Ontogeny of single glomerular perfusion rate in fetal and newborn lambs.
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Biomedical subjects
Publications and source records attributed to J E Robillard.
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Transport of bicarbonate (HCO3-) was studied in segments of the jejunum and ileum in two-, three-, and eight-wk-old rats using and in vivo, one-pass perfusion technique. From isotonic solutions the net absorption of HCO3-(/B5mol/hr/g dry wt) in the jejunal segments was about twice as gret (P-0.01) in the two- and three- as in the eight-wk-old rats. In ileal segments, HCO3-transport was quite variable; in the two- and three-wk-old rats, there was net absorption, whereas in the eight-wk-old rats, there was net secretion. In both segments, net absorption was unaffected by addition of glucose (5 mmoles/liter), or acetazolamide (10 mmoles/liter) to the perfusion solution. Perfusion of a hypertonic old rats induced metabolic acidosis, which was associated with net secretion of relatively large amounts of bicarbonate into the lumen of both segments. Perfusion of the hypertonic solution in the eight-wk-old rats did not change blood acid-base status. In these rats, net absorption of bicarbonate in the jejunum was decreased, and net secretion in the ileum was enhanced in comparison to values noted during perfusion of the isotonic solution.
The renal response to endogenous aldosterone production at different times during gestation and immediately after birth, as well as factors controlling aldosterone secretion during fetal life have been studied in 34 lamb fetuses (106-142 days of gestation, term 145 days) and in 6 newborn lambs (3-8 days postnatal age). It was demonstrated that the increase in fetal plasma aldosterone concentrations correlated with the increase in fetal plasma renin activity (PRA) (r = 0.67, p < 0.001). Moreover, it was fond that the slope of the regression line between plasma aldosterone and PRA during fetal life was significantly steeper (p < 0.05) than after birth. Significant correlation coefficients were found between the fetal urinary to plasma ratios (U/P) of sodium over potassium [(U/P)Na+/(U/P)K+] and either fetal plasma aldosterone (r = -0.53, p < 0.005) or fetal age (r = -0.52, p < 0.005). Moreover, in 7 out of 9 fetuses over 125 days, frank secretion of potassium by the fetal tubular cells was demonstrated; such a secretion was present in only 1 of the 15 fetuses between 101 and 125 days of gestation. Finally, it was demonstrated that the increase in mean arterial blood pressure during fetal life and after birth is not a major factor in the increase in fetal glomerular filtration rate during gestation or in the adaptation of glomerular filtration rate to extrauterine life.
Increases in the maternal-fetal pH gradient that may occur during labor and delivery may increase the fetal concentration of local anesthetics. The authors evaluated effects of pH changes on the transplacental concentration equilibrium of bupivacaine. They increased the maternal-fetal pH gradient in each of six pregnant ewes from a control value of 0.15 to 0.54 by hyperventilating the lungs of the ewe and infusing lactic acid into her fetus. After infusion of bupivacaine, 0.15 mg/kg, intravenously into the mother, the drug rapidly appeared in fetal blood, with values significantly increased over control values at 1 and 5 min. The fetal/maternal (f/m) ratios were increased significantly at 5, 15, and 30 min. The f/m ratios had stabilized by 15 min in both control and experimental states, suggesting that equilibrium had been achieved. The consistently low f/m ratios are explained by the presumed similarity of the ovine maternal and fetal protein binding rates to those of man. It is concluded that the maternal and fetal pH values are major factors in the determination of the f/m ratios.
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In order to investigate the metabolic effects of a constant hypertonic glucose infusion in well-oxygenated fetuses, ten experiments were carried out in nine long-term experiments in fetal lambs. It appeared that a constant hypertonic glucose infusion did not significantly affect the fetal blood gases, pH, and plasma lactate levels when fetal glucose was kept below 150 mg. per 100 ml. It was also demonstrated that glucose infusions significantly increased the fetal lactate levels and decreased the blood pH when fetal plasma glucose was over 150 mg. per 100 ml. However, there was no decrease in fetal PO2 and pco2 until fetal glucose reached values over 300 mg. per 100 ml. These studies suggest that constant hypertonic glucose infusion does not improve fetal blood gases or pH and that fetal hyperglycemia over 300 mg. per 100 ml. produces severe metabolic acidosis.
Studies were carried out during fetal life in sheep to determine the relationship of 2,3-diphosphoglycerate (DPG), the intracellular red cell and extracellular pH, and the switchover to adult hemoglobin synthesis in regulating the position of the fetal red cell oxygen-affinity curve in utero. Adult hemoglobin first appeared near 120 days of gestation. The mean oxygen tension at which hemoglobin is half saturated (P50) prior to 120 days of gestation remained constant at 13.9 +/- 0.3 (SD) Torr and then increased gradually as gestation continued, reaching 19 Torr at term. During the interval of fetal life studied, the level of DPG was 4.43 +/- 1.63 (SD) micromol/g Hb and the deltapH between plasma and red blood cells was 0.227 +/- 0.038 (SD); neither was affected by gestational age. The decrease in the red cell oxygen affinity after 120 days of gestation ocrrelated with the amount of adult hemoglobin present in the fetus (r = 0.78; P less than 0.001). This decrease can be attributed only to the amount of the adult-type hemoglobin present, and not to DPG, or to changes in the deltapH between plasma and red blood cells, because both remained stable during the last trimester.
The capacity of the fetal renal carbonic enzyme to facilitate the renal reabsorption of bicarbonate was studied in 8 long-term fetal lamb preparations (103-124 days of gestation). After acetazolamide administration the fetal arterial blood pH and PCO2 values decreased significantly (p less than 0.05). Significant increases in fetal urinary pH (p less than 0.001), and urinary excretion of bicarbonate (p less than 0.001), potassium (p less than 0.05) and total cation (Na+ + K+) were observed after carbonic anhydrase inhibition. It is suggested from these in vivo studies that renal carbonic anhydrase is present and active during fetal life and does not limit the capacity of the fetal kidney to reabsorb bicarbonate.
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The maturation of the glomerular filtration rate (GFR) and the interrelationship between the GFR and the renal transport of sodium and chloride have been evaluated during the last trimester of gestation with the use of long-term experiments in fetal lambs. An increase in GFR (milliliters per minute) parallel to the increase in fetal body weight was demonstrated; however, no significant change was shown when the GFR (milliliters per minute per kilogram of fetal body weight) (1.141 +/- 0.079) was related to fetal body weight or gestational age. There was a constant increase in sodium and chloride reabsorption (microequivalents per minute) during the last third of gestation. This increase in sodium and chloride reabsorption was less than the increase in GFR (milliliters per minute) before 129 days but became higher than the rise of GFR (milliliters per minute) after 129 days of gestation.
In order to determine the renal threshold for bicarbonate in the fetal lamb and factors that may influence renal reabsorption of bicarbonate in the fetus, 18 acute fetal lamb preparations (110-140 days of gestation) were studied. In the first series of experiments involving nine fetuses, the renal bicarbonate threshold of normal fetuses varied from 12.0 to 23.5 mM/liter with a mean value of 17.7 +/- 1.37 mM/liter. This is significantly lower (P less than 0.005) than the value measured in five adult sheep of 28.7 +/- 1.68 mM/liter. There was a significant and positive correlation between the fetal plasma bicarbonate at threshold level and the fetal kidney weight, as well as fetal age. In a second series of experiments, the excretion of bicarbonate and sodium was studied in nine fetuses before and after dehydration by peritoneal dialysis. After peritoneal dialysis there was a significant decrease in urinary pH (P less than 0.025), bicarbonate excretion (P less than 0.001), sodium excretion (P less than 0.001), fractional excretion of sodium (P less than 0.01). When glucose was replaced by mannitol in the peritoneal dialysis fluid the effects on bicarbonate reabsorption paralleled those when glucose was present in dialysis fluid. It was also shown that when glucose was given intravenously to the fetus, up to a plasma concentration of 200 mg/100 ml, there was no effect on the fetal renal reabsorption of bicarbonate. These data indicate that the low threshold for bicarbonate reabsorption by the fetal kidney is not due to a limited capacity to increase bicarbonate or sodium reabsorption and suggest that the fetal kidney is able to respond to volume depletion by increasing its reabsorption in bicarbonate and electrolytes.
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Few data are available documenting the evolution of glomerular filtration rate (GFR) during gestation. In order to investigate this aspect, 33 fetal sheep have been studied, with the use of an intrauterine fetal preparation. It appears that the actual GFR (AGFR) in milliliters per minute increased during the last third of gestation without a significant increase in GFR expressed as milliliters per minute per kilogram of fetal weight (GFR-FW) and as milliliters per minute per gram of kidney weight (GFR-KW). It is suggested that a parallel and constant increase in AGFR and in total fetal weight or kidney weight might explain the absence of variation if GFR-FW or GFR-KW during the last third of gestation.
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