The effects of two common injectable laboratory anesthetics on the regulation of augmented (‘sigh’) breaths

Abstract

In this study, we investigated whether the link that we have recently established between hypocapnia and AB production is only observable in unanesthetized animals, possibly explaining why other laboratories using anesthetized preparations have not also reported this obvious effect. Ten male rats were studied on three separate days, receiving one of three injections each day in randomized order: ethyl carbamate (‘urethane’; 1.2 mg·kg−1); a ketamine/xylazine combination (ket/xyl; 80/10 mg·kg−1), or normal saline (control). Following each of the three interventions, breathing was monitored during 15 minute exposures to normoxia (room air), hypoxia (10% O2) and hypoxia+CO2 (10% O2, 5% CO2). Urethane anesthesia completely eliminated ABs from the breathing rhythm in room air conditions (0.0 ± 0.0 vs 4.0 ± 1.8 ABs·15min−1 in saline control, P<0.001), and decreased the hypocapnia‐dependent component of the hypoxia‐induced facilitation of ABs (p<0.001). Ket/xyl left the normal incidence of ABs in room air breathing intact (4.5 ± 2.2 ABs·15min−1, p=0.689 vs. saline control) but significantly suppressed the hypoxia‐induced facilitation of ABs (Δ = 9.6 ± 6.1 vs 32.7 ± 14.4 ABs·15min−1 in saline control, p=0.0015). Our results provide the first clear evidence that laboratory anesthesia can profoundly alter the regulation of ABs including the hypocapnia‐dependent component of their facilitation. This research was supported by laboratory research start‐up funds provided by the Department of Medicine, Penn State College of Medicine. JM was supported in part through the SURIP program of the Department of Cellular and Molecular Physiology of Penn State University.