Volume and secretion rate of lung liquid in the final days of gestation and labour in the fetal sheep.

1. Most of the liquid that fills the lung of the fetal sheep in late gestation is cleared by the end of labour. Clearance of this liquid has a beneficial effect on postnatal gas exchange and therefore represents an important adaptation for postnatal life. Despite its importance, there is disagreement about whether clearance begins prior to labour, or occurs entirely within labour. 2. To address this issue, we made serial determinations of lung liquid volume by indicator dilution during late gestation and labour in the fetal sheep. 3. Regression analysis demonstrated that lung liquid volume exhibited a plateau level in the near-term fetus before it began to decline. Two models provided a fit to the decline in volume. In one, lung liquid clearance occurred in two linear phases, the first beginning 70 h before the study was terminated when the ewe was in advanced labour, the second occupying the last 8 h of the study period. In the initial phase, average lung liquid volume fell from 38.3 to 26.4 ml x kg(-1) before a rapid decline in the second phase reduced the volume to 13.8 ml x kg(-1). An exponential decay model was also found to fit the data; this showed a gradual decline in lung liquid volume in the 2 days preceding onset of labour, followed by a much more rapid decline within labour. 4. The rate of lung liquid secretion also declined in two linear phases, both of which commenced earlier than the changes in lung liquid volume. An exponential decay model also gave a significant fit to the data, but the fit was significantly weaker than that achieved with the two-slope model. 5. We conclude that clearance of lung liquid begins well before commencement of labour in the full term fetal sheep, and then accelerates once labour is established. In our study, lung liquid volume fell even in the absence of reabsorption of liquid across the pulmonary epithelium, indicating that outflow of liquid through the trachea must have occurred at a rate in excess of the secretion rate.

Influence of prenatal adrenaline infusion on arterial blood gases after caesarean delivery in the lamb.

The efficacy of pulmonary gas exchange immediately after delivery is inversely related to the volume of liquid in the lung at birth, but aspiration of as much liquid as possible from the lung before Caesarean delivery fails to improve postnatal oxygenation (Pa,O2) to the level achieved after spontaneous term delivery. We hypothesised that the differing respiratory benefit of aspiration and vaginal delivery results from the differing volume of lung liquid remaining after aspiration (17 ml (kg body weight)-1) and labour (7 ml kg-1). We addressed this hypothesis by reducing lung liquid volume to an estimated 7 ml kg-1 by infusing adrenaline to seven fetal lambs at 140 days gestation (term is 147 days) before performing Caesarean delivery and obtaining postnatal blood gases for comparison with samples from lambs delivered vaginally. Infusion of adrenaline to fetuses caused a progressive decline in arterial O2 saturation (Sa, O2), pH and base excess, but no change in arterial partial pressure of O2 (Pa,O2) or CO2 (Pa,CO2). After birth, Pa,O2 rapidly rose to the same level in adrenaline-treated and vaginal-delivery groups. A severe acidosis occurred in the adrenaline-treated group and this appeared to be related to a higher Pa,CO2 and a transiently lower Sa, O2 in this group. We conclude that adrenaline infusion can enhance postnatal Pa,O2 levels in the newborn lamb, but this beneficial effect may be outweighed by the severe acidosis that develops after prolonged prenatal adrenaline treatment.

Errors in estimating lung liquid volume in fetal lambs when using radiolabeled serum albumin and blue dextran.

Fetal lung liquid volume is usually determined by using radio-iodinated serum albumin (RISA) or blue dextran (BD) as volume tracers. We tested the reliability of both tracers at 124 (G124) and 142 days of gestation (G142; term = G147) when the labels were employed simultaneously. We measured the proportion of label bound reversibly to the lung, or apparently lost from the lung compartment, by washing out the lung with saline and 5% albumin. At G124, volume estimates with the two labels were similar. At G142, the volume estimate with BD (36.3 +/- 8.7 ml/kg of body wt) was higher (P < 0. 05) than with RISA (22.3 +/- 3.5 ml/kg). This difference resulted from reversible binding of BD, because 5% albumin washout released 38.5 +/- 4.0% of the BD added at the start of the experiment but a lesser amount of RISA (9.8 +/- 0.7%; P < 0.05). At G142, when RISA was used alone, its reversible binding was 1.3 +/- 0.2%. Background absorbance increased during experiments, giving rise to an apparent increase in BD concentration. We conclude that RISA is an effective tracer for lung liquid volume determination in the fetal lamb, whereas our findings of substantial epithelial binding of BD and large changes in background absorbance demonstrate that, under the conditions of our experiments, BD is a poor tracer close to term.

Massive decline in lung liquid before vaginal delivery at term in the fetal lamb.

OBJECTIVE: Our aim was to determine the volume of liquid remaining in the lungs of the fetal lamb just before a normal vaginal delivery at term to assess the extent to which an excess of liquid in the airspaces might contribute to the respiratory morbidity that accompanies elective cesarean delivery. STUDY DESIGN: The volume of liquid in the future airspace of the lungs was determined at the end of labor in eight fetal lambs at term from the dilution of an impermeable tracer (125I-labeled human serum albumin) mixed into the liquid. This volume was compared with that measured in a second group of 10 fetal lambs studied 7 days before the expected date of delivery (term = 147 days). RESULTS: The volume of lung liquid present at the end of labor was 6.8 +/- 1.0 ml x kg(-1) (n = 8) compared with 28.2 +/- 1.8 ml x kg(-1) (n = 10) in the second group of lambs studied before the onset of labor at 140 days of gestation. CONCLUSION: Our results indicate that the bulk (>75%) of the liquid that fills the lungs of the fetal lamb at 140 days of gestation is cleared at some time before normal term birth, suggesting that the adverse respiratory impact of elective cesarean delivery may be largely explained by denying the fetus this important adaptive mechanism.

Supraspinal influence on the development of motor behavior in the fetal lamb.

To examine the involvement of supraspinal inputs in the maturation of motor activity patterns in the developing fetal lamb, we recorded spontaneous electromyographic activity from spinally innervated muscles at approximately 45, 65, and 95 days gestation (G45, G65, and G95; term = 147 days). At G45, fetal activity occurred in synchronized activity-inactivity cycles of approximately 2 min duration, with the activity phase lasting 22.2 +/- 4.8 s and the inactivity phase lasting 95.4 +/- 13.3 s (mean +/- standard error of the mean, n = 5). At G65 and G95, the organization of activity was clearly different from that at G45 in that it was no longer cyclic, nor was the discharge of different muscles synchronized. By contrast, after spinal cord transection at G62, synchronised cyclic activity occurred in muscles innervated by segmental levels below the transection, both at G65 and G95. At G65 the duration of the activity phase of the cycle was 53.5 +/- 6.0 s, while the inactivity phase lasted 171.6 +/- 22.1 s; these durations did not alter between G65 and G95. Since spinal cord transection leads to the motor behavior of the G65 fetus reverting to the cyclic pattern characteristic of the G45 fetus, we conclude that supraspinal inputs begin to modulate the output of the spinal pattern generators at some stage between G45 and G65. The observation that spinally transected fetuses generate identical behavior at G65 and G95, both in terms of its cyclic character and the duration of cycles, suggests that spinal circuits undergo little autonomous development over this period; that is, the altered behavior observed in the developing intact fetus reflects the influence of supraspinal inputs on the motor circuits of the spinal cord.

Mechanism of action of triethyltin on identified leech neurons.

The effects of triethyltin (TET) have been examined using intracellular electrophysiological recording techniques from identified neurons of the leech (Hirudo medicinalis) CNS and from salivary glands of the giant Amazon leech (Haementeria ghilianii). TET, at concentrations as low as 10(-5) M, caused a reversible neuronal membrane depolarisation accompanied by an increase in firing frequency of action potentials (which could lead to conduction block at 10(-4) M) and a concomitant decrease in membrane resistance. TET-induced membrane depolarisation still occurred in saline where Na+, K+ and Ca2+ had been replaced by choline. TET decreased the rate of the depolarising and repolarising phases of the action potential. This also occurred in Haementeria salivary gland cells, in which the only inward cation channel is a calcium channel. The calcium channel blocker, manganese, did not block the effects of TET. TET counteracted the effects on the action potential of the potassium channel blocker, tetraethylammonium chloride (TEA). TET-induced neurotoxicity occurred independently of any resultant toxic effects on the myelin sheath. The action of TET is consistent with our view that it causes an increase of intracellular free Ca2+ probably via release from intracellular stores and inhibition of Ca2+ reuptake. A resulting inhibition of the Na+/K+ and Ca2+ pumps may also occur.

Effect of putative neuromodulators on rhythmic buccal motor output in Lymnaea stagnalis.

The effects of a variety of neuromodulator substances on rhythmic motor output and activity in neurons in the feeding circuitry of Lymnaea stagnalis were examined. Each neuromodulator produced a unique combination of effects at different levels in the network: i.e., pattern-generating interneurons (N1, N2, and N3), an identified higher-order interneuron (cerebral giant cell, CGC), and buccal motoneurons. 5-Hydroxytryptamine, acetylcholine, and FMRFamide all inhibited rhythmic motor activity. However, this was achieved in different ways. Dopamine changed the nature of rhythmic activity from one in which N2 interneuronal activity was predominant ("N2 rhythm") to a feeding rhythm. Dopamine was the only substance capable of activating the feeding rhythm. Activity in the CGC was increased by 5-hydroxytryptamine, dopamine, and acetylcholine and reduced by FMRFamide. Differential responses in buccal motoneurons were also observed. The results are discussed in relation to previous work on other species and also in terms of the selection of different patterns of motor output by neuromodulators.