The goal of this study was to examine the effects of systemic morphine on the pattern and morphology of gasping breathing during respiratory autoresuscitation from transient anoxia. We hypothesized that systemic morphine levels sufficient to cause significant depression of eupnea, would also cause depression of gasping breathing. Respiratory and cardiovascular variables were studied in twenty spontaneously breathing, pentobarbital-anaesthetized adult male rats. Sham (saline) injections caused no significant change in resting respiratory or cardiovascular variables (n=10). Morphine, on the other hand, caused significant depression of eupneic breathing, with ventilation and peak inspiratory flow decreased by ~30 to 60%, depending on the background condition (n=10). In contrast, morphine did not affect depress gasping breathing. Duration of primary apnea, time to restore eupnea, the number and amplitude of gasping breaths, average and maximum peak flows and volume of gasping breaths were not significantly different post-injection in either condition. Blood pressures were all significantly lower following morphine injection at key time points in the process of autoresuscitation. Lastly, rate of successful recovery from anoxia was 80% in the morphine group (8/10) compared to 100% (10/10) in the sham group, post-injection. We conclude that the mechanisms and/or anatomic correlates underlying generation of gasping rhythm are distinct from those underlying eupnea, allowing gasping to remain robust to systemic morphine levels causing significant depression of eupnea. Morphine nevertheless decreases likelihood of recovery from transient anoxia, possibly as a result of decreased tissue perfusion pressures at critical time points during the process of respiratory autoresuscitation.
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.
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