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A Surface Phase Model of the Alveolar Lining: Ultrastructural Analysis and in vivo Applications

Larsson, Marcus LU (2002)
Abstract
In this thesis the relation between lung surfactant structure and functional properties have been studied.



Experimental results show that the alveolar surface is formed by a coherent surface phase with a structure equal to tubular myelin. The properties of this phase may explain certain unresolved issues in lung physiology, e.g., mechanical stability of surfactant during the breathing cycle, the question of free water in the alveolus, and uptake kinetics of pulmonary administered drugs. A surface phase has important consequences in general for the barrier function of the lung, and for host defense.



This surface phase is modeled with a biomathematical approach and is proposed to have a bilayer structure... (More)
In this thesis the relation between lung surfactant structure and functional properties have been studied.



Experimental results show that the alveolar surface is formed by a coherent surface phase with a structure equal to tubular myelin. The properties of this phase may explain certain unresolved issues in lung physiology, e.g., mechanical stability of surfactant during the breathing cycle, the question of free water in the alveolus, and uptake kinetics of pulmonary administered drugs. A surface phase has important consequences in general for the barrier function of the lung, and for host defense.



This surface phase is modeled with a biomathematical approach and is proposed to have a bilayer structure of a minimal surface type, the so-called CLP surface. This structure corresponds to a surfactant bilayer without self-intersections. The functional and structural properties of the CLP surface may explain e.g., the ultra low surface energy of surfactant in vivo, and rapid deformability of the surface phase during breathing.



The role of cholesterol in lung surfactant was studied by X-ray diffraction. It was shown that the presence of cholesterol lowers the crystallization temperature of the surfactant significantly.



During work with a pharmacy-grade lung surfactant, a novel dynamic swelling behavior was observed. During swelling in electrolyte containing water solutions, a dramatic increase of the air-water surface area was seen. In vivo evaluation of this process in an ARDS model was performed, showing significantly higher arterial oxygen levels in rats treated with surfactant in dynamic swelling compared to normal surfactant therapy. (Less)
Please use this url to cite or link to this publication:
author
opponent
  • Professor Gil, Jesus Perez, Dept. Bioquimica, Fac. Biologia, Universidad Complutense de Madrid 28040 Madrid, Spain
organization
publishing date
type
Thesis
publication status
published
subject
keywords
X-ray diffraction, cryo-TEM, dynamic swelling, ARDS, surface phase, surfactant replacement therapy, cholesterol, minimal surface, pulmonary surfactant, alveolar surface, Physiology, Fysiologi
pages
103 pages
publisher
Marcus Larsson, N. Vallg. 4, 223 62 Lund, Sweden,
defense location
Föreläsningssalen, Ingång 73, Plan 1 UMAS, Malmö
defense date
2002-12-06 09:15
ISBN
91-628-5448-8
language
English
LU publication?
yes
id
0b8fb097-ea7d-4d6e-9ddf-68705811c571 (old id 465163)
date added to LUP
2007-10-02 13:53:34
date last changed
2016-09-19 08:45:14
@misc{0b8fb097-ea7d-4d6e-9ddf-68705811c571,
  abstract     = {In this thesis the relation between lung surfactant structure and functional properties have been studied.<br/><br>
<br/><br>
Experimental results show that the alveolar surface is formed by a coherent surface phase with a structure equal to tubular myelin. The properties of this phase may explain certain unresolved issues in lung physiology, e.g., mechanical stability of surfactant during the breathing cycle, the question of free water in the alveolus, and uptake kinetics of pulmonary administered drugs. A surface phase has important consequences in general for the barrier function of the lung, and for host defense.<br/><br>
<br/><br>
This surface phase is modeled with a biomathematical approach and is proposed to have a bilayer structure of a minimal surface type, the so-called CLP surface. This structure corresponds to a surfactant bilayer without self-intersections. The functional and structural properties of the CLP surface may explain e.g., the ultra low surface energy of surfactant in vivo, and rapid deformability of the surface phase during breathing.<br/><br>
<br/><br>
The role of cholesterol in lung surfactant was studied by X-ray diffraction. It was shown that the presence of cholesterol lowers the crystallization temperature of the surfactant significantly.<br/><br>
<br/><br>
During work with a pharmacy-grade lung surfactant, a novel dynamic swelling behavior was observed. During swelling in electrolyte containing water solutions, a dramatic increase of the air-water surface area was seen. In vivo evaluation of this process in an ARDS model was performed, showing significantly higher arterial oxygen levels in rats treated with surfactant in dynamic swelling compared to normal surfactant therapy.},
  author       = {Larsson, Marcus},
  isbn         = {91-628-5448-8},
  keyword      = {X-ray diffraction,cryo-TEM,dynamic swelling,ARDS,surface phase,surfactant replacement therapy,cholesterol,minimal surface,pulmonary surfactant,alveolar surface,Physiology,Fysiologi},
  language     = {eng},
  pages        = {103},
  publisher    = {ARRAY(0x9d14110)},
  title        = {A Surface Phase Model of the Alveolar Lining: Ultrastructural Analysis and in vivo Applications},
  year         = {2002},
}