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1 Department of Biomedical Engineering, Boston University, Boston, Massachusetts 02215 and 2 Department of Pharmacology, Boehringer Ingelheim Pharmaceuticals, Ridgefield, Connecticut 06877
Ascaris
suum (AS) challenge in nonhuman primates is used as an animal
model of human asthma. The primary goal of this study was to determine
whether the airways and respiratory tissues in monkeys that are
bronchoconstricted by AS inhalation behave similarly to those in
asthmatic humans. Airway resistance (Raw) and tissue elastance (Eti)
were estimated from respiratory system input (Zin) or transfer (Ztr)
impedance. Zin (0.4-20 Hz) and Ztr (2-128 Hz) were measured
in anesthetized cynomolgus monkeys (n = 10) under baseline (BL) and post-AS challenge conditions. Our results indicate that AS challenge in monkeys produces 1) predominately an
increase in Raw and not tissue resistance, 2) airway wall
shunting at higher AS doses, and 3) heterogeneous airway
constriction resulting in a decrease of lung parenchyma effective
compliance. We investigated whether the airway and tissue properties
estimated from Zin and Ztr were similar and found that Raw estimated
from Zin and Ztr were correlated [r2 = 0.76], not significantly different at BL (13.6 ± 1.4 and
13.1 ± 0.9 cmH2O · l
1 · s
1,
respectively), but significantly different post-AS (20.5 ± 4.5 cmH2O · l
1 · s
1
and 18.5 ± 5.2 cmH2O · l
1 · s
1).
There was no correlation between Eti estimated from Zin and Ztr. The
changes in lung mechanical properties in AS-bronchoconstricted monkeys
are similar to those recently reported in human asthma, confirming that
this is a reasonable model of human asthma.
lung tissue resistance; lung tissue compliance; respiratory mechanics
This article has been cited by other articles:
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R. L. Coffman and E. M. Hessel Nonhuman primate models of asthma J. Exp. Med., June 20, 2005; 201(12): 1875 - 1879. [Abstract] [Full Text] [PDF] |
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