Isoflurane facilitates hiccup-like reflex through gamma aminobutyric acid (GABA)A- and suppresses through GABAB-receptors in pentobarbital-anesthetized cats.

Abstract

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. Isoflurane facilitated the hiccup-like reflex through activation of central and peripheral gamma aminobutyric acid (GABA)(A) receptors but suppressed it via activation of central and peripheral GABA(B) receptors. The net result was that the hiccup-like reflex was inhibited in proportion to the alveolar isoflurane concentration.