The mechanism by which volatile
anesthetics exert inconsistent effects on
hiccups is unknown. We elicited a
hiccup-like reflex by mechanical stimulation of the dorsal epipharynx in mechanically ventilated cats. The magnitude of the
hiccup-like reflex was measured as the peak negative esophageal pressure (nPes) generated against an occluded airway. First, we examined the effects of different end-expiratory concentrations of
isoflurane on nPes. Second, we determined the effects of 1.0 minimum alveolar
anesthetic concentration of
isoflurane on nPes after a peripherally restricted
gamma aminobutyric acid (
GABA)(A)-receptor antagonist,
bicuculline methiodide (BM), a
GABA(B)-receptor antagonist,
CGP 35348, a peripherally restricted
GABA(B)-receptor antagonist,
CGP 54626, or saline had been administered IV. Third, BM,
CGP 35348, or artificial cerebrospinal fluid was administered intracisternally before 1.0 minimum alveolar
anesthetic concentration of
isoflurane exposure. During
isoflurane anesthesia, nPes was inversely proportional to the end-expiratory
isoflurane concentration. The rank order of nPes values obtained after IV
drug pretreatment and
isoflurane exposure was BM < saline < CGP54626 < CGP35348. After intracisternal
drug pretreatment and
isoflurane administration, the order of nPes was BM < artificial cerebrospinal fluid < CGP35348.
Isoflurane modulates the
hiccup-like reflex in opposite directions through both central and peripheral
GABA(A) and
GABA(B) receptors, with the net effect being a dose-dependent suppression.
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