Am. J. Respir. Crit. Care Med., Vol 152, No. 2, 08 1995, 666-676.
Effect of chronic resistive loading on ventilatory control in a rat model [published erratum appears in Am J Respir Crit Care Med 1996 Jun;153(6 Pt 1):2028]
HE Greenberg, A Tarasiuk, RS Rao, M Kupferman, N Kane, SM Scharf and M] Kuperferman M [corrected to Kupferman
Division of Pulmonary and Critical Care Medicine, Long Island Jewish Medical Center, New Hyde Park, NY 10042, USA.
Acute resistive loading of the airway has been shown to activate the
endogenous opioid system, with subsequent depression of ventilation. The
present investigation was designed to assess the effect of chronic airway
loading on ventilation and CO2 sensitivity, and to determine whether the
endogenous opioid system contributes to long-term modulation of ventilatory
control in this setting. A flow-resistive ventilatory load was imposed in
2-mo-old rats by surgical implantation of a circumferential tracheal band
that approximately tripled tracheal resistance. Respiration and CO2
sensitivity were serially and noninvasively assessed by barometric
plethysmography over a period of 21 wk. Ventilatory output was assessed as
minute inspiratory effort, which was defined as the product of
plethysmograph signal amplitude, inspiratory time, and respiratory rate
(RR). CO2 sensitivity was calculated as the percent change in minute
inspiratory effort from room air to CO2 exposure. The effect of naloxone
administration on these parameters was also determine. Arterial blood gases
demonstrated hypercapnia with maintenance of normoxia in loaded rats; these
findings persisted for the duration of the study. Two days after surgery,
rats with tracheal obstruction demonstrated a lower RR than controls during
room air breathing and during CO2 stimulation. CO2 sensitivity was
significantly depressed in obstructed animals at this time. Escape from
suppression of RR and CO2 sensitivity was evident by 14 to 21 d after
obstruction; however, suppression of these parameters reappeared and was
maintained from 56 to 147 d after obstruction. Naloxone augmented minute
inspiratory effort during CO2 stimulation at 2 d after obstruction but not
thereafter; naloxone had no effect in control rats. These data indicate
that chronic airway loading suppresses RR and CO2 sensitivity in a
triphasic manner. The early suppression is partially reversible by
naloxone; late-appearing suppression is unaffected by naloxone and is
presumably mediated by mechanisms that do not involve endogenous opioids.
