Ultrastructure of Type-I Cell Mitochondria in the Rat Carotid Body Following Chronic Oral Administration of Almitrine Bismesylate

Abstract

Almitrine bismesylate causes a marked and prolonged excitation of peripheral arterial chemoreceptors, especially those present in the carotid bodies (Laubie and Schmitt, 1980; O’Regan et al., 1983). Effects of this agent on blood gases and pulmonary function have been studied in normal human subjects, patients with chronic obstructive pulmonary disease (COPD), and a variety of animals. In COPD patients, almitrine, administered orally, induces a small elevation in minute ventilation in association with rises in Pao₂ levels and reductions in Paco₂ values (see Howard, 1989). These observations indicate that almitrine augments peripheral arterial chemoreceptor response to hypoxaemia (Stradling et al., 1984). The changes in Pao₂ and Paco₂ following almitrine administration have also been attributed to the increases in tidal volume with little or no overall change in ventilation (Dull et al., 1983). On the other hand, almitrine has been shown to enhance hypoxic vasoconstriction of the pulmonary vasculature (Romaldini et al., 1982; Melot et al., 1983) inducing as a consequence a reduction in ventilation-perfusion inequality in the lung. This latter effect could also aid in improving arterial blood gas status in COPD, but its importance in the genesis of this improvement relative to changes in ventilation is debatable (Tweney, 1987). In this context it has been reported that an intact nerve supply to carotid chemoreceptors is necessary for increases in Pa02 values to almitrine administration in animals (Dhillon and Barer, 1982) and man (de Backer et al., 1985). In the treatment of COPD almitrine is preferred to other respiratory stimulants owing to fewer side effects. One side effect of almitrine, however, is the development of peripheral neuropathies. Hypoxaemia itself appears to be the main aetiological factor in the production of these neuropathies in COPD, but almitrine administration renders more obviously their clinical manifestations for reasons as yet unknown (Howard, 1989).