Abstract
We previously demonstrated dose-dependent increases in both hypoglossal and phrenic electroneurograms after almitrine in anesthetized, paralyzed, and vagotomized cats. We have now investigated the effect of this peripheral chemoreceptor stimulant on diaphragmatic and genioglossal (GG, an upper airway-maintaining muscle) electromyograms in five unanesthetized, chronically instrumented, spontaneously breathing adult cats during slow-wave sleep. In 12 studies almitrine doses of 1.0-6.0 mg/kg increased inspired minute ventilation (VI), frequency (f), and tidal volume (VT) and decreased expiratory time (TE). However, almitrine doses as high as 6.0 mg/kg failed to augment phasic inspiratory GG activity. To determine why almitrine induced phasic inspiratory upper airway activity in anesthetized, vagotomized cats but not in sleeping cats, additional studies were performed. In four dose-response studies in three pentobarbital-anesthetized cats, almitrine, 1.0-6.0 mg/kg, did not produce phasic inspiratory GG activity. Almitrine did induce phasic inspiratory GG activity in two of three studies in three vagotomized, tracheostomized, alpha-chloralose-urethan-anesthetized cats. These results suggest that almitrine would not be useful in obstructive sleep apnea, yet because almitrine markedly increased VI, f, and VT and decreased TE in unanesthetized sleeping cats the drug may be effective in patients who lack normal central neural respiratory drive, such as the preterm infant. We previously demonstrated dose-dependent increases in both hypoglossal and phrenic electroneurograms after almitrine in anesthetized, paralyzed, and vagotomized cats. We have now investigated the effect of this peripheral chemoreceptor stimulant on diaphragmatic and genioglossal (GG, an upper airway-maintaining muscle) electromyograms in five unanesthetized, chronically instrumented, spontaneously breathing adult cats during slow-wave sleep. In 12 studies almitrine doses of 1.0-6.0 mg/kg increased inspired minute ventilation (VI), frequency (f), and tidal volume (VT) and decreased expiratory time (TE). However, almitrine doses as high as 6.0 mg/kg failed to augment phasic inspiratory GG activity. To determine why almitrine induced phasic inspiratory upper airway activity in anesthetized, vagotomized cats but not in sleeping cats, additional studies were performed. In four dose-response studies in three pentobarbital-anesthetized cats, almitrine, 1.0-6.0 mg/kg, did not produce phasic inspiratory GG activity. Almitrine did induce phasic inspiratory GG activity in two of three studies in three vagotomized, tracheostomized, alpha-chloralose-urethan-anesthetized cats. These results suggest that almitrine would not be useful in obstructive sleep apnea, yet because almitrine markedly increased VI, f, and VT and decreased TE in unanesthetized sleeping cats the drug may be effective in patients who lack normal central neural respiratory drive, such as the preterm infant.
