ROLE OF K-ATP(+) CHANNELS IN DIAPHRAGMATIC FATIGUE IN THE PIG

We infused cromakalim, a K-ATP(+)-sensitive channel opener (80 mu g/kg as a bolus, followed by 1 mu g/kg/min, drop by drop infusion) into 15 anaesthetised, mechanically ventilated, indomethacin-treated pigs. In six of these animals, 120 min after hypotension had been evoked by cr omakalim, glibenclamide (10 mg/kg), a K-ATP(+)-sensitive channel antag onist, was administered i.v. over 5 min. The vascular variables and th e fatigue of the diaphragm evaluated as Pdi obtained during stimulus s trength and endurance test were recorded 120 min after hypotension (co ntrol time) and 5, 10, 20 and 30 min later. Cromakalim that induced a stable systemic hypotension did not modify diaphragmatic activity. Gli benclamide decline the transdiaphragmatic pressure during contractions of the diaphragm obtained with different frequencies of phrenic nerve stimulation and changed the response in the endurance test. Glibencla mide changes the Pdi(max) and half-relaxation time of a single contrac tion obtained immediately after the endurance test. Glibenclamide reve rsed the hypotensive effects of cromakalim. Our data indicate that K-A TP(+)-sensitive channels are involved in diaphragmatic activity and ar e important in delaying the appearance of fatigue.