Fig. 4.
(A) Example in one urethane-sedated rat of the effects of an infusion of fentanyl (2.5 µg · kg-1 · min-1) maintained until an apnea is produced followed by the injection of naloxone (N, 2 mg · kg-1) that was administered while the animal still displayed a significant pulse pressure and sustained mean blood pressure. From top to bottom, instantaneous inspiratory flow (), carotid arterial blood pressure (BP), body temperature (T), minute ventilation (), mean arterial blood pressure (MBP), and carbon dioxide output () are displayed. The values of arterial pH, Pao2, Paco2, bicarbonate (HCO3-), base excess (BE), and lactate are also displayed. Note that (1) naloxone could not rescue the apnea produced by fentanyl; (2) a severe hypoxemia was present at the time of naloxone administration; and (3) the evolution was fatal despite a persistent arterial blood pressure signal for several minutes after naloxone injection. (B) Example of the effects of an infusion of fentanyl (2.5 µg · kg-1 · min-1) aimed at producing an apnea in a urethane-sedated rat exposed to hyperoxia. As in (A), naloxone (2 mg · kg-1) was administered within seconds after the onset of the apnea. Same legend as in (A). Note that naloxone rescued the apnea produced by fentanyl. (C) , / ratio, and mean blood pressure (individual data and median) are displayed in baseline condition (B), 30 s before naloxone injection (before N) and 1 min after naloxone (after N) during moderate fentanyl exposure (infusion maintained until minute ventilation decreased by half), or high level of exposure (infusion maintained until apnea) in air or hyperoxia. The P values of all significant differences are shown. The P values that are displayed with no symbols were obtained using the Friedman test (comparison within each group). Comparisons between groups were performed using a Kruskal–Wallis test followed by a Mann–Whitney U test for comparison between groups (&, comparison between high and low dose fentanyl in air at the same time point; $, comparison between air and hyperoxia at the same time point; *, comparison between air and hyperoxia at the same time point).