Maturational changes in responses of tissue and airway resistance
to histamine.
Dreshaj, Ismail A., Musa A. Haxhiu, Charles F. Potter, Faton H. Agani,
Richard J. Martin.
Department of Medicine, School of Medicine, Case Western Reserve
University, 10900 Euclid Avenue, Cleveland, Ohio 44106,
APStracts 3:0281A, 1996.
We determined how postnatal maturation affects the relative
contributions of airways and lung parenchyma to pulmonary resistance,
and whether there are developmental differences in their respective
responses to constrictive agents. We studied open-chested,
ventilated, anesthetized pigs at three ages: 2-4 days, 2-3 weeks, and
10 weeks. RL was partitioned into tissue (Rti) and airway (Raw)
resistance by means of alveolar capsules under baseline conditions
and following intravenous histamine. Postnatal maturation was
associated with a progressive decline in RL, Rti and Raw, and
increase in the contribution of Rti to RL from 38+/-8% at 2-4 days to
72+/-2% at both 2-3 and 10 weeks. Histamine caused RL to increase at
all ages. When partitioned into Rti and Raw, the percent increase in
Rti significantly exceeded that of Raw at both 2-4 days and 2-3
weeks. In contrast, the percent increase in Raw significantly
exceeded that of Rti at 10 weeks. Administration of atropine prior to
histamine in pigs at 10 weeks reduced the response of tissue and
airway resistance to histamine. Histamine-induced responses of RL
were blocked by prior H1 receptor blockade with pyrilamine (2 mg/kg).
These results indicate that 1) the contribution of Rti and Raw to RL
changes during maturation, and 2) contractile responses to exogenous
histamine are manifest predominantly in most distal airways and lung
parenchyma during early postnatal life; with advancing maturation
there is greater contribution of airways to the increase in RL
induced by histamine.
Received 31 July 1995; accepted in final form 31 May 1996.
APS Manuscript Number A838-5.
Article publication pending Journal of Applied Physiology.
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 28 June 96