EFFECT OF CHRONIC RESISTIVE LOADING ON VENTILATORY CONTROL IN A RAT MODEL

Acute resistive loading of the airway has been shown to activate the e ndogenous opioid system, with subsequent depression of ventilation. Th e present investigation was designed to assess the effect of chronic a irway loading on ventilation and CO2 sensitivity, and to determine whe ther the endogenous opioid system contributes to long-term modulation of ventilatory control in this setting. A Row-resistive ventilatory lo ad was imposed in 2-mo-old rats by surgical implantation of a circumfe rential tracheal band that approximately tripled tracheal resistance. Respiration and CO2 ensitivity were serially and noninvasively assesse d by barometric plethysmography over a period of 21 wk. Ventilatory ou tput was assessed as minute inspiratory effort, which was defined as t he product of plethysmograph signal amplitude, inspiratory time, and r espiratory tate (RR). CO2 ensitivity was calculated as the percent cha nge in minute inspiratory effort from room air to CO2 exposure. The ef fect of naloxone administration on these parameters was also determine d. Arterial blood gases demonstrated hypercapnia with maintenance of n ormoxia in loaded rats; these findings persisted for the duration of t he study. Two days after surgery, rats with tracheal obstruction demon strated a lower RR than controls during room air breathing and during CO2 stimulation. CO2 sensitivity was significantly depressed in obstru cted anials at this time. Escape from suppression of RR and CO2 sensit ivity was evident by 14 to 21 d after obstruction; however, suppressio n of these parameters reappeared and was maintained from 56 to 147 d a fter 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 me chanisms that do not involve endogenous opioids.