- Email: [email protected]
Fetal plasma and renal responses to ruminal fluid
Fetal plasma and renal responses to ruminal fluid Michael G. Ross, MD, Dan Sherman, MD, M. Gore Ervin, MD, James Homme, and Joy Gimpel Torrance and Los Angeles, California, and Zerifin, Israel Amniotic fluid homeostasis is dependent on a balance of fetal fluid production and absorption. The fetal gastrointestinal tract is believed to resorb 500 to 1000 ml of amniotic fluid per day during 7 to 1O bouts of swallowing activity. However, the impact of ruminal fluid on fetal plasma composition and fluid homeostasis is largely unknown. Seven ovine fetuses (120 ::+: 1 day) received intraruminal infusions of 0.9% or 3% saline solution on alternate days. In response to successive 40-minute intraruminal infusions of 0.9% saline solution (0.5 and 1.0 ml/kg/min), there was no change from basal levels of fetal plasma osmolality (295.7 ::+: 2.9 mosm), plasma arginine vasopressin (1.45 ::+: 0.29 pg/ml), urine osmolality (150 ::+: 8 mosm), or urine volume (0.49 ± 0.10 ml/min). In response to the 3% saline solution infusion, significant increases were noted in fetal plasma osmolality (295.4 ± 3.1 to 302.6 ± 2.6 mosm), plasma arginine vasopressin (1.77 ± 0.31to4.84 ± 0.79 pg/ml), and urine osmolality (157 ± 13 to 342 ± 25 mosm), whereas fetal urine volume significantly decreased (0.35 ± 0.05 to 0.15 ± 0.06 ml/min). These results indicate that hypertonic, but not isotonic, saline solution infusion into the fetal gastrointestinal tract may affect fetal plasma composition and urine production. Under conditions of significant plasma to luminal osmotic gradients, fetal gastrointestinal water and electrolyte transfer may be more rapid than can be compensated by either fetal renal function or placental equilibration. (AM J OBSTET GYNECOL 1988;159:1407-12.)
Key words: Ruminal fluid, fetal plasma osmolality, arginine vasopressin
There is a daily circulation of 500 to 1000 ml per day of amniotic fluid water in the near-term ovine or human fetus'-"; fluid is secreted by fetal urine and lung liquid production and is absorbed by fetal swallowing.'·' Fetal swallowing, as described in the ovine model, occurs primarily in bouts of swallowing activity, each bout accounting for 20 to 200 ml of ingested fluid.-' By nature of this large daily circulation, fetal swallowing appears capable of influencing fetal and amniotic fluid water balance. Amniotic fluid is hypotonic to fetal and maternal plasma during the third trimester, although gastric fluid is nearly isotonic, a result of pulmonary and amniotic fluid mixture in the posterior pharynx. Increased amniotic fluid osmolality may occur during maternal dehydration" or periods of chronically elevated fetal plasma arginine vasopressin (AVP) levels. 7 Thus the fetus may ingest a range of fluid tonicities during bouts of swallowing. Swallowed fluid is absorbed in the fetal
From the Departments of Obstetrics and Gynecology, HarborUniversity of California, Los Angeles Medical Center, Cedars-Sinai Medical Center, and Assaf-Harofe Medical Center. Supported in part by grants HD 00744 and HD 06335 from the National Institute of Child Health and Human Development and grant 5-590 from the March of Dimes Birth Defects Foundation. Presented in part at the Thirty-fifth Annual Meeting of the Society for Gynecologic Investigation, Baltimore, Maryland, March 1720, 1988. Reprint requests: Michael 'G. Ross, MD, Department of Obstetrics and Gynecology, Harbor-UCLA Medical Center, Research Building 1, 1124 W. Carson St., Torrance, CA 90502.
gastrointestinal tract, as fecal water generally is not passed prenatally. Smith et al." reported that intraruminal infusion of hypotonic, but not isotonic, solutions significantly alters fetal plasma composition. However, the effect of hypertonic solutions in the fetal gastrointestinal tract has not been examined. We studied the effect of isotonic and hypertonic intraruminal fluid administered to the ovine fetus in a volume equivalent to that during a bout of fetal swallowing. The results suggest a significant effect of gastric fluid on fetal plasma composition and urine production.
Methods Animals and operations. Seven RambouilletColumbia pregnant ewes with singleton fetuses were studied. Animals were housed indoors in individual steel study cages and acclimated to a lighting regimen of a 12-hour-light/ 12-hour-dark period. Both food (alfalfa pellets) and water were available ad libitum, except for the withholding of food during the 24-hour period immediately preceding operation. Surgical anesthesia, operative procedures, and recovery have been described previously. 7 Briefly, catheters were placed in the fetal dorsal hind limb vein and artery and threaded to the inferior vena cava and aorta, respectively. The fetal bladder was catheterized via a cystotomy and a catheter was placed in the amniotic cavity. In addition, a 2 cm transverse incision was made under the fetal left anterior costal margin. The fetal 1407
1408
Ross et al.
December 1988 Am J Obstet Gynecol
0.9% Saline
0.5
1.0
CONTROL ml/kg/min ml/kg/min
~
..J
3101 305
:g ~
300
::; <(
o::i; E
OBSERVATION
PLASMA OSMOLALITY
<(-
:IE
295
"'~
290
<(
PLASMA AVP
URINE VOLUME UJ
:IE :::>....J .~
0
0.81 0.6
E
> .... 0.4 UJ z - 0.2
e
;r :::>
0 -40
0
40
80
120
160
Tl ME (minutes)
Fig. I. Fetal plasma osmolality, plasma AVP, urine osmolality, and urine volume in response to intraruminal 0.9% saline solution.
rumen was identified and incised, and a Tygon catheter (inner diameter, 1.3 mm; outer diameter, 2.3 mm) with multiple ports was secured to the lining of the rumen by a purse-string suture. The fetal peritoneum and skin were closed around the ruminal catheter. The uterus, maternal fascia, and skin were closed in separate layers with sutures. The maternal femoral artery and vein in one leg were catheterized and the catheters were threaded to the aorta and inferior vena, respectively. All catheters were exteriorized to the maternal flank and placed in a cloth pouch sewn to the ewe. Animals were allowed a minimum of 5 days of postoperative recovery, during which time antibiotics (methicillin, chloramphenicol) were administered in the fetal and maternal veins and amniotic cavity. Experimental protocol. All experiments were performed on unanesthetized ewes standing in the same individual cages in which they were maintained. Fetal arterial blood pH values and urine osmolalities were assessed and studies were undertaken only if the fetal arterial pH was >7.35 and fetal urine osmolality was
<180 mosm. During an initial 60-minute equilibration period, the fetal bladder catheter was drained to gravity and each fetus received an intravenous injection of inulin labeled with tritium (15 µCi in 2 ml 0.9% saline solution). After the equilibration period, fetal urine was collected at 10-minute intervals. Six fetuses received a 0.9% saline solution infusion and five fetuses received a 3% saline solution infusion. Four fetuses underwent both studies on alternate days. The mean ( ± SEM) gestational age at the initiation of both studies was 120 ± 1 day. The studies were divided into a 40-minute basal period (time - 40 to 0), two 40minute intraruminal infusion periods (time 0 to + 40 and time + 40 to + 80), and a 100-minute postinfusion observation period (time + 80 to + 180). The isotonic saline solution study consisted of an intraruminal infusion of 0.9% saline solution at rates of 0.5 and 1.0 ml/kg/min during the first and second 40-minute infusion periods, respectively. Fetal blood samples (3.0 ml) were collected at -10 and 0 minutes of the basal period, with subsequent samples collected at + 30 and + 40 minutes (infusion period 1), + 70 and + 80 minutes (infusion period 2), and + 110, + 120, + 150, and + 180 minutes (observation period). The total volume of fetal blood withdrawn at each sampling was replaced with an equal volume of heparinized maternal blood withdrawn before the study. Maternal blood samples (3.0 ml) were collected at - 10 and 0 minutes of the basal period and at + 70 and + 80 minutes of final infusion period. On an alternate day, an identical study was performed except that the infusion of 0.9% saline solution was replaced with an equivalent volume of 3% saline solution. All infusion concentrations were based on estimated fetal body weight (FBW) from the formula: FBW (kg) = [0.096 x gestational age (days)] - 9.2228 as described by Robillard and Weitzman. 9 Blood samples were collected into iced tubes containing 10 µl of 15% potassium-ethylenediaminetetraacetic acid per milliliter blood, the hematocrit was determined in duplicate, and the sample was immediately centrifuged. Plasma osmolality, tritiated inulin activity, and sodium and potassium concentrations were measured in aliquots of the prepared plasma, and the remainder was stored at - 20° C until measurement of AVP concentration. An additional 0.5 ml of blood was collected into heparinized I ml syringes for immediate measurement of blood pH, Po 2 , and Pco 2 • Urine volume was measured and aliquots were assessed for osmolality, sodium and potassium concentration, and tritiated inulin activity. Fetal heart rate and arterial blood and amniotic cavity pressures were monitored continuously by means of a Beckman R-612 physiologic recorder (Beckman,
Fetal response to ruminal fluid
Volume 159 Number 6
Palo Alto, Calif.) with Statham P23 transducers (Gould Inc., Oxnard, Calif.). Fetal blood pressure was corrected for amniotic fluid pressure. Analytic methods. Plasma AVP levels were measured by radioimmunoassay' 0 of 1 ml plasma samples extracted on Sep-Pak (Waters Associates, Milford, Mass.) columns. The extraction procedure of LaRochelle et al. 11 was modified to include 0.1 % trifluoroacetic acid in place of 4% acetic acid and sample elution was accomplished with 2 ml of a solution containing 50% methanol and 0.1 % trifluoroacetic acid. Synthetic AVP obtained from Bachem (Torrance, Calif.) was used as the standard. The AVP radioimmunoassay used in our laboratory is sensitive to 0.8 pg AVP per milliliter plasma (0.16 pg per tube) with 50% displacement of labeled ligand observed at plasma concentrations of 4 pg/ml. The intraassay and interassay coefficients of variation were 6% and 9%, respectively, with recovery of added synthetic AVP (lot no. R50015, Bachem) averaging 70%. Blood pH, Po2, and Pco 2 were measured at 39° C with a Radiometer Bm 33 MK 2-PHM 72 Mk2 acidbase analyzer system (Radiometer, Copenhagen, Denmark). Plasma and urine osmolalities were measured by freezing point depression on an Advanced Digimatic Osmometer (model MO, Advanced Instruments, Needham Heights, Mass.). Plasma and urine sodium and potassium concentrations were determined by flame photometry (model 143, Instrumentation Laboratory, Watertown, Mass.). The concentration of tritiated inulin in plasma and urine was assessed in a Beckman Ls-355 liquid scintillation counter (Beckman Instruments, Irvine, Calif.). Glomerular filtration rate was calculated as tritiated inulin clearance for each plasma sample and simultaneous urine collection. All values are expressed as the mean ± SEM. Values at time 0, + 40, + 80, and + 120 minutes represent the means of samples at - 10 and 0, + 30 and + 40, + 70 and + 80, and + 110 and + 120 minutes, respectively. Differences over time were assessed by repeatedmeasures analysis of variance with orthogonal decomposition. Linear, quadratic, or cubic trends in the data were considered statistically significant when the F test yielded a value of p < 0.05. Differences between time periods were determined by Dunnett's test. Results
In response to the intraruminal infusion of 0.9% saline solution to the fetus, there was no change from basal levels of fetal hematocrit (29.8% ± 2.1 %), pH (7.39 ± 0.01), Po2 (23.7 ± 1.4 mm Hg), Pco 2 (38.9 ± 2.3 mm Hg), systolic and diastolic blood pressure (54 ± 3 and 40 .± 3 mm Hg, respectively), and heart rate (181 ± 3 beats/min). Furthermore, there was no change from basal levels of fetal plasma
1409
3%Saline CONTROL
o. 5 ml/Kg/min
l.O ml/kg/min
OBSERVATION
IOl
3 305
300 PLASMA OSMOLAL/TY
295 290
~
>0
-
E
400l 300
:IE"' (/) 0 0
w
5
URINE OSMOLALITY
200
z
~
100
w
:IE
:::> _J
.~
''~
URINE VOLUME
0.4
o E 0.3 > .... w'E
z- 0.2
ii:
:::>
0.1 -40
0
40
BO
120
160
TIME (minutes)
Fig. 2. Fetal plasma osmolality, plasma AVP, urine osmolality, and urine volume in response to intraruminal 3% saline solution.
osmolality (295.7 ± 2.9 mosm), fetal plasma AVP (l.45 ± 0.29 pg/ml), urine osmolality (150 ± 8 mosm), and urine volume (0.49 ± 0.10 ml/min) (Fig. l). In addition, maternal hematocrit (32.4% ± 3.1 %), pH (7.41 ± O.Ol),Po2 (109 ± 5mmHg),Pco2 (29 ± 2mm Hg), and plasma osmolality (300.2 ± 3.0 mosm) did not change during the isotonic saline solution infusion to the fetus. In response to the intraruminal infusion of 3% saline solution to the fetus, there was a significant increase in fetal plasma osmolality (295.4 ± 3.1 to 302.6 ± 2.6 mosm; Fig. 2) and sodium concentration ( 146.8 ± 0.8 to 149.6 ± 2.2 mEq/L; Table I). Fetal plasma AVP concentrations increased from a basal level of 1. 77 ± 0.31 to 4.84 ± 0.79 pg/ml at the conclusion of the study (Fig. 2). There was no change from basal levels of fetal hematocrit, pH, Po 2, Pco 2, heart rate, and systolic and diastolic blood pressure (Table I). Fetal urine osmolality significantly increased from a basal value of 157 ± 13 mosm to a maximum of 342 ± 25 mosm whereas urine volume decreased from
December l 988 Am .J Obstet Gynecol
1410 Ross et al.
Table I. Fetal arterial values during basal period (time 0), intraruminal infusion of 3% saline solution (40 and 80 minutes), and observation period (120, 150, and 180 minutes) TimeO
Hematocrit (%) pH Po 2 (mm Hg) Pco 2 (mm Hg) Heart rate (beats/min) Plasma sodium (mEq/L) Plasma potassium (mEq/L) Systolic pressure (mm Hg) Diastolic pressure (mm Hg)
29.l 7.37 24.3 39.0 177
± ± ± ± ±
2.3 0.01 1.0 2.5 3
40 min
29.4 7.38 24.0 37.8 175
± ± ± ± ±
2.2 0.01 1.7 2.6 6
80 min
29.7 7.38 25.4 38.8 179
± ± ± ± ±
2.4 0.02 0.9 2.6 II
120 min
29.1 7.36 23.6 38.8 192
± ± ± ± ±
2.6 0.01 1.6 2.5 14
146.8 ± 0.8
146.9 ± 0.8
147.8 ± 1.4
148.4 ± 2.0
3.6 ± 0.1
3.5 ± 0.1
3.4 ± 0.1
47.5 ± 2.7
45.3 ± 2.6
31.4 ± 2.2
30.8 ± 2.1
150 min
29.2 7.36 23.9 39.0 189
± ± ± ± ±
2.6 0.01 1.0 2.1 15
180 min
29.1 7.35 23.8 38.2 176
± ± ± ± ±
2.4 0.01 0.9 1.9 6
150.2 ± 1.6*
149.6 ± 2.2*
3.4 ± 0.1
3.4 ± 0.1
3.4 ± 0.1
49.0 ± 3.5
49.8 ± 3.9
47.5 ± 3.4
48.6 ± 3.6
31.5 ± 2.8
32.3 ± 3.4
31.5 ± 3.0
31.6 ± 3.0
*p < 0.05 versus Time 0.
0.35 ± 0.05 ml/min to a minimum of 0.15 ± 0.06 ml/ min (Fig. 2). Although urine sodium and potassium concentrations significantly increased (Table II) and free water clearance significantly decreased, there was no change in osmolar clearance or fetal glomerular filtration rate (Table II). In response to the fetal infusion of 3% saline solution, maternal hematocrit (29.4% ± 3.1 %), pH (7.43 ± 0.03), Po 2 (99 ± 2 mm Hg),Pco 2 (28 ± 2 mm Hg), plasma osmolality (300.2 ± 3.2 mosm), and plasma AVP (3.4 ± 2.0 pg/ml) levels did not change.
Comment Although the fetus inevitably acquires net water and electrolytes from the maternal compartment, the daily ingestion of amniotic fluid may result in the absorption of nearly 1000 ml of water and 300 mEq of electrolytes near term. 1· 5 Intermittent swallowing of salivary and pulmonary secretions apparently occurs throughout a daily cycle. However, the majority of amniotic fluid is ingested in 2 to 10 bouts of daily swallowing activity.'· 5 The acute absorption of this fluid may have significant impact on fetal plasma composition and the subsequent regulation of fluid balance. Gastrointestinal absorption of water occurs passively, secondary either to osmotic gradients or to active transport of solutes and ions. In the mature gut there is close correlation between the membrane characteristics at each level of the intestine and the major type of water and solute transport in that region. "Leaky" epithelial membranes, which demonstrate low electrical potential differences, transfer water and solutes secondary to osmotic and concentration gradients, respectively. "Tight" epithelia, which demonstrate considerable electrical potential differences across the mucosa, actively absorb sodium, establishing a hyperosmolar compartment within the mucosa as the driving force for water
absorption. Whereas bidirectional water transfer may occur in leaky epithelia, unidirectional mucosa! to serosal flux predominates in the tight epithelia. 12 In the adult the proximal small intestine acts as leaky epithelium with the ileum and colon demonstrating tight membrane characteristics. This pattern is established by midgestation in the human fetal intestine. 13 The early gestation ovine fetal intestinal membranes are leaky, with electrical potential differences developing at 80 days in the abomasum and 120 days in the small intestine and colon. 14 Ovine fetal rumen characteristics are unknown. However, studies in the adult suggest that ruminal absorption of fluids and electrolytes is minimal when ruminal contents are isoosmotic with plasma. With increasing osmotic gradients across the rumen wall, transruminal fluid fluxes may occur in either direction. 15 In the present study there was no discernible impact of an intraruminal infusion of 0.9% saline solution on fetal plasma parameters or renal function, consistent with the report of Smith et al. 8 When dosages of isotonic saline solution similar to those used in the present study are infused intravenously rather than intraruminally to the ovine fetus, plasma volume expansion and a significant urinary diuresis are observed. 16 The lack of change in fetal hematocrit in the present study, as compared with the decrease associated with intravenous infusions, suggests that fetal plasma volume did not change. Thus it appears that absorption of isotonic gastrointestinal fluid occurred slowly, was compensated by transplacental or interstitial fluid flux, or was delayed beyond the observation period. The 3% saline solution infusion likely created significant ruminal hypertonicity. Although studies 17 in dogs have demonstrated that osmolalities
Fetal response to ruminal fluid
Volume 159 Number 6
1411
Table II. Fetal renal responses during basal period (time 0), intraruminal infusion of 3% saline solution (40 and 80 minutes), and observation period (120, 150, and 180 minutes) TimeO Glomerular filtra3.09 ± tion (ml/min) Urine sodium 37.2 ± (mEq/L) Urine potassium 2.15 ± (mEq/L) Free water clear0.179 ± ance (ml/min) Osmolar clearance 0.188 ± (ml/min)
40 min
80 min
120 min
150 min
180 min
2.78 ± 0.47
2.62 ± 0.63
0.42
2.79 ± 0.38
2.85 ± 0.53
2.41 ± 0.42
6.5
41.2 ± 7.3
50.2 ± 8.5
90.6 ± 13.5*
93.0 ± 9.7*
91.2 ± 4.0*
0.16
2.26 ± 0.38
2.46 ± 0.37
4.80 ± 0.76*
4.46 ± 1.14*
3.66 ± 1.15
0.030 0.141 ± 0.042
0.091 ± 0.024*
- 0.009 ± 0.008*
- 0.005 ± 0.002*
0.007 ± 0.003
0.206 0.168 ± 0.027
0.169 ± 0.035
0.182 ± 0.040
0.204 ± 0.033
0.195 ± 0.044
*P < 0.05 versus Time 0.
the rat may cause an increase in intraluminal water diffusion and mucosa! damage. 18· 19 However, these osmolalities may not be uncommon in ruminants; in adult sheep the osmolality of ruminal contents can increase threefold or more after meals of easily digestible carbohydrates.20 Thus the hypertonicity of the saline solution may be within the physiologic range of the adult rumen. Notably, the rumen of the ovine fetus at 128 days' gestation has been demonstrated to contain a keratinized epithelium, similar to that of the adult. 21 The intraruminal administration of 3% saline solution resulted in a significant increase in fetal plasma osmolality and sodium concentration. Although the actual site of fluid and electrolyte transfer within the gastrointestinal tract cannot be determined from this study, either gastrointestinal sodium was absorbed or plasma water was secreted into the gastrointestinal tract in response to luminal hypertonicity. The present results indicate an apparent preservation of plasma volume, as evidenced by the stable fetal hematocrit and the maintenance of glomerular filtration rate. Thus it is unlikely that significant plasma water entered the fetal gastrointestinal tract. However, active transport of sodium from rumen contents to blood has been demonstrated.21 Thus the data suggest that sodium absorption from the rumen or small intestine accounted for the increased plasma osmolality. Tows to less et al. 22 have demonstrated that placental water transfer is the major determinant of plasma osmolality in the ovine fetus; fetal kidneys compensate minimally for acute alterations in fetal water homeostasis. The present data indicate that ovine fetal gastrointestinal water and electrolyte transfer may be more rapid after ruminal infusion of hypertonic saline (-1000 mosm) than can be compensated by either fetal renal function or placental equilibration. The increase in fetal plasma osmolality was sufficient to stimulate fetal AVP secretion. In adult mammals AVP secretion generally occurs in response to a 2% increase from basal plasma osmolality. 23 In the present study a
significant increase in fetal plasma AVP occurred in response to only a 1% change in plasma osmolality. It is unlikely that plasma osmolality thresholds for AVP secretion are more sensitive in the fetus at 120 days' gestation than in the adult. 6 However, it is possible that resorption of hypertonic fluid in the gastrointestinal tract stimulated local hepatoportal osmoreceptors involved in AVP secretion. 24 Vasopressin stimulation resulted in the expected increase in urine osmolality and sodium and potassium concentrations and in decreases in urine volume and free water clearance. Consistent with AVP action, there was no significant alteration in glomerular filtration rate, with preservation of osmolar clearance. Thus, despite the significant gastrointestinal osmolar load, the urinary excretion of electrolytes was not increased in the fetus; placental transfer or perhaps the interstitial space likely accommodates the increased fetal body sodium. Amniotic fluid is hypotonic to fetal plasma in the basal state. However, increased amniotic fluid osmolality may occur during maternal dehydration 6 or periods of chronically elevated levels of fetal plasma AVP.' Previously we demonstrated that intraamniotic AVP may be recirculated to the fetus, presumably by swallowing; this results in increased plasma AVP levels and urinary hyperosmolality. 25 The current study suggests that fetal swallowing of hyperosmolar amniotic fluid may stimulate fetal AVP secretion, urinary hyperosmolality, and thus perhaps a further increase in amniotic fluid osmolality and AVP concentration. In summary, fetal bouts of swallowing of isotonic fluid may have little short-term impact on fetal plasma composition or urinary function. Slow absorption of gastrointestinal fluid or placental compensation for fluid resorption thus may serve to assure stable rates of fetal urine flow. The intraruminal administration of hypertonic fluid, however, has significant impact on fetal plasma osmolality, AVP secretion, and urine production. Although transplacental water and electrolyte
1412
Ross et al.
equilibration generally maintains fetal plasma homeostasis, the present data indicate that alterations in ovine fetal plasma composition as a result of gastrointestinal absorption may occur more rapidly than may be compensated by placental exchange. This observation suggests that fetal swallowing may influence amniotic fluid homeostasis by both absorption of fluid and subsequent regulation of production. We are grateful to Glenda Calvario for technical assistance and Sharon Schuler for manuscript preparation. REFERENCES 1. Abramovich DR, Garden A, Jandial L, et al. Fetal swallowing and voiding in relation to hydramnios. Obstet Gynaecol 1979;54: 15-20. 2. Gitlin D, Kumate J, Morales C, et al. The turnover of amniotic fluid protein in the human conceptus. AM J OBSTET GYNECOL 1972; 113:632-45. 3. Tomada S, Brace RA, Longo LD. Fate of labeled albumin and erythrocytes following injection into amniotic cavity of sheep. Amj Physiol 1986;251:R781-6. 4. Bradley RM, Mistretta CM. Swallowing in fetal sheep. Science 1973;179:1016-7. 5. Harding R, Bocking AD, Sigger JH, et al. Composition and volume of fluid swallowed by fetal sheep. Q J Exp Physiol 1984;69:487-95. 6. Bell RJ, Congiu M, Hardy KJ, et al. Gestation dependent aspects of the response of the ovine fetus to the osmotic stress induced by maternal water deprivation. Q J Exp Physiol 1984;69: 187-95. 7. Ross MG, Ervin MG, Leake RD, et al. Amniotic fluid ionic concentration in response to chronic fetal vasopressin infusion. Amj Physiol 1985;157:1292-7. 8. Smith FG, Lumbers ER, Kesby GJ. The renal response to the ingestion of fluid by the fetal sheep. J Dev Physiol I 986;8:259-66. 9. Robillard JR, Weitzman RE. Developmental aspects of the fetal renal response to exogenous arginine vasopressin. Am] Physiol 1980;238:F407-14. 10. Weitzman RE, Reviczky A, Oddie TH, et al. Effect of osmolality on arginine vasopressin and renin release after hemorrhage. Am J Physiol 1980;238:E62-8.
December 1988 Am J Obstet Gynecol
11. LaRochelle ET, Stem P, North WG. A new extraction of arginine vasopressin from blood: the use of octadecasilylsilica. Pflugers Arch Eur J Physiol 1980;387:79-81. 12. Kaiser MH. Water and mineral transport. In: JE Berk, ed. Bockus gastroenterology, Philadelphia: WB Saunders, 1985: 1538-52. 13. Levin RJ, Koldovsky 0, Hoskovaj, et al. Electrical activity across human foetal small intestine associated with absorption processes. Gut 1968;9:206-13. 14. Wright GH, Nixon DA. Absorption of amniotic fluid in the gut of the foetal sheep. Nature 1961; 190:816. 15. Warner ACI, Stacy BD. Water, sodium, and potassium movements across the rumen wall of sheep. QJ Exp Physiol 1972;57: 103-19. 16. Ross MG, Ervin MG, Lam RW, et al. Plasma atrial natriuretic peptide response to volume expansion in the ovine fetus. AMJ OBSTET GYNECOL 1987;157:1292-7. 17. Kvietys PR, Pittman R, Chou CC. Contribution of luminal concentration of nutrients and osmolality of postprandial intestinal hyperemia in dogs. Proc Soc Exp Biol Med 1976; 152:659-63. 18. Johnson L, Nordstrom H, Nylander G. Experimental studies on fluid pathophysiology in small intestinal obstruction in the rat. I. Effects of intraluminal hyperosmolality. Scand J Gastroenterol 1978; 13:49-56. 19. Teichberg S, Lifshitz F, Pergolizzi R, Wapnir RA. Response of rat intestine to a hyperosmotic feeding. Pediatr Res 1978; 12:720-5. 20. Engelhardt WV. Movement of water across the rumen epithelium. In: Phillipson AT, ed. Physiology of digestion and metabolism in the ruminant. Boston: Oriel Press, 1969: 132-46. 21. Steven DH, Marshall AB. Organization of the rumen epithelium. In: Phillipson AT, ed. Physiology of digestion and metabolism in the ruminant. Boston: Oriel Press, 1969:80-100. 22. Towstoless MK, Congiu M, Coghl~n JP, et al. Placental and renal control of plasma osmolality in chronically cannulated ovine fetus. Am J Physiol 1987;253:R389-95. 23. Berl T, Anderson RJ, McDonald KM, et al. Clinical disorders of water metabolism. Kidney Int 1976;10:117-32. 24. Baertschi AJ, Massy Y, Kwon S. Vasopressin responses to peripheral and central osmotic pulse stimulation. Peptides 1985;6:1131-5. 25. Ervin MG, Ross MG, Leake RD, et al. Fetal recirculation of amniotic fluid arginine vasopressin. Am J Physiol I 986;250:E253-8.
Key words: Ruminal fluid, fetal plasma osmolality, arginine vasopressin
There is a daily circulation of 500 to 1000 ml per day of amniotic fluid water in the near-term ovine or human fetus'-"; fluid is secreted by fetal urine and lung liquid production and is absorbed by fetal swallowing.'·' Fetal swallowing, as described in the ovine model, occurs primarily in bouts of swallowing activity, each bout accounting for 20 to 200 ml of ingested fluid.-' By nature of this large daily circulation, fetal swallowing appears capable of influencing fetal and amniotic fluid water balance. Amniotic fluid is hypotonic to fetal and maternal plasma during the third trimester, although gastric fluid is nearly isotonic, a result of pulmonary and amniotic fluid mixture in the posterior pharynx. Increased amniotic fluid osmolality may occur during maternal dehydration" or periods of chronically elevated fetal plasma arginine vasopressin (AVP) levels. 7 Thus the fetus may ingest a range of fluid tonicities during bouts of swallowing. Swallowed fluid is absorbed in the fetal
From the Departments of Obstetrics and Gynecology, HarborUniversity of California, Los Angeles Medical Center, Cedars-Sinai Medical Center, and Assaf-Harofe Medical Center. Supported in part by grants HD 00744 and HD 06335 from the National Institute of Child Health and Human Development and grant 5-590 from the March of Dimes Birth Defects Foundation. Presented in part at the Thirty-fifth Annual Meeting of the Society for Gynecologic Investigation, Baltimore, Maryland, March 1720, 1988. Reprint requests: Michael 'G. Ross, MD, Department of Obstetrics and Gynecology, Harbor-UCLA Medical Center, Research Building 1, 1124 W. Carson St., Torrance, CA 90502.
gastrointestinal tract, as fecal water generally is not passed prenatally. Smith et al." reported that intraruminal infusion of hypotonic, but not isotonic, solutions significantly alters fetal plasma composition. However, the effect of hypertonic solutions in the fetal gastrointestinal tract has not been examined. We studied the effect of isotonic and hypertonic intraruminal fluid administered to the ovine fetus in a volume equivalent to that during a bout of fetal swallowing. The results suggest a significant effect of gastric fluid on fetal plasma composition and urine production.
Methods Animals and operations. Seven RambouilletColumbia pregnant ewes with singleton fetuses were studied. Animals were housed indoors in individual steel study cages and acclimated to a lighting regimen of a 12-hour-light/ 12-hour-dark period. Both food (alfalfa pellets) and water were available ad libitum, except for the withholding of food during the 24-hour period immediately preceding operation. Surgical anesthesia, operative procedures, and recovery have been described previously. 7 Briefly, catheters were placed in the fetal dorsal hind limb vein and artery and threaded to the inferior vena cava and aorta, respectively. The fetal bladder was catheterized via a cystotomy and a catheter was placed in the amniotic cavity. In addition, a 2 cm transverse incision was made under the fetal left anterior costal margin. The fetal 1407
1408
Ross et al.
December 1988 Am J Obstet Gynecol
0.9% Saline
0.5
1.0
CONTROL ml/kg/min ml/kg/min
~
..J
3101 305
:g ~
300
::; <(
o::i; E
OBSERVATION
PLASMA OSMOLALITY
<(-
:IE
295
"'~
290
<(
PLASMA AVP
URINE VOLUME UJ
:IE :::>....J .~
0
0.81 0.6
E
> .... 0.4 UJ z - 0.2
e
;r :::>
0 -40
0
40
80
120
160
Tl ME (minutes)
Fig. I. Fetal plasma osmolality, plasma AVP, urine osmolality, and urine volume in response to intraruminal 0.9% saline solution.
rumen was identified and incised, and a Tygon catheter (inner diameter, 1.3 mm; outer diameter, 2.3 mm) with multiple ports was secured to the lining of the rumen by a purse-string suture. The fetal peritoneum and skin were closed around the ruminal catheter. The uterus, maternal fascia, and skin were closed in separate layers with sutures. The maternal femoral artery and vein in one leg were catheterized and the catheters were threaded to the aorta and inferior vena, respectively. All catheters were exteriorized to the maternal flank and placed in a cloth pouch sewn to the ewe. Animals were allowed a minimum of 5 days of postoperative recovery, during which time antibiotics (methicillin, chloramphenicol) were administered in the fetal and maternal veins and amniotic cavity. Experimental protocol. All experiments were performed on unanesthetized ewes standing in the same individual cages in which they were maintained. Fetal arterial blood pH values and urine osmolalities were assessed and studies were undertaken only if the fetal arterial pH was >7.35 and fetal urine osmolality was
<180 mosm. During an initial 60-minute equilibration period, the fetal bladder catheter was drained to gravity and each fetus received an intravenous injection of inulin labeled with tritium (15 µCi in 2 ml 0.9% saline solution). After the equilibration period, fetal urine was collected at 10-minute intervals. Six fetuses received a 0.9% saline solution infusion and five fetuses received a 3% saline solution infusion. Four fetuses underwent both studies on alternate days. The mean ( ± SEM) gestational age at the initiation of both studies was 120 ± 1 day. The studies were divided into a 40-minute basal period (time - 40 to 0), two 40minute intraruminal infusion periods (time 0 to + 40 and time + 40 to + 80), and a 100-minute postinfusion observation period (time + 80 to + 180). The isotonic saline solution study consisted of an intraruminal infusion of 0.9% saline solution at rates of 0.5 and 1.0 ml/kg/min during the first and second 40-minute infusion periods, respectively. Fetal blood samples (3.0 ml) were collected at -10 and 0 minutes of the basal period, with subsequent samples collected at + 30 and + 40 minutes (infusion period 1), + 70 and + 80 minutes (infusion period 2), and + 110, + 120, + 150, and + 180 minutes (observation period). The total volume of fetal blood withdrawn at each sampling was replaced with an equal volume of heparinized maternal blood withdrawn before the study. Maternal blood samples (3.0 ml) were collected at - 10 and 0 minutes of the basal period and at + 70 and + 80 minutes of final infusion period. On an alternate day, an identical study was performed except that the infusion of 0.9% saline solution was replaced with an equivalent volume of 3% saline solution. All infusion concentrations were based on estimated fetal body weight (FBW) from the formula: FBW (kg) = [0.096 x gestational age (days)] - 9.2228 as described by Robillard and Weitzman. 9 Blood samples were collected into iced tubes containing 10 µl of 15% potassium-ethylenediaminetetraacetic acid per milliliter blood, the hematocrit was determined in duplicate, and the sample was immediately centrifuged. Plasma osmolality, tritiated inulin activity, and sodium and potassium concentrations were measured in aliquots of the prepared plasma, and the remainder was stored at - 20° C until measurement of AVP concentration. An additional 0.5 ml of blood was collected into heparinized I ml syringes for immediate measurement of blood pH, Po 2 , and Pco 2 • Urine volume was measured and aliquots were assessed for osmolality, sodium and potassium concentration, and tritiated inulin activity. Fetal heart rate and arterial blood and amniotic cavity pressures were monitored continuously by means of a Beckman R-612 physiologic recorder (Beckman,
Fetal response to ruminal fluid
Volume 159 Number 6
Palo Alto, Calif.) with Statham P23 transducers (Gould Inc., Oxnard, Calif.). Fetal blood pressure was corrected for amniotic fluid pressure. Analytic methods. Plasma AVP levels were measured by radioimmunoassay' 0 of 1 ml plasma samples extracted on Sep-Pak (Waters Associates, Milford, Mass.) columns. The extraction procedure of LaRochelle et al. 11 was modified to include 0.1 % trifluoroacetic acid in place of 4% acetic acid and sample elution was accomplished with 2 ml of a solution containing 50% methanol and 0.1 % trifluoroacetic acid. Synthetic AVP obtained from Bachem (Torrance, Calif.) was used as the standard. The AVP radioimmunoassay used in our laboratory is sensitive to 0.8 pg AVP per milliliter plasma (0.16 pg per tube) with 50% displacement of labeled ligand observed at plasma concentrations of 4 pg/ml. The intraassay and interassay coefficients of variation were 6% and 9%, respectively, with recovery of added synthetic AVP (lot no. R50015, Bachem) averaging 70%. Blood pH, Po2, and Pco 2 were measured at 39° C with a Radiometer Bm 33 MK 2-PHM 72 Mk2 acidbase analyzer system (Radiometer, Copenhagen, Denmark). Plasma and urine osmolalities were measured by freezing point depression on an Advanced Digimatic Osmometer (model MO, Advanced Instruments, Needham Heights, Mass.). Plasma and urine sodium and potassium concentrations were determined by flame photometry (model 143, Instrumentation Laboratory, Watertown, Mass.). The concentration of tritiated inulin in plasma and urine was assessed in a Beckman Ls-355 liquid scintillation counter (Beckman Instruments, Irvine, Calif.). Glomerular filtration rate was calculated as tritiated inulin clearance for each plasma sample and simultaneous urine collection. All values are expressed as the mean ± SEM. Values at time 0, + 40, + 80, and + 120 minutes represent the means of samples at - 10 and 0, + 30 and + 40, + 70 and + 80, and + 110 and + 120 minutes, respectively. Differences over time were assessed by repeatedmeasures analysis of variance with orthogonal decomposition. Linear, quadratic, or cubic trends in the data were considered statistically significant when the F test yielded a value of p < 0.05. Differences between time periods were determined by Dunnett's test. Results
In response to the intraruminal infusion of 0.9% saline solution to the fetus, there was no change from basal levels of fetal hematocrit (29.8% ± 2.1 %), pH (7.39 ± 0.01), Po2 (23.7 ± 1.4 mm Hg), Pco 2 (38.9 ± 2.3 mm Hg), systolic and diastolic blood pressure (54 ± 3 and 40 .± 3 mm Hg, respectively), and heart rate (181 ± 3 beats/min). Furthermore, there was no change from basal levels of fetal plasma
1409
3%Saline CONTROL
o. 5 ml/Kg/min
l.O ml/kg/min
OBSERVATION
IOl
3 305
300 PLASMA OSMOLAL/TY
295 290
~
>0
-
E
400l 300
:IE"' (/) 0 0
w
5
URINE OSMOLALITY
200
z
~
100
w
:IE
:::> _J
.~
''~
URINE VOLUME
0.4
o E 0.3 > .... w'E
z- 0.2
ii:
:::>
0.1 -40
0
40
BO
120
160
TIME (minutes)
Fig. 2. Fetal plasma osmolality, plasma AVP, urine osmolality, and urine volume in response to intraruminal 3% saline solution.
osmolality (295.7 ± 2.9 mosm), fetal plasma AVP (l.45 ± 0.29 pg/ml), urine osmolality (150 ± 8 mosm), and urine volume (0.49 ± 0.10 ml/min) (Fig. l). In addition, maternal hematocrit (32.4% ± 3.1 %), pH (7.41 ± O.Ol),Po2 (109 ± 5mmHg),Pco2 (29 ± 2mm Hg), and plasma osmolality (300.2 ± 3.0 mosm) did not change during the isotonic saline solution infusion to the fetus. In response to the intraruminal infusion of 3% saline solution to the fetus, there was a significant increase in fetal plasma osmolality (295.4 ± 3.1 to 302.6 ± 2.6 mosm; Fig. 2) and sodium concentration ( 146.8 ± 0.8 to 149.6 ± 2.2 mEq/L; Table I). Fetal plasma AVP concentrations increased from a basal level of 1. 77 ± 0.31 to 4.84 ± 0.79 pg/ml at the conclusion of the study (Fig. 2). There was no change from basal levels of fetal hematocrit, pH, Po 2, Pco 2, heart rate, and systolic and diastolic blood pressure (Table I). Fetal urine osmolality significantly increased from a basal value of 157 ± 13 mosm to a maximum of 342 ± 25 mosm whereas urine volume decreased from
December l 988 Am .J Obstet Gynecol
1410 Ross et al.
Table I. Fetal arterial values during basal period (time 0), intraruminal infusion of 3% saline solution (40 and 80 minutes), and observation period (120, 150, and 180 minutes) TimeO
Hematocrit (%) pH Po 2 (mm Hg) Pco 2 (mm Hg) Heart rate (beats/min) Plasma sodium (mEq/L) Plasma potassium (mEq/L) Systolic pressure (mm Hg) Diastolic pressure (mm Hg)
29.l 7.37 24.3 39.0 177
± ± ± ± ±
2.3 0.01 1.0 2.5 3
40 min
29.4 7.38 24.0 37.8 175
± ± ± ± ±
2.2 0.01 1.7 2.6 6
80 min
29.7 7.38 25.4 38.8 179
± ± ± ± ±
2.4 0.02 0.9 2.6 II
120 min
29.1 7.36 23.6 38.8 192
± ± ± ± ±
2.6 0.01 1.6 2.5 14
146.8 ± 0.8
146.9 ± 0.8
147.8 ± 1.4
148.4 ± 2.0
3.6 ± 0.1
3.5 ± 0.1
3.4 ± 0.1
47.5 ± 2.7
45.3 ± 2.6
31.4 ± 2.2
30.8 ± 2.1
150 min
29.2 7.36 23.9 39.0 189
± ± ± ± ±
2.6 0.01 1.0 2.1 15
180 min
29.1 7.35 23.8 38.2 176
± ± ± ± ±
2.4 0.01 0.9 1.9 6
150.2 ± 1.6*
149.6 ± 2.2*
3.4 ± 0.1
3.4 ± 0.1
3.4 ± 0.1
49.0 ± 3.5
49.8 ± 3.9
47.5 ± 3.4
48.6 ± 3.6
31.5 ± 2.8
32.3 ± 3.4
31.5 ± 3.0
31.6 ± 3.0
*p < 0.05 versus Time 0.
0.35 ± 0.05 ml/min to a minimum of 0.15 ± 0.06 ml/ min (Fig. 2). Although urine sodium and potassium concentrations significantly increased (Table II) and free water clearance significantly decreased, there was no change in osmolar clearance or fetal glomerular filtration rate (Table II). In response to the fetal infusion of 3% saline solution, maternal hematocrit (29.4% ± 3.1 %), pH (7.43 ± 0.03), Po 2 (99 ± 2 mm Hg),Pco 2 (28 ± 2 mm Hg), plasma osmolality (300.2 ± 3.2 mosm), and plasma AVP (3.4 ± 2.0 pg/ml) levels did not change.
Comment Although the fetus inevitably acquires net water and electrolytes from the maternal compartment, the daily ingestion of amniotic fluid may result in the absorption of nearly 1000 ml of water and 300 mEq of electrolytes near term. 1· 5 Intermittent swallowing of salivary and pulmonary secretions apparently occurs throughout a daily cycle. However, the majority of amniotic fluid is ingested in 2 to 10 bouts of daily swallowing activity.'· 5 The acute absorption of this fluid may have significant impact on fetal plasma composition and the subsequent regulation of fluid balance. Gastrointestinal absorption of water occurs passively, secondary either to osmotic gradients or to active transport of solutes and ions. In the mature gut there is close correlation between the membrane characteristics at each level of the intestine and the major type of water and solute transport in that region. "Leaky" epithelial membranes, which demonstrate low electrical potential differences, transfer water and solutes secondary to osmotic and concentration gradients, respectively. "Tight" epithelia, which demonstrate considerable electrical potential differences across the mucosa, actively absorb sodium, establishing a hyperosmolar compartment within the mucosa as the driving force for water
absorption. Whereas bidirectional water transfer may occur in leaky epithelia, unidirectional mucosa! to serosal flux predominates in the tight epithelia. 12 In the adult the proximal small intestine acts as leaky epithelium with the ileum and colon demonstrating tight membrane characteristics. This pattern is established by midgestation in the human fetal intestine. 13 The early gestation ovine fetal intestinal membranes are leaky, with electrical potential differences developing at 80 days in the abomasum and 120 days in the small intestine and colon. 14 Ovine fetal rumen characteristics are unknown. However, studies in the adult suggest that ruminal absorption of fluids and electrolytes is minimal when ruminal contents are isoosmotic with plasma. With increasing osmotic gradients across the rumen wall, transruminal fluid fluxes may occur in either direction. 15 In the present study there was no discernible impact of an intraruminal infusion of 0.9% saline solution on fetal plasma parameters or renal function, consistent with the report of Smith et al. 8 When dosages of isotonic saline solution similar to those used in the present study are infused intravenously rather than intraruminally to the ovine fetus, plasma volume expansion and a significant urinary diuresis are observed. 16 The lack of change in fetal hematocrit in the present study, as compared with the decrease associated with intravenous infusions, suggests that fetal plasma volume did not change. Thus it appears that absorption of isotonic gastrointestinal fluid occurred slowly, was compensated by transplacental or interstitial fluid flux, or was delayed beyond the observation period. The 3% saline solution infusion likely created significant ruminal hypertonicity. Although studies 17 in dogs have demonstrated that osmolalities
Fetal response to ruminal fluid
Volume 159 Number 6
1411
Table II. Fetal renal responses during basal period (time 0), intraruminal infusion of 3% saline solution (40 and 80 minutes), and observation period (120, 150, and 180 minutes) TimeO Glomerular filtra3.09 ± tion (ml/min) Urine sodium 37.2 ± (mEq/L) Urine potassium 2.15 ± (mEq/L) Free water clear0.179 ± ance (ml/min) Osmolar clearance 0.188 ± (ml/min)
40 min
80 min
120 min
150 min
180 min
2.78 ± 0.47
2.62 ± 0.63
0.42
2.79 ± 0.38
2.85 ± 0.53
2.41 ± 0.42
6.5
41.2 ± 7.3
50.2 ± 8.5
90.6 ± 13.5*
93.0 ± 9.7*
91.2 ± 4.0*
0.16
2.26 ± 0.38
2.46 ± 0.37
4.80 ± 0.76*
4.46 ± 1.14*
3.66 ± 1.15
0.030 0.141 ± 0.042
0.091 ± 0.024*
- 0.009 ± 0.008*
- 0.005 ± 0.002*
0.007 ± 0.003
0.206 0.168 ± 0.027
0.169 ± 0.035
0.182 ± 0.040
0.204 ± 0.033
0.195 ± 0.044
*P < 0.05 versus Time 0.
the rat may cause an increase in intraluminal water diffusion and mucosa! damage. 18· 19 However, these osmolalities may not be uncommon in ruminants; in adult sheep the osmolality of ruminal contents can increase threefold or more after meals of easily digestible carbohydrates.20 Thus the hypertonicity of the saline solution may be within the physiologic range of the adult rumen. Notably, the rumen of the ovine fetus at 128 days' gestation has been demonstrated to contain a keratinized epithelium, similar to that of the adult. 21 The intraruminal administration of 3% saline solution resulted in a significant increase in fetal plasma osmolality and sodium concentration. Although the actual site of fluid and electrolyte transfer within the gastrointestinal tract cannot be determined from this study, either gastrointestinal sodium was absorbed or plasma water was secreted into the gastrointestinal tract in response to luminal hypertonicity. The present results indicate an apparent preservation of plasma volume, as evidenced by the stable fetal hematocrit and the maintenance of glomerular filtration rate. Thus it is unlikely that significant plasma water entered the fetal gastrointestinal tract. However, active transport of sodium from rumen contents to blood has been demonstrated.21 Thus the data suggest that sodium absorption from the rumen or small intestine accounted for the increased plasma osmolality. Tows to less et al. 22 have demonstrated that placental water transfer is the major determinant of plasma osmolality in the ovine fetus; fetal kidneys compensate minimally for acute alterations in fetal water homeostasis. The present data indicate that ovine fetal gastrointestinal water and electrolyte transfer may be more rapid after ruminal infusion of hypertonic saline (-1000 mosm) than can be compensated by either fetal renal function or placental equilibration. The increase in fetal plasma osmolality was sufficient to stimulate fetal AVP secretion. In adult mammals AVP secretion generally occurs in response to a 2% increase from basal plasma osmolality. 23 In the present study a
significant increase in fetal plasma AVP occurred in response to only a 1% change in plasma osmolality. It is unlikely that plasma osmolality thresholds for AVP secretion are more sensitive in the fetus at 120 days' gestation than in the adult. 6 However, it is possible that resorption of hypertonic fluid in the gastrointestinal tract stimulated local hepatoportal osmoreceptors involved in AVP secretion. 24 Vasopressin stimulation resulted in the expected increase in urine osmolality and sodium and potassium concentrations and in decreases in urine volume and free water clearance. Consistent with AVP action, there was no significant alteration in glomerular filtration rate, with preservation of osmolar clearance. Thus, despite the significant gastrointestinal osmolar load, the urinary excretion of electrolytes was not increased in the fetus; placental transfer or perhaps the interstitial space likely accommodates the increased fetal body sodium. Amniotic fluid is hypotonic to fetal plasma in the basal state. However, increased amniotic fluid osmolality may occur during maternal dehydration 6 or periods of chronically elevated levels of fetal plasma AVP.' Previously we demonstrated that intraamniotic AVP may be recirculated to the fetus, presumably by swallowing; this results in increased plasma AVP levels and urinary hyperosmolality. 25 The current study suggests that fetal swallowing of hyperosmolar amniotic fluid may stimulate fetal AVP secretion, urinary hyperosmolality, and thus perhaps a further increase in amniotic fluid osmolality and AVP concentration. In summary, fetal bouts of swallowing of isotonic fluid may have little short-term impact on fetal plasma composition or urinary function. Slow absorption of gastrointestinal fluid or placental compensation for fluid resorption thus may serve to assure stable rates of fetal urine flow. The intraruminal administration of hypertonic fluid, however, has significant impact on fetal plasma osmolality, AVP secretion, and urine production. Although transplacental water and electrolyte
1412
Ross et al.
equilibration generally maintains fetal plasma homeostasis, the present data indicate that alterations in ovine fetal plasma composition as a result of gastrointestinal absorption may occur more rapidly than may be compensated by placental exchange. This observation suggests that fetal swallowing may influence amniotic fluid homeostasis by both absorption of fluid and subsequent regulation of production. We are grateful to Glenda Calvario for technical assistance and Sharon Schuler for manuscript preparation. REFERENCES 1. Abramovich DR, Garden A, Jandial L, et al. Fetal swallowing and voiding in relation to hydramnios. Obstet Gynaecol 1979;54: 15-20. 2. Gitlin D, Kumate J, Morales C, et al. The turnover of amniotic fluid protein in the human conceptus. AM J OBSTET GYNECOL 1972; 113:632-45. 3. Tomada S, Brace RA, Longo LD. Fate of labeled albumin and erythrocytes following injection into amniotic cavity of sheep. Amj Physiol 1986;251:R781-6. 4. Bradley RM, Mistretta CM. Swallowing in fetal sheep. Science 1973;179:1016-7. 5. Harding R, Bocking AD, Sigger JH, et al. Composition and volume of fluid swallowed by fetal sheep. Q J Exp Physiol 1984;69:487-95. 6. Bell RJ, Congiu M, Hardy KJ, et al. Gestation dependent aspects of the response of the ovine fetus to the osmotic stress induced by maternal water deprivation. Q J Exp Physiol 1984;69: 187-95. 7. Ross MG, Ervin MG, Leake RD, et al. Amniotic fluid ionic concentration in response to chronic fetal vasopressin infusion. Amj Physiol 1985;157:1292-7. 8. Smith FG, Lumbers ER, Kesby GJ. The renal response to the ingestion of fluid by the fetal sheep. J Dev Physiol I 986;8:259-66. 9. Robillard JR, Weitzman RE. Developmental aspects of the fetal renal response to exogenous arginine vasopressin. Am] Physiol 1980;238:F407-14. 10. Weitzman RE, Reviczky A, Oddie TH, et al. Effect of osmolality on arginine vasopressin and renin release after hemorrhage. Am J Physiol 1980;238:E62-8.
December 1988 Am J Obstet Gynecol
11. LaRochelle ET, Stem P, North WG. A new extraction of arginine vasopressin from blood: the use of octadecasilylsilica. Pflugers Arch Eur J Physiol 1980;387:79-81. 12. Kaiser MH. Water and mineral transport. In: JE Berk, ed. Bockus gastroenterology, Philadelphia: WB Saunders, 1985: 1538-52. 13. Levin RJ, Koldovsky 0, Hoskovaj, et al. Electrical activity across human foetal small intestine associated with absorption processes. Gut 1968;9:206-13. 14. Wright GH, Nixon DA. Absorption of amniotic fluid in the gut of the foetal sheep. Nature 1961; 190:816. 15. Warner ACI, Stacy BD. Water, sodium, and potassium movements across the rumen wall of sheep. QJ Exp Physiol 1972;57: 103-19. 16. Ross MG, Ervin MG, Lam RW, et al. Plasma atrial natriuretic peptide response to volume expansion in the ovine fetus. AMJ OBSTET GYNECOL 1987;157:1292-7. 17. Kvietys PR, Pittman R, Chou CC. Contribution of luminal concentration of nutrients and osmolality of postprandial intestinal hyperemia in dogs. Proc Soc Exp Biol Med 1976; 152:659-63. 18. Johnson L, Nordstrom H, Nylander G. Experimental studies on fluid pathophysiology in small intestinal obstruction in the rat. I. Effects of intraluminal hyperosmolality. Scand J Gastroenterol 1978; 13:49-56. 19. Teichberg S, Lifshitz F, Pergolizzi R, Wapnir RA. Response of rat intestine to a hyperosmotic feeding. Pediatr Res 1978; 12:720-5. 20. Engelhardt WV. Movement of water across the rumen epithelium. In: Phillipson AT, ed. Physiology of digestion and metabolism in the ruminant. Boston: Oriel Press, 1969: 132-46. 21. Steven DH, Marshall AB. Organization of the rumen epithelium. In: Phillipson AT, ed. Physiology of digestion and metabolism in the ruminant. Boston: Oriel Press, 1969:80-100. 22. Towstoless MK, Congiu M, Coghl~n JP, et al. Placental and renal control of plasma osmolality in chronically cannulated ovine fetus. Am J Physiol 1987;253:R389-95. 23. Berl T, Anderson RJ, McDonald KM, et al. Clinical disorders of water metabolism. Kidney Int 1976;10:117-32. 24. Baertschi AJ, Massy Y, Kwon S. Vasopressin responses to peripheral and central osmotic pulse stimulation. Peptides 1985;6:1131-5. 25. Ervin MG, Ross MG, Leake RD, et al. Fetal recirculation of amniotic fluid arginine vasopressin. Am J Physiol I 986;250:E253-8.