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GAL‐160 Preferentially Increases Respiratory Motor Drive to the Tongue over the Diaphragm during Unobstructed Breathing and Standardized Obstructive Apneas (OA) in Rats
Author(s) -
Baby S,
Mardirosian S,
Schemm C,
Peng S,
Golder F,
MacIntyre E
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.1013.6
Subject(s) - medicine , diaphragm (acoustics) , respiratory system , anesthesia , denervation , breathing , respiratory rate , airway , cardiology , chemistry , heart rate , physics , acoustics , loudspeaker , blood pressure
GAL‐160, a carotid body (CB) stimulant, decreases spontaneous OA frequency and OA duration in a rodent model of OSA. Mechanistically, we propose that the effect of GAL‐160 on OA frequency is due to increased upper airway respiratory muscle (RM UA ) activity during eupnea, and the effect of GAL‐160 on OA duration is due to an increased response of RM UA to obstruction. We evaluated the effects of GAL‐160 on eupneic respiratory drive to the RM UA by recording hypoglossal (HN) and phrenic (PN) neurograms from urethane anesthetized, mechanically ventilated rats before and during IV infusion of vehicle and GAL‐160 (0.24 mg/kg over 30‐min). Baseline neurograms were standardized between rats by setting baseline P aCO 2 at 3 mmHg above each animal's apneic threshold to CO 2 . To evaluate the effects of GAL‐160 on the RM UA response to obstruction, the EMG GG and EMG DIA responses to standardized 10‐s tracheal obstructions were recorded from anesthetized, spontaneously breathing rats, before and during GAL‐160/vehicle infusions. GAL‐160 increased HN activity (67 ± 23% above baseline) without altering PN activity (‐13 ± 20%) during unobstructed breathing. Bilateral CB denervation abolished this effect. GAL‐160 increased the peak EMG GG response to a 10‐s obstruction (pre‐drug: 214 ± 180%; GAL‐160: 589 ± 358%; p <0.01) without altering the EMG DIA response (pre‐drug: 60 ± 31%; GAL‐160: 78 ± 47%). Vehicle infusion had no effect on the neurograms or EMGs recorded. These data demonstrate that GAL‐160 preferentially increases respiratory drive to the RM UA via the CB and during both eupneic breathing and OA. This mechanism may contribute to the efficacy of GAL‐160 in our rodent model of spontaneous OSA.