An In Vivo Anesthetic Model of Autoresuscitation Failure in Adult Rats

Abstract

In studying the cardiorespiratory response to acute severe hypoxia, we observed that urethane anesthesia had deleterious effects on respiratory autoresuscitation. To investigate this effect further, we assessed the cardiorespiratory response to anoxia‐induced respiratory arrest (RA) in 3 groups of anesthetized, spontaneously breathing adult male rats. Three common injectables were used to achieve a surgical plane of anesthesia: ketamine‐xylazine (KET, n=10), pentobarbital (PEN, n=10), and urethane (URE, n=10). All KET and PEN animals successfully resuscitated from 4 consecutive RAs. In stark contrast, none of the URE animals were able to mount a successful autoresuscitation. Interestingly, only 4/10 URE animals were capable of expressing resuscitating breaths following the onset of RA. Arterial PO2 at RA was not different across groups (avg = 12.1 ± 2.6 mmHg). Duration of primary apnea was longest in the URE animals (141.90 ± 19.38) compared to either KET (54.30 ± 6.96) or PEN (68.35 ± 12.87) animals. The average and largest volumes of resuscitating breaths were smaller in the URE condition compared to either KET or PEN. These alterations are suggestive of a profound alteration of central control over switching between modes of respiratory rhythm generation. URE animals showed no clear aberrations in their cardiovascular responses to anoxia, with the exception of lower arterial pulse pressures compared to either KET or PEN animals at specific points following RA. Our results suggest that urethane anesthesia may provide a valuable model of catastrophic failure of the autoresuscitation process that will enable identification of physiological and neurobiological factors that predispose some individuals to sudden death during an acute bout of asphyxia.