Effect of Almitrine on Ventilation and on Diaphragm and Geniohyoid Muscle Activity in the Rat

Abstract

1. Ventilation was measured during normoxia, hypoxia and hypercapnia before and after administration of almitrine in conscious, unrestrained, tracheostomized rats with the superior laryngeal nerves intact or cut. In superior laryngeal nerve-intact animals breathing air, almitrine increased minute ventilation due to an increase in respiratory frequency with no change in tidal volume. In superior laryngeal nerve-sectioned animals, the minute ventilatory response to almitrine was reduced due to a reduced tidal volume component of the response. Almitrine increased the ventilatory response to hypercapnia in superior laryngeal nerve-intact but not in sectioned animals. 2. In anaesthetized, vagotomized rats breathing spontaneously through a low-cervical tracheostomy, diaphragm and geniohyoid electromyographic activities were recorded. Arterial blood pressure and rectal temperature were continuously monitored. A single dose of almitrine was administered intravenously. In all animals, the geniohyoid muscle had phasic inspiratory activity which slightly preceded diaphragm activity. Almitrine had no effect on respiratory frequency or inspiratory and expiratory duration but increased mean peak integrated diaphragm (+29.3 ±13.6%) and geniohyoid (+ 132.0 ±21.3%) muscle activity. 3. These results show that almitrine exerts part of its ventilatory effects through superior laryngeal nerve afferents. Almitrine preferentially excites upper airway compared with diaphragm muscle activity, suggesting a potential role in the alleviation of obstructive apnoea.