-Seven singleton 120-day fetal lambs were prepared with a shunt from the lung to the gastric end of the esophagus, a bladder catheter, and multiple amniotic fluid and vascular catheters. The urachus was ligated. Beginning 7 days later, amniotic fluid volumes were determined by drainage, followed by replacement with 1 liter of lactated Ringer (LR) solution. Urine flow into the amnion was measured continuously. In 14 of 27 experiments, amniotic fluid volumes were determined again 2 days after the inflow into the amnion had consisted of urine only and in 13 experiments after the inflow of urine had been supplemented by an intraamniotic infusion of LR solution. Intramembranous absorption was calculated from the inflows and the changes in volume between the beginning and end of each experiment. The relations between absorption rate and amniotic fluid volume, the "function curves," were highly individual. Urine production during the infusion of LR solution did not decrease, fetal plasma renin activity decreased (P Ͻ 0.001), and amniotic fluid volume increased by 140% [SE (27%), P Ͻ 0.005], but the increase in the amniochorionic absorption rate of 411% [SE (48%), P Ͻ 0.001] was greater (P Ͻ 0.005) than the increase in volume. Each of the seven fetuses was proven capable of an average intramembranous absorption rate that exceeded 4.5 liters of amniotic fluid per day. During the infusion of LR solution, the increase in the rate of absorption matched the rate of infusion (both in ml/h), with a regression coefficient of 0.75 (P Ͻ 0.001). Thus, even for large amniotic fluid volumes, volume is not limited by the absorptive capacity of the amniochorion, and, at least in these preparations, the position of the function curve and not the natural rate of inflow was the major determinant of resting amniotic fluid volume. fetus; polyhydramnios; amniochorion; intramembranous absorption DURING THE LAST 50 DAYS of the 150-day gestation period of fetal sheep, the production rate of amniotic fluid is on the order of 500 ml/day (6, 19). Under steady-state conditions, the rate of absorption will be the same. Because the volume of amniotic fluid is relatively constant over this period of time, it follows that this volume is almost perfectly controlled.Production of amniotic fluid results from fetal urination and lung fluid secretion (5, 13, 16). There is good evidence that urine production and lung fluid flow do not serve to regulate amniotic fluid volume because neither lung fluid flow nor urine production properly respond to induced changes in volume (9, 11). Thus, although substances secreted in these fluids may affect volume regulation (14), whatever regulatory mechanism exists must modulate the rate of fluid elimination to adapt to changes in fluid production. Fluid elimination consists of swallowing by the fetus and of absorption of fluid by the amniochorion, the membrane that surrounds the amniotic cavity. Amniochorionic absorption of amniotic fluid ["intramembranous absorption" (7, 14)] proceeds by means of an as-yetunresolved mec...

We investigated left ventricular (LV) hemodynamics, pressure-volume relations, and morphometry to determine what cardiac changes characterize pregnancy in the guinea pig. Time-bred virgin guinea pigs were paired by weight with unbred controls. Hemodynamic studies and LV pressure-volume relations were obtained on days 59-68 of the 68-day gestation. Weight of control sows increased from 817 to 902 g (P less than 0.01) and pregnant sows from 810 to 1,251 g (P less than 0.01). LV weights were not different. When indexed for maternal weight minus uterus and contents, pregnancy produced increases in O2 consumption, +48% (P less than 0.01); cardiac output, +32% (P less than 0.05); and stroke volume, +46% (P less than 0.025). Passive LV pressure-volume curves (dP/dV) were shifted to the right (P less than 0.025), but dP/dV at constant pressure was unchanged. Using a thin-walled spherical model, elastic modulus at constant stress was not different. The percent LV inter- and intracellular volumes and myocyte myofibril and organelle volumes were unchanged during pregnancy. In the guinea pig, pregnancy increases LV output, stroke volume, and size without changes in LV mass, morphometry, or elastic modulus.

The respiratory responses to theophylline during normoxia and hypoxia were determined in 13 unanesthetized fetal sheep. Theophylline (plasma levels-1 11 pmol/L) increased the incidence of fetal breathing movements measured over 120 min from 37.7 f 4.8% to 61.1 f

No abstract

ABSTRACT. The respiratory responses to theophylline during normoxia and hypoxia were determined in 13 unanesthetized fetal sheep. Theophylline (plasma levels -1 11 pmol/L) increased the incidence of fetal breathing movements measured over 120 min from 37.7 f 4.8% to 61.1 f 5.7% (SEM) in normoxic fetuses. In isocapnic hypoxia (arterial 0 2 tension -1.86 kPa), theophylline increased the incidence from 20.0 f 6.3 to 52.0 2 6.1%. Theophylline also resulted in an increase in the slope of inspiration during both normoxia and hypoxia. We conclude that adenosine modulates fetal respiratory drive during normoxia and hypoxia. In unanesthetized fetal sheep, acute hypoxia causes a depression in the incidence of fetal breathing movements (1, 2). This response is present in fetuses as early as 75-95 d gestation (3,4). Despite a number of investigations (5-9), a satisfactory explanation of the mechanisms involved in this response to hypoxia has not been forthcoming.In vagotomized, glomectomized adult animals, the depressive response to hypoxia can be attenuated by the adenosine receptor antagonist theophylline (10). In addition, a long acting analog of adenosine [Nh (L-2-phenylisopropyl) adenosine] causes respiratory depression in these preparations (1 I), and this effect can be reversed by theophylline (12). Similarly, in neonatal rabbits, phenylisopropyl adenosine results in depression of respiration, and this effect can be reversed with theophylline (13-15). Moss and Scarpelli (16) have shown that theophylline increases the fetal respiratory responses to COz. Some of the fetuses studied were acidemic and hypoxic, but these authors did not specifically determine if the adenosine antagonist would reverse the hypoxic depression of fetal breathing movements. Smith et al.( 1 7) produced prolonged fetal apnea by injecting i.v. phenylisopropyl adenosine into fetal sheep. Because the dose used resulted in a loss of low voltage electrocortical activity that is the permissive state for fetal respiratory activity (I 8), the specific effect on fetal breathing is difficult to evaluate.Our studies were performed to determine if the respiratory response to hypoxia could be altered by pretreating the fetus with theophylline. Because theophylline has been shown to stimulate fetal respiration during normoxia (16), this poses a difficulty in interpreting an effect during hypoxia. However, we reasoned that if adenosine contributes to the respiratory depression seen with MATERIALS AND METHODSThirteen pregnant ewes were used for these studies. Sterile surgery was camed out between 122 and 130 d gestational age under nitrous oxide and fluothane anesthesia in oxygen. The methods used for placement of catheters in the fetal trachea, axillary artery, sagittal vein, hind limb vein, and amniotic fluid and placement of electrodes above the dura have been described in detail (6). A polyvinyl catheter was inserted in the ewe's trachea and sutured to the S.C. tissues. This catheter was used for the addition of N2 and COz to the ewe's inspired air (20). ...