TY - JOUR
T1 - The fix is not yet in
T2 - recommendation for fixation of lungs within physiological/pathophysiological volume range in preclinical pulmonary structure-function studies
AU - Perlman, Carrie E.
AU - Knudsen, Lars
AU - Smith, Bradford J.
PY - 2024/8/1
Y1 - 2024/8/1
N2 - Quantitative characterization of lung structures by morphometrical or stereological analysis of histological sections is a powerful means of elucidating pulmonary structure-function relations. The overwhelming majority of studies, however, fix lungs for histology at pressures outside the physiological/pathophysiological respiratory volume range. Thus, valuable information is being lost. In this perspective article, we argue that investigators performing pulmonary histological studies should consider whether the aims of their studies would benefit from fixation at functional transpulmonary pressures, particularly those of end-inspiration and end-expiration. We survey the pressures at which lungs are typically fixed in preclinical structure-function studies, provide examples of conditions that would benefit from histological evaluation at functional lung volumes, summarize available fixation methods, discuss alternative imaging modalities, and discuss challenges to implementing the suggested approach and means of addressing those challenges. We aim to persuade investigators that modifying or complementing the traditional histological approach by fixing lungs at minimal and maximal functional volumes could enable new understanding of pulmonary structure-function relations.
AB - Quantitative characterization of lung structures by morphometrical or stereological analysis of histological sections is a powerful means of elucidating pulmonary structure-function relations. The overwhelming majority of studies, however, fix lungs for histology at pressures outside the physiological/pathophysiological respiratory volume range. Thus, valuable information is being lost. In this perspective article, we argue that investigators performing pulmonary histological studies should consider whether the aims of their studies would benefit from fixation at functional transpulmonary pressures, particularly those of end-inspiration and end-expiration. We survey the pressures at which lungs are typically fixed in preclinical structure-function studies, provide examples of conditions that would benefit from histological evaluation at functional lung volumes, summarize available fixation methods, discuss alternative imaging modalities, and discuss challenges to implementing the suggested approach and means of addressing those challenges. We aim to persuade investigators that modifying or complementing the traditional histological approach by fixing lungs at minimal and maximal functional volumes could enable new understanding of pulmonary structure-function relations.
KW - design-based stereology
KW - lung fixation
KW - morphometry
KW - pulmonary structure and function
UR - http://www.scopus.com/inward/record.url?scp=85199816032&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85199816032&partnerID=8YFLogxK
U2 - 10.1152/ajplung.00341.2023
DO - 10.1152/ajplung.00341.2023
M3 - Review article
C2 - 38712433
AN - SCOPUS:85199816032
SN - 1040-0605
VL - 327
SP - L218-L231
JO - American Journal of Physiology - Lung Cellular and Molecular Physiology
JF - American Journal of Physiology - Lung Cellular and Molecular Physiology
IS - 2
ER -