EFFECTS OF MORPHINE AND PHYSOSTIGMINE ON THE VENTILATORY RESPONSE TO CARBON-DIOXIDE

Background: It has been reported that physostigmine antagonizes morphine-induced respiratory depression, but it is not known whether this is due to a central chemoreceptor effect, an effect on the peripheral chemoreflex loop, or both. We therefore assessed the effect of morphine and physostigmine on the normoxic hypercapnic ventilatory response mediated by the central and peripheral chemoreceptors in ten alpha-chloralose-urethan-anesthetized cats. Methods: The breath-by-breath ventilatory responses to stepwise changes in end-tidal CO2 tension were determined before (control), after administration of morphine hydrochloride (0.15 mg . kg(-1)) and during intravenous infusion of physostigmine salicylate (bolus of 0.05 mg . kg(-1) followed by 0.025 mg . kg(-1) . h(-1)). Each response was separated into a central and a peripheral chemoreflex characterized by CO2 sensitivity (S-c and S-p), time constant, time delay, and apneic threshold (a single off-set B). Results: Morphine increased B and decreased S-c and S-p (P < 0.01), but not the ratio S-p/S-c. Subsequent infusion of physostigmine decreased B (P < 0.01), without further change of S-p and S-c. Premedication with physostigmine decreased B, S-p and S-c (P < 0.01) vs. control, but not S-p/S-c. Subsequent administration of morphine decreased S-p and S-c further but increased B (P < 0.01), while S-p/S-c remained constant. Conclusions: Because morphine diminishes the S-c and S-p of the chemoreflex loop to the same extent this depressant effect is presumably due to an action on the respiratory integrating centers rather than on the peripheral and central chemoreceptors as such and is not antagonized by physostigmine. We argue that the increase in B may be due to changes in the amount of acetylcholine available in the brain and can be antagonized by physostigmine.