Respiratory autoresuscitation following severe acute hypoxemia in anesthetized adult rats.

In the present study we investigated the pattern and efficacy of respiratory autoresuscitation in spontaneously breathing adult male rats across three separate anesthetic backgrounds. Each animal was administered one of three injectable anesthetics to achieve a surgical plane of anesthesia: ketamine-xylazine (KET, n=10), pentobarbital (PEN, n=10), or urethane (URE, n=10). Animals were tracheostomized and equipped with a femoral artery catheter to record airflow and arterial pressures. In response to a bout of breathing anoxic air, none of the 10 URE animals were able to mount a successful autoresuscitation response. In contrast, all KET and PEN animals survived all four consecutive anoxic exposures, restoring eupneic breathing in all cases. Moreover, only 4/10 URE animals expressed gasping breaths following the onset of respiratory arrest, and these were temporally delayed (p<0.001) and much smaller in volume (P≤0.012) compared to KET and PEN animals. 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. Ketamine-xylazine and pentobarbital anesthesia can be reliably and effectively used to create models for the study of autoresuscitation in adult rats. In contrast, urethane causes catastrophic failure of respiratory autoresuscitation, by delaying or outright preventing the elaboration of gasping breaths following anoxia-induced respiratory arrest. The neuronal and synaptic alterations accompanying urethane anesthesia may therefore provide a means of understanding potential pathological alterations in rhythm generation that can predispose the respiratory control system to failed autoresuscitation following an episode of acute severe hypoxemia.

Hypocapnia-dependent facilitation of augmented breaths: observations in awake vs. anesthetized rats.

We investigated whether commonly used injectable laboratory anesthetics alter the regulation of augmented breaths (ABs) in different respiratory backgrounds. Male rats were studied on three separate experimental days, receiving one of three injections in randomized order: ethyl carbamate ('urethane'; 1.2mgkg(-1)), ketamine/xylazine (ket/xyl; 80/10mgkg(-1)), or normal saline. Following each of the three interventions, breathing was monitored during 15min exposures to normoxia (room air), hypoxia (10% O(2)) and hypoxia+CO(2) (10% O(2), 5% CO(2)). Urethane anesthesia completely eliminated ABs from the breathing rhythm in room air conditions (p<0.001), and decreased the hypocapnia-dependent component of this response (p<0.001). ket/xyl left the normal incidence of ABs in room air breathing intact but significantly suppressed the hypoxia-induced facilitation of ABs (p=0.0015). These results provide the first clear evidence that laboratory anesthesia can profoundly alter the regulation of ABs including the hypocapnia-dependent component of their facilitation.