TY - JOUR
T1 - Biaxial distension of precision-cut lung slices
AU - Dassow, C.
AU - Wiechert, L.
AU - Martin, C.
AU - Schumann, S.
AU - Müller-Newen, G.
AU - Pack, O.
AU - Guttmann, J.
AU - Wall, W. A.
AU - Uhlig, S.
PY - 2010/3
Y1 - 2010/3
N2 - The mechanical forces acting on lung parenchyma during (mechanical) ventilation and its (patho)physiological consequences are currently under intense scrutiny. Several in vivo and cell culture models have been developed to study the pulmonary responses to mechanical stretch. While providing extremely useful information, these models do also suffer from limitations in being either too complex for detailed mechanical or mechanistic studies, or in being devoid of the full complexity present in vivo (e.g., different cell types and interstitial matrix). Therefore in the present study it was our aim to develop a new model, based on the biaxial stretching of precision-cut lung slices (PCLS). Single PCLS were mounted on a thin and flexible carrier membrane of polydimethylsiloxane (PDMS) in a bioreactor, and the membrane was stretched by applying varying pressures under static conditions. Distension of the membrane-PCLS construct was modeled via finite element simulation. According to this analysis, lung tissue was stretched by up to 38% in the latitudinal and by up to 44% in the longitudinal direction, resulting in alveolar distension similar to what has been described in intact lungs. Stretch for 5 min led to increased cellular calcium levels. Lung slices were stretched dynamically with a frequency of 15/m.in for 4 h without causing cell injury {3-[4, 5dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) test; live/dead straining}. These findings suggest that stretching of PCLS on PDMS-membranes may represent a useful model to investigate lung stretch in. intact lung tissue in vitro for several hours.
AB - The mechanical forces acting on lung parenchyma during (mechanical) ventilation and its (patho)physiological consequences are currently under intense scrutiny. Several in vivo and cell culture models have been developed to study the pulmonary responses to mechanical stretch. While providing extremely useful information, these models do also suffer from limitations in being either too complex for detailed mechanical or mechanistic studies, or in being devoid of the full complexity present in vivo (e.g., different cell types and interstitial matrix). Therefore in the present study it was our aim to develop a new model, based on the biaxial stretching of precision-cut lung slices (PCLS). Single PCLS were mounted on a thin and flexible carrier membrane of polydimethylsiloxane (PDMS) in a bioreactor, and the membrane was stretched by applying varying pressures under static conditions. Distension of the membrane-PCLS construct was modeled via finite element simulation. According to this analysis, lung tissue was stretched by up to 38% in the latitudinal and by up to 44% in the longitudinal direction, resulting in alveolar distension similar to what has been described in intact lungs. Stretch for 5 min led to increased cellular calcium levels. Lung slices were stretched dynamically with a frequency of 15/m.in for 4 h without causing cell injury {3-[4, 5dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) test; live/dead straining}. These findings suggest that stretching of PCLS on PDMS-membranes may represent a useful model to investigate lung stretch in. intact lung tissue in vitro for several hours.
KW - Calcium
KW - Finite element simulation
KW - Lung stretch
KW - Strain
UR - http://www.scopus.com/inward/record.url?scp=77949594284&partnerID=8YFLogxK
U2 - 10.1152/japplphysiol.00229.2009
DO - 10.1152/japplphysiol.00229.2009
M3 - Article
C2 - 20075265
AN - SCOPUS:77949594284
SN - 8750-7587
VL - 108
SP - 713
EP - 721
JO - Journal of Applied Physiology
JF - Journal of Applied Physiology
IS - 3
ER -