Effects of almitrine on hypoglossal and phrenic electroneurograms

Almitrine increases breathing by stimulating peripheral chemoreceptors. Previous studies suggest clinical usefulness in the adult with chronic obstructive pulmonary disease, but little data are available to decide whether almitrine would be helpful in diseases involving pharyngeal airway obstruction, such as apnea of prematurity or obstructive sleep apnea. We investigated the effect of intravenous almitrine on hypoglossal (HG), an upper airway nerve, and phrenic (PHR) neural activity in eight α-chloralose-urethan anesthetized, paralyzed, vagotomized, and artificially ventilated cats. Recordings were made of raw and integrated HG and PHR electroneurograms (ENGs), alveolar PCO₂, arterial PO₂, arterial blood pressure, and rectal temperature. A dose-response study of cumulative almitrine doses ranging from 0.1 to 4.0 mg/kg was performed in three cats. The interactive effects of almitrine and hypoxic stimulation were investigated in four cats. The interactive effects of almitrine and hypercapnic stimulation were investigated in five cats. The interactive effects of almitrine and ventilatory timing were investigated in six cats. We found that almitrine doses as low as 0.1 mg/kg iv increased both HG and PHR ENG activity, with a maximum effect at ~ 1.0 mg/kg; almitrine markedly increased HG and PHR ENG activity at all arterial PO₂ values from 35-175 Torr; almitrine increased HG and PHR ENG activity at all arterial PCO₂ values from 30-70 Torr; and almitrine increased the ratio of tidal volume to inspiratory time and decreased the inspiratory muscle duty cycle at normoxia and eucapnia.