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Chronic phenytoin treatment reduces rat carotid body chemosensory responses to acute hypoxia

dc.contributor.authorAlcayaga J.
dc.contributor.authorOyarce M.P.
dc.contributor.authorDel Rio R.
dc.date.accessioned2020-09-02T22:11:04Z
dc.date.available2020-09-02T22:11:04Z
dc.date.issued2016
dc.identifier10.1016/j.brainres.2016.08.027
dc.identifier.citation1649, , 38-43
dc.identifier.issn00068993
dc.identifier.urihttps://hdl.handle.net/20.500.12728/3510
dc.descriptionVentilation is peripherally controlled by afferent activity arising from the peripheral chemoreceptors. In the rat, chemosensory activity is conveyed to the central nervous system through axons of neurons located in the nodose-petrosal-jugular-complex. These neurons have distinct electrophysiological properties, including a persistent Na+ current. Acute blockade of this current with phenytoin and other anti-epileptic drugs reduces normoxic chemosensory activity and responses to acute hypoxia. However, because anti-epileptic therapy is prolonged and there is no information on the effects of chronic phenytoin treatment on peripheral chemosensory activity, we studied the effects of long-lasting phenytoin treatment (~25 days) on afferent chemosensory activity, on a wide range of oxygen inspiratory fractions. Osmotic pumps containing dissolved phenytoin (166 mg/mL) or vehicle (daily flow: 60 µL) were implanted subcutaneously in male adult Sprague Dawley rats. At the end of the treatment, the animals were anesthetized and carotid sinus nerve activity was recorded in vivo. Afferent chemosensory activity in normoxia was not significantly different between control (71.2±2.2 Hz) and phenytoin treated (95.4±2.1 Hz) rats. In contrast, carotid body chemosensory responses to acute hypoxic challenges were markedly reduced in phenytoin treated rats, specifically in the lowest part of the hypoxic range (control 133.5±18.0 Hz vs phenytoin treated 50.2±29.4, at 5% FIO2). Chronic phenytoin treatment severely impaired the chemosensory responses to acute hypoxia, suggesting that long-term phenytoin treatment in patients may result in a reduced peripheral respiratory drive together with a reduction in the respiratory responses to hypoxic challenges. © 2016 Elsevier B.V.
dc.language.isoen
dc.publisherElsevier B.V.
dc.subjectCarotid body
dc.subjectChemosensory activity
dc.subjectPeripheral ventilatory drive
dc.subjectPetrosal ganglion
dc.subjectPhenytoin
dc.subjectoxygen
dc.subjectphenytoin
dc.subjectacute disease
dc.subjectadult
dc.subjectanimal experiment
dc.subjectanimal model
dc.subjectArticle
dc.subjectbrain hypoxia
dc.subjectcarotid body
dc.subjectcontrolled study
dc.subjectdrug efficacy
dc.subjecthyperoxia
dc.subjectmale
dc.subjectnonhuman
dc.subjectosmotic pump
dc.subjectpriority journal
dc.subjectrat
dc.subjectsingle drug dose
dc.subjecttreatment response
dc.titleChronic phenytoin treatment reduces rat carotid body chemosensory responses to acute hypoxia
dc.typeArticle


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