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L B Strang

Publications and source records attributed to L B Strang.

At least 19 recordsLinked to original sources
PubMed1991

Development of the lung liquid reabsorptive mechanism in fetal sheep: synergism of triiodothyronine and hydrocortisone.

1. Thyroidectomy was performed on twelve fetal sheep between 111 and 115 days gestation. Measurement of fetal lung liquid secretion and absorption rates (Jv) were made at rest and during short (45 min) and long (5 h) infusions of adrenaline (0.5 micrograms/min) in a total of thirty-seven experiments, some in the absence of triiodothyronine (T3) and hydrocortisone and some at set times after the administration of the two hormones. 2. T3 was given either as an I.V. infusion (60 micrograms/24 h) or as a bolus of 30 micrograms; hydrocortisone was given as an infusion of 10 mg/24 h. Both hormones were administered together. 3. Before T3 and hydrocortisone were given short infusions of adrenaline had no effect on Jv but 4 h after exposure to the hormones secretion rate was reduced to near zero (Jv = -0.5 +/- 1.6 ml/h, n = 4) by adrenaline; after 24 h of hormone exposure, absorption of fetal lung liquid was produced by adrenaline (Jv = -3.6 +/- 2.2 ml/h, n = 4) which was even greater after 72 h, (Jv = -11.2 +/- 2.2 ml/h, n = 4). 4. During long infusions of adrenaline when T3 and hydrocortisone were given at the start of the experiment, an effect on lung liquid secretion was evident at 2 h and absorption was produced at 4 h (Jv = -4.2 +/- 2.5 ml/h, n = 3). The effect was significantly different from control long infusions of adrenaline performed the previous day in the absence of hormones. 5. After 24 or 48 h of stopping T3 and hydrocortisone administration, adrenaline no longer produced absorption of lung liquid, indicating that the effect of the two hormones was reversible within 24-48 h. 6. The protein synthesis inhibitor cycloheximide put into lung liquid (4 x 10(-5) to 3 x 10(-4) M) blunted the effect of the hormones at 4 h and prevented absorption of lung liquid at 24 h. Jv during adrenaline was -3.6 +/- 1.5 ml/h in control experiments but was +3.3 +/- 0.9 ml/h after cycloheximide, n = 4, P < 0.01. This indicated that the two hormones produced their effect through protein synthesis.

Absorption↗
PubMed1990

The role of thyroid hormones in maturation of the adrenaline-sensitive lung liquid reabsorptive mechanism in fetal sheep.

1. Following thyroidectomy at 106-118 days fetal sheep were infused continuously with triiodothyronine (T3) from 110, 118, 125 or 131 days (n = 12) or with thyroxine (T4) from 118 days (n = 4) until the fetuses were delivered. Lung liquid secretion or absorption rates, heart rate, blood pressure and arterial blood gases were measured before and during 45 min periods of fetal infusions of adrenaline (n = 60) at 3-8 day intervals. The effects of T3 or T4 replacement on the response to adrenaline were compared with data previously obtained in groups of euthyroid (control) and thyroidectomized (Tx) fetuses. 2. Fetuses infused with T4 (50 micrograms/day) following thyroidectomy had plasma T4 and T3 concentrations in the normal fetal range. Fetal plasma T3 levels in fetuses infused with T3 (60 micrograms/day) were at or above the high end of the normal range for full-term fetuses. Those receiving 120 micrograms of T3 per day had levels equivalent to those normally seen in the postnatal T3 surge. 3. Normal maturation in the lung of the reabsorptive response of fetal lung liquid to adrenaline was seen in the fetuses infused with T3 or T4 from 118 days. A marginal advance in maturation was seen in fetuses infused with T3 from 110 days and a delay in maturation in those infused with T3 from 125 and 131 days.

Absorption↗
PubMed1990

Synergistic action of triiodothyronine and hydrocortisone on epinephrine-induced reabsorption of fetal lung liquid.

The influence of triiodothyronine and hydrocortisone on maturation of the response to epinephrine that leads to reabsorption of lung liquid was investigated in nine chronically catheterized fetal sheep. Experiments were performed on thyroidectomized fetal sheep at 116-120 d gestation, well before the reabsorptive response to epinephrine is normally seen. After i.v. administration of either triiodothyronine (60 micrograms/d) or hydrocortisone (10 mg/d) for 3 d (three fetuses in each case), all fetuses continued to secrete lung liquid during exposure to epinephrine (secretion rate = 5.9 +/- 3.2 mL/h in triiodothyronine-treated and 4.4 +/- 1.9 mL/h in hydrocortisone-treated fetuses). However, when the two hormones were administered together in the same doses to three fetuses, a striking reabsorptive response to epinephrine was seen (absorption rate = -12.3 +/- 3.6 mL/h), similar to that observed in the mature fetus. Induction of this capacity to reabsorb lung liquid may be of importance in the management of respiratory problems of the newborn infant.

Absorption↗
PubMed1989

Pulmonary glucose transport in the fetal sheep.

1. In the chronically catheterized sheep fetus between 122 and 143 days gestation the concentration of D-glucose in lung liquid was very low (usually less than 0.01 mM, the lower limit of detection of the analytical method) whereas the mean plasma concentration was 0.19 mM (S.E.M. 0.4, n = 13). 2. When the lung liquid concentration of D-glucose was raised to 1.67-5.00 mM, rapid uptake was observed until the concentration had fallen to its preceding low level. The uptake showed saturation kinetics (Vmax = 2.29-8.78 mumol/min, increasing with gestation; mean Km = 0.14 +/- 0.02 mM, n = 11, no change with gestation). This active uptake of glucose was blocked by phloridzin (10(-4) M). It was associated with a decrease in lung liquid secretion rate from which a change in net sodium flux could be inferred of an order suggesting one-to-one glucose-sodium co-transport. 3. Radiolabelled 3-O-methyl-D-glucose (3-O-meG) - a monosaccharide which is transported but not metabolized - was taken up rapidly from lung liquid and this rapid uptake was inhibited by D-glucose with 50% inhibition at 0.35 mM (+/- 0.08, n = 9). It was also inhibited by phloridzin (10(-4) M). 4. Radiolabelled 2-deoxy-D-glucose - a monosaccharide which is not a substrate for sodium-coupled transport - was taken up only very slowly from lung liquid; the rate of uptake was appropriate for passive diffusional transport and it was unaffected by the addition of D-glucose or phloridzin to lung liquid. 5. Intravenous infusion of D-glucose caused no detectable increase in the concentration of glucose in lung liquid unless phloridzin was added, when a slow increase was observed. 6. In two experiments with active transport blocked by phloridzin in lung liquid (10(-4) M), the rate of entry of labelled 3-O-meG from plasma to lung liquid was measured during intravenous infusion of this tracer for 29 and 23 h. The rates of entry were similar to the rate of efflux of the tracer from lung liquid when uptake was blocked by phloridzin or D-glucose, and similar to the rate expected for a metabolically inert tracer (i.e. it was some two orders of magnitude less than efflux from lung liquid in the absence of an inhibitor).(ABSTRACT TRUNCATED AT 400 WORDS)

3-O-Methylglucose↗
PubMed1989

Solute and water transport across the pulmonary epithelium: a new chapter in lung physiology inaugurated by Alfred Jost.

Early experiments by Jost and Policard demonstrated the presence of secretory activity in the lungs of the fetal rabbit. Subsequent work has demonstrated a system of active ion transport across the pulmonary epithelium of the sheep fetus, in which uphill movement of chloride ions to the pulmonary lumen provides the main force for lung liquid secretion. In the last 10-20% of gestation a reabsorptive mechanism in response to beta-adrenergic stimulation is developed which is brought into play in the perinatal period, clearing the lungs of liquid. The development of this response has been shown to require thyroid hormones. The action of adrenaline (or of a directly induced rise in intracellular cAMP) depends on the initiation of active sodium transport from the luminal side of the epithelium. Active glucose-sodium cotransport, maintaining a low glucose concentration in fetal pulmonary liquid, has also been demonstrated in this epithelium. In the postnatal period, sodium absorption continues to be a feature of the lung periphery and the epithelium of the conducting airways is known to be a site of an active ion transport system which features both chloride secretion and sodium absorption. However, this epithelium responds quite differently from the fetal peripheral epithelium to beta-adrenergic stimulation by increasing chloride secretion with little or no change in sodium absorption.

Animals↗
PubMed1988

The effect of thyroidectomy in the fetal sheep on lung liquid reabsorption induced by adrenaline or cyclic AMP.

1. In fetal sheep at 113-120 days' gestation, thyroidectomy was performed and tracheal, arterial and venous catheters inserted. Following a recovery period experiments were performed from 120-145 days to measure changes in lung liquid secretion or its absorption in response to I.V. adrenaline infusion or to introduction of dibuteryl cyclic AMP into lung liquid. The results were compared with those previously obtained in non-thyroidectomized fetuses. 2. Plasma levels of thyroid hormones in non-thyroidectomized fetuses confirmed the pattern found by previous workers. In thyroidectomized fetuses the levels of thyroxine (T4), tri-iodothyronine (T3) and reverse T3 (rT3) were very low except in one fetus which showed biochemical evidence of thyroid regeneration towards the end of gestation. 3. In thyroidectomized fetuses the normal response to adrenaline infusion (diminution of reversal of lung liquid secretion) was profoundly suppressed and very little gestational maturation in this response took place, except in the one fetus with evidence of thyroid regeneration in which a normal reabsorptive response developed in late gestation. 4. In thyroidectomized fetuses, the normal response to dibuteryl cyclic AMP was greatly reduced and its increase with gestation which normally parallels that seen during adrenaline infusion did not take place.

Absorption↗
PubMed1986

The role of amiloride-blockable sodium transport in adrenaline-induced lung liquid reabsorption in the fetal lamb.

Adrenaline was infused intravenously at rates of 0.1-1.0 microgram/min into chronically catheterized fetal lambs (125-141 days gestation) to induce slowing of secretion or reabsorption of lung liquid. There was an electrical potential difference (p.d.) of -0.3 to -9.5 mV (mean -3.4 mV) between lung liquid and plasma (lung liquid negative) during control lung liquid secretion. In response to adrenaline infusion, the p.d. increased (lung lumen more negative) and this change was greatest (1.8 +/- 0.3 mV) in experiments in which reabsorption occurred. Measurements were made of bidirectional fluxes of Na+ and Cl- across the pulmonary epithelium during control lung liquid secretion and during adrenaline infusion. Adrenaline-induced reabsorption of lung liquid was associated with an increase in Na+ flux from lung lumen to plasma. Similar but smaller changes occurred when the adrenaline response was slowing of secretion. The difference between measured flux ratios and those predicted from the forces determining passive flux provided evidence for active transport of Cl- from plasma to lung lumen, as previously demonstrated by Olver & Strang (1974). When adrenaline was infused, there was evidence of active Na+ transport in the direction lung lumen to plasma and an associated decrease in active Cl- transport in the opposite direction. These changes were greatest when the response to adrenaline was reabsorption. Amiloride, when mixed into the lung liquid to give a calculated concentration of 10(-4) M, abolished the changes in p.d. and ion flux induced by adrenaline. In experiments using amiloride concentrations between 10(-8) and 10(-4) M it was shown that 50% inhibition of the reabsorptive response to adrenaline (KI) was induced by 4 X 10(-6) M-amiloride in the lung lumen. Thus adrenaline-induced slowing of secretion or reabsorption of lung liquid is mediated by active Na+ transport from lung lumen to plasma and depends on amiloride-inhibitable Na+ channels on the luminal surface of the pulmonary epithelium.

Absorption↗
PubMed1976

The permeability of lung capillary and alveolar walls as determinants of liquid movements in the lung.

The lungs of the exteriorized fetal lamb offer an unusually good opportunity for measuring the permeability of lung capillary and alveolar walls, because access to plasma, interstitial fluid and alveolar liquid can be obtained without seriously disturbing their physiological relationships. Although there are probably some differences in permeability between fetal and air-breathing lungs, the underlying pattern appears to be similar. Large water-soluble molecules, including proteins, can penetrate capillary but not alveolar walls. The latter appear to be impermeable to molecules with diffusion radii greater than 0.5-0.6 nm. Pore theory can be used to characterize these permeabilities and to obtain estimates of osmotic reflection coefficients for various water-soluble substances. From them, predictions can be made of the bulk movements of liquid to be expected in a variety of circumstances, including the adaptation of the lungs at birth, lung oedema and drowning in sea water or fresh water.

Animals↗
PubMed1975

Changes in non-electrolyte permeability of alveoli and the absorption of lung liquid at the start of breathing in the lamb.

1. Experiments were done on mature foetal lambs, 135-145 days in gestation, exteriorized at Caesarean section, and on new-born lambs aged 12-60 hr. In the foetal lambs, test substances were added to lung liquid and then spontaneous ventilation was induced or the lungs were statically inflated with gas or saline. In the new-born lambs, the left lung was ventilated in order to maintain respiratory gas-exchange, while foetal lung liquid, taken from previous experiments and containing test substances, was introduced into the right lung, which was then inflated with gas and used for permeability measurements. In both foetuses and new-borns, the gas used was O2 or N2O and, at 20 min intervals, ventilation or static inflation was interrupted, the gas in the lungs absorbed into the circulation and the remaining liquid sampled through the trachea. The following test substances were used in various combinations: [14C]-erythritol, [3H]sucrose, [14C]inulin, [131I]albumin, and the polymer [131I]-PVP. The last of these was separated, after the experiments, by gel filtration with Sephadex G200 or G50, into fractions of defined molecular radius. [131I]albumin, or a large molecule fraction of [131I]PVP, was used as a volume marker. 2. Spontaneous ventilation was associated with the absorption of liquid and with an alteration in the foetal pattern of non-electrolyte permeability that could be characterized by postulating an opening up of water-filled cylindrical pores to 34-56 A in radium. In the new-born lambs, the results suggested pores 7-14 A in radius. 3. Static inflation of the foetal lungs with gas, to pressures of 25-35 cmH2O, gave permeabilities appropriate for pores 5-5-12 A in radius. Static inflation with gas, to pressures of 41-49 cmH2O, produced changes appropriate for much larger channels, more than 125 A in radius and possibly much larger. With one exception, expansion with saline produced changes similar to those obtained by gas inflation to 25-35 cmH20. 4. It was concluded that in the initial stages of pulmonary ventilation a change takes place in alveolar epithelial cells. The increase in size would be sufficient to allow for rapid liquid absorption, but is not so great as to permit significant penetration by plasma albumin. The results obtained in the lung of the new-born lamb statically inflated to 25-32 cmH2O suggest that, following the initial adaptation, alveolar permeability returns towards the foetal pattern, although the pores remain larger than in the foetus. The change in permeability pattern at birth appears to depend on the degree of lung expansion with gas.

Absorption↗
PubMed1975

[Important physiological considerations in artificial respiration and reanimation of newborn infants].

The methods used for ventilation of the neonate shold be based upon consideration of the physiological changes which occure in the lungs and circulation at birth of the normal infant. Three important changes must be taken into consideration. The first is the formation of a residual volume of alveolar gas, the second the resorption of pulmonary fluid and the third a decrease in pulmonary vascular resistance, upon which is dependent the change from foetal circulation to that of the neonate. To begin insufflation of foetal lungs it is necessary to use a pressure of between 20 and 30 cm H2O. After the first insufflation, a good deal of air remains in the lungs, even during expiration, as long as pulmonary "surfactant" is present. In the absence of the latter, residual pressure at the end of expiration is necessary in order to avoid the lung emptying itself of air. The resorption of pulmonary liquid from the alveolar spaces into the blood is dependent upon a change in the permeability of the alveolar epithelium, which renders possible the rapid passage of water via the channels which open, probably between the epithelial cells, and this change is dependent upon an expansion of the lungs by a pressure of between 35 and 40 cm H2O. Dilatation of the pulmonary vessels depends in part upon an increase in partial pressure of oxygen and a fall in carbon dioxide in the environment of the pulmonary arterioles, and in part upon mechanical changes brought about by the movements of ventilatation.

Humans↗
PubMed1974

Ion fluxes across the pulmonary epithelium and the secretion of lung liquid in the foetal lamb.

1. Experiments were done on exteriorized foetal lambs of 123-144 days gestation to measure bidirectional ion fluxes through the pulmonary epithelium and to compare them with those predicted from the sum of the measured forces determining passive flux according to the Ussing flux-ratio equation. Fluxes of Li(+), Na(+), K(+), Rb(+), Cs(+), Mg(2+), Ca(2+), Sr(2+), Ba(2+), Cl(-), Br(-) and I(-) were measured and permeability constants obtained by following concentrations of their labelled isotopes in lung liquid and plasma after injection into either. Activity ratios were obtained from chemical measurements or tracer distributions, electrical potential differences by placing KCl-agar bridges, connected to calomel half-cells, in blood and lung liquid. Lung liquid volume and secretion rate were measured by adding an impermeant tracer (inulin or [(125)I]albumin) to lung liquid.2. The permeability sequence of the pulmonary epithelium for alkali metals was, Na(+) > K(+) > Rb(+) > Li(+) > Cs(+) and that for halides I(-) approximately Br(-) > Cl(-). Permeabilities to alkaline earths were lower than for the other ions, no definite sequence being established.3. There was an electrical potential difference of -1 to -10 mV (mean -4.3 mV) between lung liquid and plasma (lung liquid negative). Plasma/lung liquid chemical activity ratios were less than unity for the halides (Cl(-), Br(-), I(-)), and for K(+) and Rb(+), whereas the ratio of one-way fluxes (plasma --> lung liquid)/(lung liquid --> plasma) was in each case greater than unity. From the difference between the measured flux ratios and those predicted from the forces determining passive flux, it was concluded that the halides, K(+) and Rb(+) were actively transported from plasma to lung liquid, Cl(-) being quantitatively the most important. Na(+) and Ca(2+) appeared to move passively down a gradient of electrochemical potential.4. When alveolar liquid [HCO(3) (-)] was artificially raised, a net flux of HCO(3) (-) from lung liquid against a gradient of electrochemical activity was observed, suggesting active transport of that ion out of lung liquid.5. The addition of KCN to lung liquid stopped the secretion of liquid and absorption took place.

Albumins↗
PubMed1973

Foetal medicine.

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Erythroblastosis, Fetal↗