Fig. 5.
Coadministration of ABT 594 reduced fentanyl- or remifentanil-induced respiratory depression and apneas. (A) Coadministration of fentanyl (12 µg/kg over 1 min, iv infusion) with saline vehicle (1 min iv infusion) caused a marked progressive respiratory depression in respiratory frequency and tidal volume, leading to profound apneas in a rat. (B) In another cohort, coadministration of fentanyl (12 µg/kg over 1 min, iv infusion) with saline vehicle (1 min iv infusion) caused marked initial apneas, with a quick recovery in respiratory frequency in a rat. (C) Coadministration of fentanyl (12 µg/kg over 1 min, iv infusion) with ABT 594 (20 µg/kg over 1 min, iv infusion) alleviated fentanyl-induced decrease in respiratory frequency, with fewer effects on fentanyl-induced initial apneas and no effect on the reduction of tidal volume in a rat. (D) Coadministration of remifentanil (5 µg/kg over 20 s, iv) and saline (iv) caused a marked respiratory depression and apneas. (E) Coadministration of remifentanil (5 µg/kg over 20 s, iv) with ABT 594 (20 µg/kg over 20 s, iv) alleviated remifentanil-induced respiratory depression and apneas. Population data (median and interquartile ranges for F; mean and SD for G) showing coadministration of ABT 594 (20 µg/kg, iv) decreases duration of apneas induced by fentanyl (F) or remifentanil (G). *P < 0.05, statistically significant difference compared with saline group, using Mann–Whitney rank sum Test for fentanyl (F), and independent t test for remifentanil (G). n = 7 animals for each group.