Nonassociative Learning Promotes Respiratory Entrainment to Mechanical Ventilation 英文参考文献.docVIP

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Nonassociative Learning Promotes Respiratory Entrainment to Mechanical Ventilation 英文参考文献.doc

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Nonassociative Learning Promotes Respiratory Entrainment to Mechanical Ventilation 英文参考文献

NonassociativeLearningPromotesRespiratory EntrainmenttoMechanicalVentilation ShawnaM.MacDonald.,GangSong.,Chi-SangPoon* Harvard-Massachusetts Institute of Technology Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, Massachusetts,UnitedStatesofAmerica Background.Patient-ventilatorsynchronyisamajorconcernincriticalcareandisinfluencedbyphasiclung-volumefeedback 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- mediatedHering-Breuerreflex.Wesuggestthatthispotentialadverseeffectmaybeavertedbytwodifferentiatorformsof 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. Bilateralelectrolytic lesions ofthe pneumotaxic center weakenedthe adaptationtoPEEP,whereas sustainedstimulationofthepneumotaxiccenterweakenedtheentrainmentindependentofPEEP.Inallcases,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: acting as buffers or high-pass filters against tonic vagal volume input, these differentiator forms of nonassociative learning help to restorerespiratory-ventilatorentrainmentinthefaceofPEEP.Suchcentralsites-specifichabituationanddesensitizationofthe Hering-Breuer reflex provide a useful experimental model of nonassociative lea