Absence of Gasping Breaths and Failure of Respiratory Autoresuscitation in Neonatal Rats Studied Under Ethyl Carbamate (Urethane) Anesthesia
Authors: Reed Joseph A , Bell Harold J 
Published: June 2021

Respiratory autoresuscitation is a well‐described process that facilitates recovery and survival following an acute exposure to a severe hypoxemic event. In adult rats, our laboratory has shown urethane anesthesia prevents autoresustitation and causes predictable cardiorespiratory collapse and sudden death as a result of even a single episode of severe hypoxemia. This effect was confirmed to be a direct consequence of failure to gasp and restore rhythmic breathing. Given these findings, we hypothesized that neonatal rats would also experience significant disruption of the respiratory autoresuscitation process, negatively impacting their survival from a severe hypoxemic event. To test our hypothesis, we studied 4 male and 5 female rat pups aged P11–13. Animals were divided into two experimental groups, defined by the anesthetic used to study animals. The urethane (URE, n=5, 3f/2m, 31±3g, 12.2±0.8 d) group was anesthetized with urethane (1.2 – 1.5 g/kg i.p.), and the ketamine‐xylazine (KET, n=4, 2f/2m, 35±5g, 13.0±0.8 d) group was anesthetized with ketamine‐xylazine (40/5 mg/kg i.p.). Animals were maintained at a rectal temperature of 35±0.3°C, equipped with a head cone to monitor breathing (VE) and ECG electrodes to monitor heart rate (HR). VE and HR were continuously monitored while breathing room air, and subsequently a mild hypoxic gas mixture (FiO2=0.10, balance N2). Following recovery, animals were monitored during exposure to acute severe hypoxemia (breathing 100% N2), access to normoxic air was restored (FiO2 = 0.21) once respiratory arrest occurred, and opportunity for spontaneous respiratory autoresuscitation was provided. Pending successful autoresuscitation, animals were allowed to recover to baseline, and received another exposure to severe hypoxemia. This was repeated up to 4 times before the animal was exposed to terminal asphyxia for purposes of euthanasia. Baseline VE (16.0±4.1 vs 19.2±10.0 mL/min), HR (357±18 vs. 308±79 bpm) were not different between URE and KET animals, nor were VE or HR during steady‐state in mild hypoxia. During exposures to severe hypoxemia, the interval between the onset of exposure and respiratory arrest were not different between conditions (26.2±7.2 sec vs. 28.2±3.2 sec), but the amplitude of the peak ventilatory response during severe hypoxemia before respiratory arrest was significantly smaller in the URE vs KET condition (30.2±10.2 vs. 50.3±15.3 mL/min). All animals in the KET group successfully autoresuscitated from 4/4 exposures to severe hypoxemia. In the URE group, 0/5 animals successfully autoresuscitated and none expressed a single gasping breath following respiratory arrest. In neonatal rats, urethane anesthesia causes fatal disruption of respiratory autoresuscitation in response to a single acute exposure to severe hypoxemia, preventing gasping breaths and normal restoration of eupneic breathing. These results demonstrate that urethane provides a pharmacological model of sudden death in response to severe hypoxemia that is relevant to the neonatal stage of development.

Support or Funding Information

JAR was the recipient of a CMU COM Summer Research Scholars Award. Additional intramural funding provided to HJB through CMU COM and ORSP.

This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.