nonassociative learning promotes respiratory entrainment to mechanical ventilation非联合型学习促进呼吸道夹带机械通风.pdfVIP

Nonassociative Learning Promotes Respiratory Entrainment to Mechanical Ventilation Shawna M. MacDonald., Gang Song., Chi-Sang Poon* Harvard-Massachusetts Institute of Technology Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America Background. Patient-ventilator synchrony is a major concern in critical care and is influenced by phasic lung-volume feedback control of the respiratory rhythm. Routine clinical application of positive end-expiratory pressure (PEEP) introduces a tonic input which, if unopposed, might disrupt respiratory-ventilator entrainment through sustained activation of the vagally- mediated Hering-Breuer reflex. We suggest that this potential adverse effect may be averted by two differentiator forms of nonassociative learning (habituation and desensitization) of the Hering-Breuer reflex via pontomedullary pathways. Methodology/Principal Findings. We tested these hypotheses in 17 urethane-anesthetized adult Sprague-Dawley rats under controlled mechanical ventilation. Without PEEP, phrenic discharge was entrained 1:1 to the ventilator rhythm. Application of PEEP momentarily dampened the entrainment to higher ratios but this effect was gradually adapted by nonassociative learning. Bilateral electrolytic lesions of the pneumotaxic center weakened the adaptation to PEEP, whereas sustained stimulation of the pneumotaxic center weakened the entrainment independent of PEEP. In all cases, entrainment was abolished after vagotomy. Conclusions/Significance. Our results demonstrate an important functional role for pneumotaxic desensitization and extra-pontine habituation of the Hering-Breuer reflex elicited by lung inflation: