Biomedical subjects

A M Perks

Publications and source records attributed to A M Perks.

At least 19 recordsLinked to original sources

PubMed1996

Effects of lung expansion on lung liquid production in vitro by lungs from fetal guinea-pigs. I. Basic studies and the effects of amiloride and propranolol.

Lungs from near-term fetal guinea-pigs were supported in vitro for 3 h; lung liquid production was measured by a dye-dilution method using Blue Dextran 2000 (fetuses 62 +/- 2 days of gestation, 97.6 +/- 19.0 (SD) g body weight; n = 134). Untreated control preparations produced fluid at 1.30 +/- 0.22 ml/kg body weight per h, and showed no significant changes during incubation (n = 30). After 1 h of incubation, experimental lungs were expanded with Krebs-Henseleit saline in volumes estimated to be below or approximating those of the first breath (n = 30; first breath, 0.6-1.2 ml). Expansions were graded at 18 +/- 4%, 31 +/- 4%, 43 +/- 3%, 50 +/- 3% and 72 +/- 2% of lung volume (volumes used for expansion at the maximal level, 0.64 +/- 0.25 ml). All expansions of 31% or above produced reductions in fluid production significant by analysis of variance (P < 0.01-0.001); production halted at 50% expansion, and there was strong reabsorption at 72% expansion (-0.87 +/- 0.45 ml/kg body weight per h by the final hour). There was an exponential relationship between percentage expansion and percentage fall in production (r = 1.00). There was no evidence for excessive pressure, and no evidence for lung damage as judged by electron microscopy or entry of intracellular materials into the fluid (lactic dehydrogenase, protein, K+). In studies based on 36 preparations, 10(-6) M amiloride present in the lung lumen (apically) abolished the reabsorptions seen at 70 +/- 3% expansion, but not the arrest of production; it had no effect on control preparations. Studies based on 24 preparations showed that responses to 72 +/- 2% expansion were not affected by 10(-7) M propranolol placed in the outer saline. In studies of 14 fetuses of widely different body weights (68.3-124.9 g), responses to 74 +/- 2% expansion showed an exponential increase with increasing body weight (r = 0.96). Although caution is needed, the results suggest that expansion of the lungs at birth may induce fluid reabsorption by an action independent of tissues outside the lungs, probably involving both activation of a Na(+)-based reabsorptive system and arrest of production, but not requiring beta-receptor activation. The probability that the responses are maximal at birth is discussed, and it is suggested that the effect of expansion may be a specialization of the perinatal lung.

Amiloride↗

PubMed1996

Effects of lung expansion on lung liquid production in vitro by lungs from fetal guinea-pigs. II. Evidence for generation of an inhibitory factor.

Lungs from near-term fetal guinea-pigs were supported in vitro for 3 h; lung liquid production was measured by a dye-dilution method using Blue Dextran 2000 [fetuses 63 +/- 2 days of gestation, 97.6 +/- 19.8 (SD) g body weight]. Preparations were incubated in pairs taken from the same mother. Twenty lungs incubated in pairs without treatment (controls) showed no significant changes in fluid production throughout incubation (analysis of variance; regression analysis); rates in successive hours were: first lung, 1.36 +/- 0.39, 1.09 +/- 0.34 and 1.27 +/- 0.42 ml/kg body weight per h; second lung, 1.46 +/- 0.52, 1.09 +/- 0.41 and 1.18 +/- 0.43 ml/kg body weight per h. Twenty lungs were incubated similarly in pairs, but after one hour one lung from each pair was expanded with Krebs-Henseleit saline in volumes approximating those of the first breath (68 +/- 10% of lung volume). The expanded lungs began to reabsorb fluid immediately after expansion; the untreated lungs also stopped production or reached reabsorption by the final hour. Rates in successive hours were: expanded lungs; before expansion, 1.00 +/- 0.21, after expansion, -0.23 +/- 0.17 and 0.14 +/- 0.09 ml/kg body weight per h; unexpanded lungs, 1.27 +/- 0.49, 0.02 +/- 0.01 and -0.01 +/- 0.004 ml/kg body weight per h. The decrease in production was significant for each type of lung. The effects persisted in both expanded and unexpanded lungs in the presence of 1.78 x 10(-5) M phentolamine (n = 12; 70 +/- 2% expansion). The results suggest that expansion of the lungs at birth may release an unknown inhibitory factor, provisionally termed Expansion Factor (EF), within the lungs; this agent, probably not a catecholamine, can change lung fluid production into reabsorption and may partly account for the failure of beta-antagonists to prevent fluid reabsorption at delivery.

Absorption↗

PubMed1996

Effects of acetylcholine on lung liquid production by in vitro lungs from fetal guinea pigs.

Lungs from near-term fetal guinea pigs (61 +/- 2 days of gestation) were supported in vitro for 3 h; lung liquid production was monitored by a dye dilution method. Untreated preparations produced lung liquid with no significant changes (ANOVA; regression analysis) (rates in successive hours, initial study: 1.37 +/- 0.30, 1.36 +/- 0.30, and 1.28 +/- 0.27 mL.kg-1 body weight.h-1; n = 6). Preparations given acetylcholine at 10(-4) (n = 6), 10(-5) (n = 6), and 10(-6) M (n = 18) during the middle hour showed marked and significant fluid reabsorption (p < 0.025-0.0005); 10(-8) M acetylcholine was without effect. Reductions were linearly related to log concentration of acetylcholine (r = 0.97; theoretical threshold, 1.0 x 10(-7) M acetylcholine). Atropine, at 10(-5) M, greatly reduced responses to acetylcholine, and all reabsorptions were abolished; 10(-4) M atropine completely abolished all responses to acetylcholine; atropine alone had no effect (based on 48 studies). The alpha-adrenoreceptor antagonist phentolamine (1.78 x 10(-5) M) abolished the effects of 10(-6) M acetylcholine, but had no effect alone (based on 48 studies); the beta-adrenoreceptor antagonist propranolol (10(-5) M) had no effect on responses to 10(-6) M acetylcholine (based on 24 studies). It is suggested that acetylcholine at physiological levels can produce lung liquid reabsorption by activating muscarinic receptors and releasing catecholamines within the lungs; these catecholamines act via alpha-receptors. This raises the possibility of neural controls of lung liquid reabsorption during the early stages of delivery or neonatal life.

Absorption↗

PubMed1994

Regulation of lung liquid secretion in immature fetal sheep: hormonal interaction.

The present studies were designed to test the hypothesis that arginine vasopressin (AVP) can interact with hydrocortisone and 3,5,3'-triiodothyronine (T3) to induce maturation of lung liquid reabsorptive processes in fetal sheep < 130 days gestation. Lung liquid production rates were measured in chronically catheterized thyroidectomized fetal sheep during eight different experimental treatments. Each experiment consisted of a 2-h control period followed by a 5-h treatment period. Net secretion or reabsorption of lung liquid was measured by using impermeant marker dilution techniques. AVP alone (50 mU/kg bolus plus 5.0 mU.kg-1.min-1 i.v. infusion) does not alter lung liquid secretion in fetal sheep 125 +/- 0.72 (SE) days gestation. In contrast, AVP (same dose as above) with T3 (30 micrograms) and hydrocortisone (6.94 mg/min) depressed lung liquid secretion and caused reabsorption of fluid. T3 alone, T3 and hydrocortisone, T3 and AVP, hydrocortisone alone, hydrocortisone and AVP, and saline did not result in net lung liquid reabsorption over a 5-h treatment period. These investigations demonstrate that AVP, T3, and hydrocortisone interact to cause lung liquid reabsorption in immature fetal lungs.

Absorption↗

PubMed1993

Reabsorption of lung liquid produced by 2,4-dinitrophenol in in vitro lungs from fetal guinea pigs.

Lungs from near-term fetal guinea pigs (62 +/- 2 days of gestation) were supported in vitro for 3 h, and lung liquid production was measured by a dye dilution technique. Twelve untreated preparations produced fluid at 1.54 +/- 0.29 mL.kg-1 body weight.h-1 during the 1st h, with no significant changes in later hours. Twelve preparations treated with 2 x 10(-4) M 2,4-dinitrophenol (DNP) showed strong reabsorptions (significant, ANOVA and regression analysis); total loss of lactate from the preparations doubled (significant, same tests). In 12 additional preparations, increasing DNP fivefold did not abolish reabsorption; results resembled those at the lower concentration. Amiloride at 10(-6) M abolished reabsorptions after 2 x 10(-4) M DNP, although fluid production still halted (n = 6; reductions significant, same tests). Amiloride alone had no effect (n = 6); untreated controls showed no change (n = 6). Similarly, 10(-4) M sodium iodoacetate virtually abolished reabsorptions after 2 x 10(-4) M DNP, although fluid production still stopped (n = 6; reductions significant, same tests). Iodoacetate alone only reduced fluid production (n = 6; significant, same tests); untreated controls showed no change (n = 6). The results suggest that reabsorptions seen after inhibition of oxidative processes depend on amiloride-sensitive Na+ channels and glycolytic metabolism.

2,4-Dinitrophenol↗

PubMed1993

Amiloride inhibits arginine vasopressin-induced decrease in fetal lung liquid secretion.

The effects of arginine vasopressin (AVP) and amiloride were studied in 16 unanesthetized fetal sheep (129-135 days of age) with indwelling catheters. Secretion was measured by an impermeant tracer technique. Control fetuses showed no change in lung liquid secretion over a 5-h period with an average secretion rate of 3.6 +/- 0.31 ml.kg-1.h-1. Infusion of AVP (23.4 +/- 2.23 mU.kg-1.min-1) in seven fetuses (134-140 days of age) produced significant decreases (from control) in the secretion rate over a 5-h period: the secretion rate decreased by 68% in the last hour. Amiloride placed in the lung liquid during infusion of AVP, but after AVP effects had taken place, reversed the AVP-induced decrease in lung liquid secretion. AVP in conjunction with other hormones that are elevated during the stress of birth (epinephrine and cortisol) may be important in the removal of lung fluid at birth.

Adenylyl Cyclases↗

PubMed1993

Fluid production by in vitro lungs from near-term fetal guinea pigs: effects of cortisol and aldosterone.

Lungs from near-term fetal guinea pigs (62 +/- 1 days of gestation) were supported in vitro for 3 h and fluid production was determined by a dye dilution method (Blue Dextran 2000). Three groups of control preparations (N = 6 for each group) showed no changes during incubation. However, cortisol or aldosterone placed in the outer saline during the middle hour caused profound reductions in fluid production. Cortisol at 10(-6) or 10(-8) mol/l reduced production 80.3 +/- 10.8% and 47.8 +/- 20.5%, respectively (p < 0.05-0.001; N = 6 for each group); at 10(-10) mol/l it failed to affect production significantly. Aldosterone was effective at lower concentrations (N = 12). At 10(-11) mol/l it reduced production 67.1 +/- 10.0% (p < 0.01-0.001); at 7 x 10(-10) mol/l it produced similar effects. In contrast, there were no significant changes after treatment with 10(-11) mol/l aldosterone together with an aldosterone antagonist (5 x 10(-8) mol/l spironolactone; N = 6). Spironolactone alone was without effect (N = 6). The highest steroid concentrations tested corresponded to plasma concentrations in the guinea pig at delivery; therefore, it is suggested that both steroids may have a role in reducing lung fluid production close to birth in this species.

Aldosterone↗

PubMed1993

Lung liquid production by in vitro lungs from fetal guinea pigs: effects of arginine vasopressin and arginine vasotocin.

Lungs from near-term fetal guinea pigs were supported in vitro for 3 h; lung liquid production rates were measured by a dye dilution technique. Seventy preparations were used to study the effects of arginine vasopressin (AVP) placed in the outer saline for the middle hour, at concentrations reported at birth [fetuses 61 +/- 2 days of gestation; 94.7 +/- 16.2 g (SD) body weight]. At 1200 microU/ml, AVP arrested fluid production (rates, successive hours, 3.03 +/- 0.60, 0.50 +/- 0.14 and 0.02 +/- 0.08 ml/kg body weight per h; falls significant, P < 0.01-0.0005). At 600, 300 and 100 microU/ml there were significant but smaller reductions. Reabsorptions were seen in 8 preparations given 600-1200 microU/ml, AVP. Preparations given 10 microU/ml AVP, AVP carrier or control saline showed no significant change. The responses (% reductions during treatment), were linearly related to the log concentration of AVP (r = 0.99); theoretical threshold, 8 microU/ml). Increasing treatment to 2h did not increase final responses. Preparations from 5 fetuses > 120 g body weight showed significantly greater responses (P < 0.025) [fetuses 64 +/- 2 days of gestation; 135.1 +/- 18.6 g (SD) body weight]. 10(-6) M amiloride abolished responses to AVP [fetuses 62 +/- 1 days of gestation; 93.4 +/- 18.5 g (SD) body weight, n = 30; rates, succeeding hours; AVP alone, 1.78 +/- 0.22, 0.48 +/- 0.09, 0.16 +/- 0.99 (P < 0.01-0.0005); AVP with amiloride, 1.15 +/- 0.07, 0.93 +/- 0.10, 0.86 +/- 0.08 (no significant fall) ml/kg body weight per h]. Thirty-six preparations treated with arginine vasotocin (AVT, 10-600 microU/ml) showed closely similar responses to those from AVP. These studies extend results to fetal guinea pigs, and show that AVP, at concentrations reported at delivery, can slow lung liquid production or cause reabsorption by a direct action on the lung. The effect increases close to term, and is due to activation of amiloride-sensitive Na+ channels.

Amiloride↗

PubMed1992

Effects of cAMP, its analogues, and forskolin on lung fluid production by in vitro lung preparations from fetal guinea pigs.

Lungs from fetal guinea pigs (62 +/- 1 days of gestation) were supported in vitro for 3 h and fluid production was determined by a dye dilution method, based on Blue Dextran 2000. Twenty untreated lungs produced fluid at 1.41 +/- 0.22 mL.kg-1 body weight.h-1, with no significant changes during later hours. Treatments with analogues of cAMP, cAMP, or forskolin during the middle hour reduced production significantly. Dibutyryl cAMP at 10(-3) M produced reabsorption (117.8 +/- 13.6% reduction, p less than 0.001, n = 10); at 10(-4) M it reduced production (77.3 +/- 11.0% fall, p less than 0.001, n = 10). 8-Bromo-cAMP appeared more effective; at 10(-4) M it caused slight reabsorption (109.0 +/- 8.9% reduction, p less than 0.001, n = 6) and at lower concentrations it decreased production (at 10(-6) M, 67.6 +/- 9.6% fall, p less than 0.001, n = 6; at 10(-7) M, 40.0 +/- 14.3% fall, p less than 0.001, n = 6). At high doses, cAMP itself produced similar effects (at 5 x 10(-3) M, 141.6 +/- 22.8% reduction, p less than 0.001, n = 6); at 10(-4) it was ineffective (n = 3). Forskolin at 10(-6) M induced the strongest reabsorptions seen (159.1 +/- 10.9% reduction, p less than 0.001, n = 6); at lower concentrations it reduced production (at 10(-8) M, 73.8 +/- 5.5% fall, p less than 0.001, n = 6; at 10(-9) M, 29.2 +/- 9.2% fall, p less than 0.05, n = 6).(ABSTRACT TRUNCATED AT 250 WORDS)

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed1992

Effects of intravenous saline infusion on fetal ovine lung liquid secretion.

These studies were designed to investigate the relationship between body fluid volume expansion and secretion of lung liquid in fetal sheep. Twelve fetal animals were used for saline infusion studies after providing them with indwelling vascular catheters and an exteriorized tracheal loop. An additional 10 animals were used as controls. Lung liquid production was measured using an impermeant tracer technique (Blue Dye Dextran). Saline infusion at 1.6, 4.0, 15.6, and 19.2 ml.kg-1.h-1 did not alter significantly lung liquid secretion rates. These results demonstrate that 1) intravenous infusion of saline at relatively high rates in the ovine fetus does not affect net fetal lung liquid formation rate, and 2) the lungs of chronically catheterized, unanesthetized fetal sheep probably do not participate in regulation of excess fluid and electrolytes.

Animals↗

PubMed1992

Changes in somatostatin-like immunoreactivity in lungs from perinatal guinea pigs and the effects of somatostatin-14 on lung liquid production.

Somatostatin-like immunoreactivity was measured by radioimmunoassay with a monoclonal antibody in lungs from perinatal guinea pigs (62 +/- 2 days of gestation). Fetuses delivered by Caesarean section and dissected before breathing showed 4748 +/- 758 pg/lung (n = 25). Fetuses allowed to breathe (neonates) showed marked increases in activity: 7629 +/- 1355 pg/lung (n = 12) after breathing 30 seconds, and 10729 +/- 1064 pg/lung (n = 6) after breathing 3 minutes (2.3-fold increase, P < 0.005). Values then declined (5203 +/- 1050 pg/lung (n = 9) at 30 minutes; 1458 +/- 105 pg/lung (n = 4) at 60 minutes). Changes were similar in pg/g wet tissue. HPLC characterized the immunoreactive peptides as somatostatin-14 (SS-14) and somatostatin-28 (SS-28) in both fetuses and neonates (n = 11). SS-28 made up only 13.7 +/- 1.7% of the activity; this percentage did not change with breathing. The effects of synthetic SS-14 on lung liquid production were investigated in in vitro lungs from 42 fetal guinea pigs. All 21 preparations immersed in 10(-5)-10(-7) M SS-14 during the middle hour of 3 h incubations reduced production, often approaching zero after treatment (rates, ml/kg body weight per h, succeeding hours: 10(-5) M (n = 9), 3.09 +/- 0.68, 0.93 +/- 0.39, -0.05 +/- 0.60 (fall significant during and after treatment, P < 0.025-0.005); 10(-6) M (n = 6), 3.06 +/- 0.68, 1.29 +/- 0.58, 0.36 +/- 0.38 (P < 0.05-0.005); 10(-7) M (n = 6), 1.96 +/- 0.66, 1.11 +/- 0.34, 0.64 +/- 0.28 (P < 0.05-0.025).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Lung liquid production by in vitro lungs from fetal guinea pigs: studies with metabolic inhibitors.

Lungs from fetal guinea pigs (62 +/- 2 days of gestation) were supported in vitro for 3 h, and lung liquid production was measured by dye dilution. Eighteen untreated preparations produced fluid at 1.76 +/- 0.30 mL.kg-1 body weight.h-1 during the first hour, with no significant changes in later hours. When inhibitors of respiratory processes were placed in the outer saline during the middle hour, production changed significantly, as follows: (a) sodium iodoacetate at 10(-3) M stopped production (87.2 +/- 10.3 and 100% reductions, successive hours; n = 6), at 10(-4) M it reduced production (60.0 +/- 10.3 and 63.4 +/- 9.3% reduction, successive hours; n = 12); (b) sodium fluoride, 10(-3) M, almost stopped production (93.2 +/- 12.1 and 89.5 +/- 9.3% reductions, successive hours; n = 6); (c) sodium cyanide at high concentration (10(-3) M) reduced production slowly (35.5 +/- 12.3 and 73.1 +/- 22.4%; successive hours; n = 6); (d) sodium azide, 10(-3) M, also reduced production (67.6 +/- 14.2 and 59.7 +/- 14.0%, successive hours; n = 6); total lactate lost rose 1.8 +/- 0.5 fold; (e) dinitrophenol produced strong reabsorptions; at 10(-3) M, production fell 115.4 +/- 15.9 and 113.1 +/- 47.3%, successive hours (n = 4), and at 2 x 10(-4) M it fell 143.8 +/- 33.8 and 153.4 +/- 26.7%, successive hours (n = 6); total lactate lost rose 2- to 3-fold. Control preparations showed no significant changes. The results suggest that lung liquid production requires glycolysis and aerobic metabolism. However, reabsorption appears to continue on glycolysis alone, a particularly useful situation for neonates suffering respiratory distress.

Animals↗

PubMed1990

Fluid production by in vitro lungs from fetal guinea pigs.

Lungs from fetal guinea pigs (54-67 days of gestation) were supported in vitro, and lung liquid secretion rates were measured by a dye-dilution technique. The average secretion rate in the first hour was 2.14 +/- 0.08 (SE) mL x kg-1 body weight.h-1 (0.21 +/- 0.01 mL/h) (n = 450); this was comparable to intact preparations. In an independent study of 30 lungs, secretion continued unchanged for 3 h, with no significant change in fluid composition. Between 54 days and term, production appeared to fall in terms of millilitres per kilogram per hour. The following agents were placed in the supporting saline during the middle hour of incubation. (i) Sodium iodoacetate: at 10(-4) M this produced a fall in secretion (fall, succeeding hours; 55.4 +/- 23.0 and 64.9 +/- 17.5%; n = 6); at 10(-3) M it stopped secretion (fall, succeeding hours; 87.2 +/- 10.3 and 100%, n = 6). (ii) Ouabain: at 10(-5) M there was no change in production (n = 6); at 10(-4) M, four preparations were unaffected, two reduced production. (iii) Epinephrine (10(-7) M) produced a significant fall in production in all cases (n = 6); in four preparations secretion reduced (average fall, 64.4 +/- 10.8%); in two preparations there was reabsorption (average rate, -1.03 mL.kg-1.h-1). This extends the effect of epinephrine to the guinea pig, and suggests that the in vitro preparation is a useful model for studies of the fetal lung.

Animals↗

PubMed1990

The effects of furosemide and bumetanide on lung liquid production by in vitro lungs from fetal guinea pigs.

Lungs from fetal guinea pigs of 61 +/- 3 days of gestation were supported in vitro for 3 h, and lung liquid secretion rates were measured by a dye dilution technique based on Blue Dextran 2000. Ten preparations that had received no treatment showed an average secretion rate of 1.12 +/- 0.28 mL.kg-1 body weight.h-1 during the first hour, and there were no significant changes over the following 2 h. In studies of 54 fetal lungs, furosemide, bumetanide, control ethanol carrier, or saline alone were placed in the supporting medium during the middle hour of the 3-h incubations (ABA design). Furosemide at 10(-3) M reduced secretion 83.4 +/- 16.8%; at 10(-4) and 10(-5) M it produced smaller reductions. Bumetanide at 10(-3) M usually produced reabsorption (129.9 +/- 23.0% reduction), at 10(-4) M it reduced secretion 30.9 +/- 11.8%, but at 10(-5) M it was ineffective. Control carrier and saline were without effect. The ability of the loop diuretics to produce reabsorption of fluid in some preparations suggests the unmasking of an active reabsorptive process. The results also suggest that lung liquid secretion in the fetal guinea pig, as in the sheep, is dependent on a Na+ and Cl- cotransport system.

Animals↗

PubMed1990

The effects of temperature change on lung liquid production by in vitro lungs from fetal guinea pigs.

Lungs from fetal guinea pigs of 58-65 days of gestation were supported in vitro for 3 h, and lung liquid production rates were measured by a dye dilution technique. In 36 control preparations, incubated continuously at 37 degrees C, the average production rate in the first hour was 1.46 +/- 0.23 ml/h per kg body weight; there was no significant change over the following two h. In 36 further preparations the temperature was changed during the middle hour (ABA), with the following % reductions in production rates: at -1 degrees C (relative to 37 degrees C), 68.2 +/- 17.1%; -2 degrees C, 125.5 +/- 30.1% (reabsorption); -3 degrees C, 103.8 +/- 32.8% (reabsorption); -5 degrees C, 82.7 +/- 16.6%, -8 degrees C, 94.7 +/- 1.8 %; +2 degrees C, 100.7 +/- 12.6% (all significant, P less than 0.025-0.005). Slow recoveries followed a return to starting conditions, except after the increase in temperature, 10(-6) M amiloride abolished reabsorption, but not depression, during the maximal effects of temperature reduction (at -2 degrees C, n = 6); amiloride had no effect on control preparations (n = 6). These results suggest that: (a) reductions of 2-3 degrees C, as seen in the delivery room, abolish secretion, but not reabsorption of lung fluid; larger reductions stop both processes; (b) the reabsorptions seen after a fall in temperature depend on Na(+)-transport mechanisms; (c) lung liquid production was sensitive to a rise in temperature, so that fevers might adversely affect lung development, and (d) the fall in temperature at birth may be an important factor in the early reabsorption of lung liquid.

Absorption↗

PubMed1989

The effects of arginine vasopressin and epinephrine on lung liquid production in fetal goats.

The effects of arginine vasopressin (AVP) and epinephrine on lung liquid secretion were investigated in 67 acute fetal goats (116 days of gestation to term) with intact umbilical cords after caesarean section. Secretion was measured by an impermeant tracer technique. AVP was infused intravenously (1.6-39.2 mU/(kg.min); 2 h) into 26 fetuses. All fetuses below 130 days of gestation, except one, showed no response. All above 133 days reduced secretion, or turned to reabsorption, except at the lowest infusion rate. The effect persisted, and usually increased postinfusion. Expansion of the lungs with saline did not change the response. The percentage reductions were linearly related to the logarithm of the infusion rate (threshold, 1.42 mU/(kg.min]. The absolute reductions were linearly related to fetal weight. Epinephrine was infused intravenously (0.30-6.72 micrograms/(kg.min); 1-2 h) into 12 fetuses. All fetuses (118 days to term) reduced secretion or reabsorbed by the second hour. At the highest infusion rate, reabsorption was immediate; at the lowest, secretion increased slightly, then fell significantly in the second hour. Epinephrine acted at levels considered physiological at delivery in the sheep. AVP appears to act at plasma levels found in most vaginal deliveries; it may augment epinephrine-induced reabsorption during stress, and help long-term removal of lung fluid.

Animals↗

PubMed1986

The effects of bumetanide and furosemide on lung liquid secretion in fetal sheep.

Thirty-four experiments were carried out on the effects of loop diuretics on lung liquid secretion in 20 fetal sheep (128-145 days gestation) with indwelling catheters. Bumetanide placed in the lung liquid at 2.19 +/- 0.52 X 10(-4) M produced immediate reabsorption of fluid, and effects lasted 3 hr (n = 6). Bumetanide at 1.1 +/- 0.17 X 10(-5) M reduced secretion significantly for 2 hr (n = 4), but at 1.07 +/- 0.06 X 10(-6) M there was no clear effect (n = 6). Controls showed no significant change (n = 6). Furosemide was less effective. At 3.1 +/- 0.07 X 10(-3) M it produced an immediate reabsorption, which lasted 3 hr, but at 1.0 +/- 0.04 X 10(-4) M it increased secretion slightly (n = 4); controls showed no significant change (n = 6). The results are consistent with the presence of a chloride transport system, perhaps with sodium cotransport, as the major factor in fetal lung liquid secretion.

Animals↗

PubMed1985

The rate of production of lung liquid in fetal goats, and the effect of expansion of the lungs.

Fetal goats (95-155 days of gestation), delivered by Caesarian section, under chloralose (50 mg/kg), with intact umbilical cords, were monitored for lung fluid production by an impermeant tracer method. The average rate of production was 13.4 +/- 2.3 ml/h, or 6.0 +/- 0.9 ml/h per kg. Production rose exponentially towards birth, by both parameters, significant P less than 0.0001 (ml/h), or P less than 0.0005 (ml/h per kg). This indicated an increase in lung liquid production due to both growth and increased activity of the tissues. However, considerable individual variability, even between twins, suggested that this general pattern was modulated by physiological requirements. In 14 fetuses (plus 12 controls), expansion of the lungs with volumes of saline similar to those of the first inspirations (saline, 15-40 ml, matched to the optical density of the lung fluid; inspiration by spirometer, 20-25 ml), caused reduction of secretion or reabsorption of fluid. Secretion changed to reabsorption at about 50% expansion, and the probable physiological limit was estimated at 62-68% expansion. The logarithm of the % fall in production was linearly related to the % expansion (r = 0.88; P less than 0.0001); therefore, small expansions (equivalent to intrauterine breathing) would have little effect, but larger changes such as first breaths, would produce rapidly escalating effects. Controls showed no similar activity. Changes in Na+ and Cl- ions are in parallel to those of water. However, K+ ions moved into the lungs after expansion, in the opposite direction to Na+ ions, and against their concentration gradient. It is suggested that expansion of the lungs activates a Na+/K+ ATP-ase pump to aid reabsorption of salt and water at birth.

Animals↗