and uteroplacental tissue RAS has been thought to support maternal placental flow by raising maternal arterial pressure or changing placental vascular resistance. Also, the placenta or uterus may alter maternal circulating RAS. Recent studies in the authors' laboratory using chronically catheterized rabbits are compared with previous studies on interactions between the RAS and uteroplacental flow. When uterine driving pressure was reduced either mechanically or after converting enzyme inhibition, maternal placental flow decreased in proportion to change in driving pressure; myoendometrial flow did not change. Angiotensin II (AII) infusion to increase pressure by 21 +/- 2 mm Hg decreased placental but not myoendometrial flow. Thus, there is no evidence that maternal placental flow is autoregulated or supported by a specific renin-angiotensin mechanism. Normally, there is no net uterine release or uptake of active plasma renin activity, AI, or AII, but there is a small net release of trypsin-activated plasma renin activity (tPRA), presumably prorenin. Distal aortic occluder inflation produced upper-body hypertension, and uterine release of tPRA increased. There was a significant uterine arteriovenous concentration difference for AII during AII infusion. These methods are adaptable for studying interactions between uteroplacental flow and other vasoactive agents.
Reproduction Fertility and Development 02/1995; 7(6):1437-42. · 2.11 Impact Factor
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ABSTRACT: Nine bilaterally nephrectomized fetal sheep were infused for 6 days with angiotensin I in sterile water, and five nephrectomized fetal sheep were infused for 6 days with water alone. Total dose of angiotensin was 13.8 +/- 8.6 (SD) mg/kg fetal dry wt, and the total volumes of infused water were 303 +/- 201 and 423 +/- 164 ml, respectively. Of the fetuses infused with angiotensin I, one was of normal appearance, two showed moderate hydrops fetalis, and the remaining fetuses were grossly hydropic. All water-infused fetuses were normal. Their wet-to-dry weight ratios were 7.98 and 6.36 (P < 0.015), representing a 25% of normal body weight excess of water in the angiotensin I-infused fetuses. Six days of angiotensin I infusion caused a gradual rise in fetal arterial blood pressure from 37 +/- 15 to 81 +/- 15 mmHg (P < 0.05) and a gradual rise in venous blood pressure from 2.7 +/- 1.0 to 10.5 +/- 1.7 mmHg (P < 0.05). It was concluded that the fetal edema was due to the elevation in venous pressure. Plasma concentrations of Na+, K+, Cl-, HCO3-, total alpha-amino acids, fructose, glucose, and lactate in the fetus and the ewe did not identify an osmotically active solute responsible for the transplacental attraction of excess water into the conceptus, and the mechanism that attracted this excess water across the placenta remains unclear.
The American journal of physiology 01/1995; 267(6 Pt 2):R1522-7.
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ABSTRACT: The relationship between uterine driving pressure and maternal placental blood flow was studied after inflation of an aortic occluder previously placed between the renal and ovarian arteries in 10 conscious pregnant rabbits at 28 +/- 1 (mean +/- SEM) d of a 30- to 31-d gestation to test the hypothesis that there is autoregulation of maternal placental blood flow. After control measurements, the femoral artery pressure was reduced 22 +/- 3% from 83 +/- 5 mm Hg and clamped at 65 +/- 4 mm Hg (p < 0.001) for 54 +/- 4 min by servo control. Carotid artery pressure increased from 86 +/- 5 to 98 +/- 6 mm Hg (p < 0.01). There was no change in cardiac output (839 +/- 78 vs 814 +/- 64 mL/min; NS), upper-body flow (651 +/- 62 vs 671 +/- 55 mL/min; NS), or renal flow (111 +/- 14 vs 104 +/- 8 mL/min; NS). Blood flow to tissues below the occluder decreased from 188 +/- 18 to 143 +/- 14 mL/min for the lower body (p < 0.05), 153 +/- 15 to 116 +/- 11 mL/min for the hindquarters (p < 0.05), and 17.7 +/- 1.9 to 12.9 +/- 1.4 mL/min for 13 pregnant uterine horns (p < 0.05). Placental flow to live fetuses per horn decreased from 13.0 +/- 1.9 to 8.9 +/- 1.2 mL/min (p < 0.01), whereas there was no significant change in myoendometrial flow (4.0 +/- 0.3 vs 3.5 +/- 0.5 mL/min; NS). Uterine oxygen consumption was unchanged (1.15 +/- 0.16 vs 1.06 +/- 0.13 mL/min; NS).(ABSTRACT TRUNCATED AT 250 WORDS)
Pediatric Research 07/1994; 36(1 Pt 1):102-10. · 2.70 Impact Factor
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ABSTRACT: The role of the kidneys in the maintenance of arterial blood pressure was examined in fetal sheep. Surgery was performed on 11 pregnant sheep (8 twin pregnancies) at approximately 125 days. All 19 fetuses were instrumented with hindlimb arterial and venous catheters. Eleven of the fetuses (but only 1 of each twin) were also bilaterally nephrectomized. Fetal arterial blood pressure was measured several times between 2 and 14 days after surgery. Arterial blood pressure in the intact fetuses increased from 44 +/- 1 to 47 +/- 1 mmHg (SE) but gradually decreased from 37 +/- 4 to 25 +/- 3 mmHg in the nephrectomized group. Whereas the arterial blood pressures measured on the first day of the experiment were not statistically significantly different between the two groups, by the final day of the experiment the arterial blood pressure of the intact fetuses was much higher than that of the nephrectomized fetuses. Venous blood pressure was similar in the two groups. We conclude that bilateral nephrectomy in fetal sheep not only stops the normal gestational increase in arterial blood pressure but also leads to a progressive decline.
The American journal of physiology 02/1994; 266(1 Pt 2):H17-20.
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J J Faber
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ABSTRACT: The clearances of a series of hydrophilic probes (radii of 2-10 A) were determined in rabbit placentas of 13-15 days of gestation (term, 31 days). Maternal placental blood flows were measured by means of radiolabeled microspheres. None of the transfers of the tracers were limited by maternal or embryonic arteriovenous differences in the placenta, and the clearances decreased with increasing molecular radius. The transplacental water filtration rate calculated from conceptual growth was comparable in magnitude to the clearances of the largest tracers. Application of Patlak's modification of the Hertzian equation and pore theory suggested an equivalent pore radius of 17 A. Placental permeability surface area products computed from this value decreased much more steeply with increasing molecular dimension than the measured clearances, suggesting a highly significant contribution by filtration despite the very large diffusional gradients that existed under the experimental conditions. The results indicate that the size selectivity of the hemochorial embryo placenta in vivo is not very significant, and that under normal conditions filtrate of maternal plasma constitutes a major contributor to embryonic supply.
The American journal of physiology 12/1993; 265(5 Pt 2):H1804-8.
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ABSTRACT: A proposed convention sets zero pressure at atmospheric pressure at the level of the surface supporting the supine patient and takes the cm of water as the unit of measurement. This ensures that measurements made in different clinics will be comparable. Statements about 'higher' and 'lower' pressures, in different patients or in the same patient in different situations, should specify the level of the uterus to which the statement applies.
European Journal of Obstetrics & Gynecology and Reproductive Biology 01/1993; 47(3):181-4. · 1.97 Impact Factor
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ABSTRACT: Uterine renin may regulate uteroplacental blood flow locally through changes in vascular resistance or systemically by supporting arterial blood pressure. Captopril (5 mg/kg) was given i.v. to 14 conscious pregnant rabbits at day 27.5 +/- 0.3 of gestation for the purpose of investigating the effects of angiotensin converting enzyme inhibition on uteroplacental blood flow and oxygen consumption. Control measurements (mean +/- S.E.M.) were compared to measurements made at 1 hr (n = 14) and at 3 to 4 hr (n = 7). Arterial blood pressure decreased from 80 +/- 3 to 66 +/- 3 mm Hg, P less than .01, and then declined further to 56 +/- 4 mm Hg, P less than .01. Cardiac output was unchanged at 1 hr, 799 +/- 79 vs. 705 +/- 61 ml/min, but was decreased to 634 +/- 29 ml/min by 3 to 4 hr, P less than .01. There was no change in renal blood flow from 102 +/- 13 ml/min. Total uterine blood flow decreased from 37 +/- 5 to 29 +/- 5 ml/min, P less than .01, and then to 23 +/- 1 ml/min, P less than .01, whereas placental blood flow decreased from 25 +/- 4 to 19 +/- 3 to 15 +/- 3 ml/min, P less than .01; there was no significant change in myoendometrial flow. Oxygen delivery per uterine horn decreased from 2.4 +/- 0.3 to 1.8 +/- 0.4 to 1.6 +/- 0.2 ml/min, P less than .005. Oxygen consumption per horn decreased from 1.31 +/- 0.14 to 1.05 +/- 0.15 ml/min by 1 hr, P less than .05, and there was no further decrease.(ABSTRACT TRUNCATED AT 250 WORDS)
Journal of Pharmacology and Experimental Therapeutics 02/1992; 260(1):294-9. · 3.83 Impact Factor
