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Development and regulation of alveolar fluid clearance in the guinea pig

Norlin, Andreas LU (2000)
Abstract (Swedish)
Popular Abstract in Swedish

För att lungorna ska utvecklas normalt hos ett däggdjursfoster, måste lungorna vara vätskefyllda. Det har länge varit kännt att denna vätska produceras av lungorna själva, genom s k klorid-sekretion. Vid födelsen måste det nyfödda fostret börja andas och därför är det ytterst viktigt att lungorna snabbt töms på vätskan som fanns där under fosterutvecklingen. Detta sker till stor del genom att lungorna absorberar, d v s “suger upp”, vätskan som därefter transporteras bort med blodet. Denna funktion finns även i fullt utvecklade, vuxna lungor. Vi studerade vid vilken tidpunkt hos marsvin lungorna börjar absorbera vätska och fann att de normalt absorberar lungvätska några dagar innan födelsen,... (More)
Popular Abstract in Swedish

För att lungorna ska utvecklas normalt hos ett däggdjursfoster, måste lungorna vara vätskefyllda. Det har länge varit kännt att denna vätska produceras av lungorna själva, genom s k klorid-sekretion. Vid födelsen måste det nyfödda fostret börja andas och därför är det ytterst viktigt att lungorna snabbt töms på vätskan som fanns där under fosterutvecklingen. Detta sker till stor del genom att lungorna absorberar, d v s “suger upp”, vätskan som därefter transporteras bort med blodet. Denna funktion finns även i fullt utvecklade, vuxna lungor. Vi studerade vid vilken tidpunkt hos marsvin lungorna börjar absorbera vätska och fann att de normalt absorberar lungvätska några dagar innan födelsen, vilket tyder på att lungorna redan då har börjat förbereda sig för den kommande uppgiften att andas luft. Vidare fann vi att hastigheten hos vätske-absorptionen snabbt ökade vid födelsen och att i nyfödda marsvin kunde ungefär 60% av en testlösning som sprutats ner i lungorna absorberas på en timme. Några dagar efter födelsen var vätske-absorptionen i lungorna på samma nivå som i vuxna lungor. Vi kunde också visa att vätske-absorptionen i vuxna lungor kunde stimuleras (öka absorptionshastigheten) med stresshormonet, adrenalin. Förutom att adrenalin kunde stimulera vätske-absorptionen, så fann vi i våra studier att ett annat stresshormon, kortisol (hydrokortison), var viktigt för att vidmakthålla den relativt höga förmågan att absorbera vätska i vuxna marsvinslungor. Vi fann också att kalcium-jonbalansen i och kring lungans celler var viktig för att adrenalin-liknande ämnen skulle stimulera vätske-absorptionen. Vätske-absorptionen i lungorna sker genom en mekanism som kortfattat innebär att vatten förflyttas från yttersidan (luftsidan) till insidan (blodsidan) av det s k epitelcell-lagret (det yttersta cell-lagret som gränsar mot luften i lungorna), som en följd av att natriumklorid (vanligt koksalt) transporteras över epitelet. Processen är snarlik den som sker i njurarna och i tjocktarmen när vätska absorberas. Av största vikt för absorptionen är att det finns s k natrium-kalium-pumpar och natrium-kanaler i epitelcellerna, som tillsammans transporterar natriumjoner från epitelcell-lagrets luftsida till blodsida. I våra studier fann vi att en viss typ av natrium-kanaler, som kallas ENaC, var mycket talrika precis när lungorna började utveckla vätske-absorptionen. Framförallt, fanns det stora mängder av dessa kanaler i nyfödda lungor, men efter födelsen minskade kanalerna i antal. Det viktigaste resultatet från dessa studier var att vi genom att starta förlossnings-arbetet hos dräktiga marsvin kunde förmå fostrens lungor att absorbera vätska långt tidigare än vad som är normalt. Denna inducerade vätske-absorption var tillstörsta delen beroende av ENaC-natrium-kanalen. Resultaten visar tydligt att värkarbetet, som bl a yttrar sig i sammandragningar av livmodern, är viktigt för att lungorna ska slutgiltigt anpassa sig för luftandning. Vid fördjupade studier av värkarbetets betydelse för vätske-absorptionen i fosterlungorna, fann vi att värkarbetet (troligtvis p g a livmoderns sammandragningar) medförde att fostrens adrenalin-nivåer ökade mycket kraftigt. Adrenalinet i sin tur stimulerade vätske-absorptionen. Sammantaget, har vi i dessa studier fördjupat förståelsen och kunskaperna om lungans vätske-absorption, framförallt hos foster och nyfödda, men även hos vuxna djur. I förlängningen kan detta leda till ett förbättrat omhändertagande och behandling av förtidigt födda barn, i synnerhet för de som är förlösta med kejsarsnitt innan värkarbetet har startat. Även för behandlingen av vuxna individer som lider av lungödem (vätskeansamlingar i lungan) bör dessa rön i framtiden kunna leda till nya och förbättrade behandlingsmetoder. (Less)
Abstract
Alveolar fluid clearance is driven by active absorption of Na+ across the alveolar epithelium. Development and hormonal regulation of alveolar fluid clearance over 1 hour was studied by instillation of a protein-containing, isosmolar fluid into lungs of fetal, newborn, and adult guinea pigs. After 1 hour, a sample of remaining alveolar fluid was collected and the change in protein concentration was used to calculate secretion or absorption of fluid. The technique is based on the principle that large molecules cross the alveolar epithelium at a much slower rate than water, and as such, a change in concentration reflects water movement across the cell layer. At 61 days gestation (term = 69 days), the guinea pig lung secreted fluid into the... (More)
Alveolar fluid clearance is driven by active absorption of Na+ across the alveolar epithelium. Development and hormonal regulation of alveolar fluid clearance over 1 hour was studied by instillation of a protein-containing, isosmolar fluid into lungs of fetal, newborn, and adult guinea pigs. After 1 hour, a sample of remaining alveolar fluid was collected and the change in protein concentration was used to calculate secretion or absorption of fluid. The technique is based on the principle that large molecules cross the alveolar epithelium at a much slower rate than water, and as such, a change in concentration reflects water movement across the cell layer. At 61 days gestation (term = 69 days), the guinea pig lung secreted fluid into the future air spaces of the lungs. Between 64 and 66 days gestation, alveolar fluid clearance slowly begun to develop and then rapidly increased to a maximal level at birth (62 ± 5% of the instilled fluid was absorbed over one hour). Alveolar fluid clearance then decreased to adult levels (37 ± 5% fluid absorption) within a few days after birth. Preterm and neonatal, but not adult alveolar fluid clearance depended on endogenous epinephrine stimulation. Alveolar fluid clearance could be stimulated with exogenous â-adrenergic agonists in the lung by stimulation of â1-adrenergic receptors, when there was no endogenous- adrenergic stimulation. The adult basal alveolar fluid clearance was maintained at a relatively high rate by endogenous cortisol, which functioned by continuously stimulating áENaC (epithelial Na+ channel subunit) mRNA transcription and de novo ENaC protein synthesis. Oxytocin-induced preterm labor induced alveolar fluid clearance at 61 days gestation, when there normally was fluid secretion. Since propranolol inhibited this effect and the fetal plasma epinephrine levels were increased, oxytocin acted through release of endogenous epinephrine.Basal and stimulated alveolar fluid clearance was always sensitive to amiloride-instillation (ENaC inhibitor) at all ages when there was fluid absorption. Preterm alveolar fluid clearance was almost completely inhibited by amiloride; the sensitivity decreased with age, and alveolar fluid clearance in adult guinea pigs was inhibited by around 40%. Development of áENaC mRNA expression and amiloride-sensitivity suggested that ENaC represented a major pathway for alveolar fluid clearance before birth and that alternative pathways for alveolar fluid clearance developed in the postnatal lungs. Since, the amiloride-sensitive fraction of alveolar fluid clearance was not different from that in control guinea pigs after â-adrenergic stimulation of alveolar fluid clearance, both amiloride-sensitive and amiloride-insensitive pathways were simultaneously stimulated. â-adrenergic stimulation of alveolar fluid clearance was mediated by intracellular cAMP as a second messenger. Also, intracellular Ca2+ concentration changes inhibited both stimulated and basal alveolar fluid clearance, at all ages, suggesting that disturbance of normal intracellular Ca2+ concentrations may affect Na+ transport pathways. IN CONCLUSION: The major findings in this study were that an amiloride-sensitive alveolar fluid clearance can be induced in otherwise fluid-secreting lungs by oxytocin-induced preterm labor. These results may be important for the survival and health of prematurely born infants and infants delivered by emergency cesarean section, especially if cesarean-delivered before the start of labor, since these infants frequently display a respiratory distress that may be related to immature fluid absorption. (Less)
Please use this url to cite or link to this publication:
author
opponent
  • Prof Nicolaysen, Gunnar, Department of Physiology; University of Oslo, Norway
organization
publishing date
type
Thesis
publication status
published
subject
keywords
oxytocin-induced preterm labor, IRDS, fetal lung fluid, preterm lung development, amiloride-sensitive sodium channels, beta-adrenergic stimulation, alveolar epithelium, Animal physiology, Djurfysiologi
pages
121 pages
publisher
Department of Animal Physiology, Lund University
defense location
Hörsalen at Department of Animal Physiology
defense date
2000-12-15 10:15
external identifiers
  • Other:ISRN: LUNBDS/(NBZF/1056)/1-64 (2000)
ISBN
91-628-4517-9
language
English
LU publication?
yes
id
afeff9a2-bb73-44aa-a129-d3cca3a4c16a (old id 41113)
date added to LUP
2007-07-31 14:15:11
date last changed
2016-09-19 08:45:06
@misc{afeff9a2-bb73-44aa-a129-d3cca3a4c16a,
  abstract     = {Alveolar fluid clearance is driven by active absorption of Na+ across the alveolar epithelium. Development and hormonal regulation of alveolar fluid clearance over 1 hour was studied by instillation of a protein-containing, isosmolar fluid into lungs of fetal, newborn, and adult guinea pigs. After 1 hour, a sample of remaining alveolar fluid was collected and the change in protein concentration was used to calculate secretion or absorption of fluid. The technique is based on the principle that large molecules cross the alveolar epithelium at a much slower rate than water, and as such, a change in concentration reflects water movement across the cell layer. At 61 days gestation (term = 69 days), the guinea pig lung secreted fluid into the future air spaces of the lungs. Between 64 and 66 days gestation, alveolar fluid clearance slowly begun to develop and then rapidly increased to a maximal level at birth (62 ± 5% of the instilled fluid was absorbed over one hour). Alveolar fluid clearance then decreased to adult levels (37 ± 5% fluid absorption) within a few days after birth. Preterm and neonatal, but not adult alveolar fluid clearance depended on endogenous epinephrine stimulation. Alveolar fluid clearance could be stimulated with exogenous â-adrenergic agonists in the lung by stimulation of â1-adrenergic receptors, when there was no endogenous- adrenergic stimulation. The adult basal alveolar fluid clearance was maintained at a relatively high rate by endogenous cortisol, which functioned by continuously stimulating áENaC (epithelial Na+ channel subunit) mRNA transcription and de novo ENaC protein synthesis. Oxytocin-induced preterm labor induced alveolar fluid clearance at 61 days gestation, when there normally was fluid secretion. Since propranolol inhibited this effect and the fetal plasma epinephrine levels were increased, oxytocin acted through release of endogenous epinephrine.Basal and stimulated alveolar fluid clearance was always sensitive to amiloride-instillation (ENaC inhibitor) at all ages when there was fluid absorption. Preterm alveolar fluid clearance was almost completely inhibited by amiloride; the sensitivity decreased with age, and alveolar fluid clearance in adult guinea pigs was inhibited by around 40%. Development of áENaC mRNA expression and amiloride-sensitivity suggested that ENaC represented a major pathway for alveolar fluid clearance before birth and that alternative pathways for alveolar fluid clearance developed in the postnatal lungs. Since, the amiloride-sensitive fraction of alveolar fluid clearance was not different from that in control guinea pigs after â-adrenergic stimulation of alveolar fluid clearance, both amiloride-sensitive and amiloride-insensitive pathways were simultaneously stimulated. â-adrenergic stimulation of alveolar fluid clearance was mediated by intracellular cAMP as a second messenger. Also, intracellular Ca2+ concentration changes inhibited both stimulated and basal alveolar fluid clearance, at all ages, suggesting that disturbance of normal intracellular Ca2+ concentrations may affect Na+ transport pathways. IN CONCLUSION: The major findings in this study were that an amiloride-sensitive alveolar fluid clearance can be induced in otherwise fluid-secreting lungs by oxytocin-induced preterm labor. These results may be important for the survival and health of prematurely born infants and infants delivered by emergency cesarean section, especially if cesarean-delivered before the start of labor, since these infants frequently display a respiratory distress that may be related to immature fluid absorption.},
  author       = {Norlin, Andreas},
  isbn         = {91-628-4517-9},
  keyword      = {oxytocin-induced preterm labor,IRDS,fetal lung fluid,preterm lung development,amiloride-sensitive sodium channels,beta-adrenergic stimulation,alveolar epithelium,Animal physiology,Djurfysiologi},
  language     = {eng},
  pages        = {121},
  publisher    = {ARRAY(0x97d87f8)},
  title        = {Development and regulation of alveolar fluid clearance in the guinea pig},
  year         = {2000},
}