Am. J. Respir. Crit. Care Med., Vol 149, No. 3, Mar 1994, 682-686.
Refractoriness of eucapnic hyperventilation-induced bronchoconstriction in rabbits
A Ohtsuka, S Koyama and T Horie
First Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan.
The mechanism of refractoriness in bronchoconstriction after repeated
hyperventilation was investigated in 18 sensitized rabbits. Rabbits were
separated into three groups: an untreated control group (n = 7), a
cimetidine-treated group (n = 6), and an indomethacin-treated group (n =
5). After anesthetization, hyperventilation was performed for 15 min (120
breaths/min, 7 ml/kg tidal volume) with dry air containing 5% CO2. Total
lung resistance (RL) and dynamic compliance (Cdyn) were measured before
(baseline) and after hyperventilation challenge. After RL and Cdyn had
returned to baseline values, the hyperventilation challenge was repeated.
In the control group maximal increase in percent RL (max %RL) was 49 +/- 9%
after the first challenge, but 16 +/- 4% after the second challenge,
indicating refractoriness. A similar tendency was observed in percent Cdyn.
In the cimetidine- and indomethacin-treated groups, max %RL were 42 +/- 3%
and 60 +/- 15% after the first challenge, and 35 +/- 8% and 60 +/- 7% after
the second challenge, respectively, indicating no refractoriness. These
results suggest that the H2-receptor and bronchodilating prostanoids play
an important role in producing the refractoriness to bronchoconstriction
observed in sensitized rabbits after repeated hyperventilation.