TY - JOUR
T1 - Changes in lung permeability and lung mechanics accompany homeostatic instability in senescent mice
AU - Tankersley, Clarke G.
AU - Shank, Jessica A.
AU - Flanders, Susan E.
AU - Soutiere, Shawn E.
AU - Rabold, Richard
AU - Mitzner, Wayne
AU - Wagner, Elizabeth M.
PY - 2003/10/1
Y1 - 2003/10/1
N2 - Aging and lung disease are recognized factors that increase mortality risk in subjects exposed to ambient particulate matter (PM). In an effort to understand the mechanisms of enhanced susceptibility, the present study examined an inbred mouse model of senescence to 1) determine changes in lung permeability as animals approach the end-of-life and 2) characterize age-dependent changes in lung mechanics in presenescent and terminally senescent mice. The clearance of technetium-99m ( 99mTc)-diethylenetriamine pentaacetic acid (DTPA) was used to test the hypothesis that lung permeability increases with age and enhances uptake of soluble components of PM principally during the period several weeks before death in AKR/J mice. Quasistatic pressure-volume curves were conducted on robust and on terminally senescent AKR/J mice several weeks before death to assess the relative importance of lung mechanics. Abrupt body weight loss was used to signal imminent death because it accompanies indexes of physiological aging and terminal senescence. 99mTc-DTPA clearance from the lung 30 min after tracheal instillation was significantly (P < 0.05) enhanced in senescent mice. Age-dependent changes in lung mechanics were indicative of significant (P < 0.05) decrements in lung volume and compliance several weeks before death. Thus, during a period of homeostatic instability leading toward natural death, AKR/J mice showed enhanced permeability of soluble particles despite a decrease in lung volume and concomitant alveolar surface area. These results suggest that pulmonary epithelial-endothelial barrier dysfunction occurs in terminally senescent mice just before death. Furthermore, this senescent-dependent increase in lung permeability may be a contributing factor for increased PM susceptibility in the elderly and patients with lung disease.
AB - Aging and lung disease are recognized factors that increase mortality risk in subjects exposed to ambient particulate matter (PM). In an effort to understand the mechanisms of enhanced susceptibility, the present study examined an inbred mouse model of senescence to 1) determine changes in lung permeability as animals approach the end-of-life and 2) characterize age-dependent changes in lung mechanics in presenescent and terminally senescent mice. The clearance of technetium-99m ( 99mTc)-diethylenetriamine pentaacetic acid (DTPA) was used to test the hypothesis that lung permeability increases with age and enhances uptake of soluble components of PM principally during the period several weeks before death in AKR/J mice. Quasistatic pressure-volume curves were conducted on robust and on terminally senescent AKR/J mice several weeks before death to assess the relative importance of lung mechanics. Abrupt body weight loss was used to signal imminent death because it accompanies indexes of physiological aging and terminal senescence. 99mTc-DTPA clearance from the lung 30 min after tracheal instillation was significantly (P < 0.05) enhanced in senescent mice. Age-dependent changes in lung mechanics were indicative of significant (P < 0.05) decrements in lung volume and compliance several weeks before death. Thus, during a period of homeostatic instability leading toward natural death, AKR/J mice showed enhanced permeability of soluble particles despite a decrease in lung volume and concomitant alveolar surface area. These results suggest that pulmonary epithelial-endothelial barrier dysfunction occurs in terminally senescent mice just before death. Furthermore, this senescent-dependent increase in lung permeability may be a contributing factor for increased PM susceptibility in the elderly and patients with lung disease.
KW - Air pollution susceptibility
KW - Diethylenetriamine pentaacetic acid clearance in mice
KW - Epithelial-endothelial barrier dysfunction
KW - Particulate matter
KW - Physiological aging
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U2 - 10.1152/japplphysiol.00190.2003
DO - 10.1152/japplphysiol.00190.2003
M3 - Article
C2 - 12794030
AN - SCOPUS:0141790266
SN - 8750-7587
VL - 95
SP - 1681
EP - 1687
JO - Journal of applied physiology
JF - Journal of applied physiology
IS - 4
ER -